Sulfamethoxazole

General Notices
<image: "bp98-038/untwmf12.png"
C10H11N3O3 S 253.3 723-46-6
Sulfamethoxazole complies with the requirements of the 3rd edition of the European
Pharmacopoeia [!"#$ %hese requirements are reproduced after the headin& '(efinition' )elow$
!"tion an# u$e Antibacterial.
%&epa&ation$
Co-trimoxazole Injection
Co-trimoxazole Oral Ss!ension
"ae#iatric Co-trimoxazole Oral Ss!ension
Co-trimoxazole $ablets
%is!ersible Co-trimoxazole $ablets
"ae#iatric Co-trimoxazole $ablets
&'en sl!'amet'oxazole is !rescribe# or #eman#e#( Sl)amet'oxazole s'all be #is!ense# or
s!!lie#.
Ph Eur

%*+INI$ION
Sl)amet'oxazole contains not less t'an ,,.0 !er cent an# not more t'an t'e e-i.alent o) 101.0
!er cent o) /-amino-*-05-met'1l-3-isoxazol1l2benzenesl!'onami#e( calclate# 3it' re)erence to
t'e #rie# sbstance.
CHA4AC$*4S
A 3'ite or almost 3'ite( cr1stalline !o3#er( !racticall1 insolble in 3ater( )reel1 solble in acetone(
s!arin5l1 solble in alco'ol( sli5'tl1 solble in et'er. It #issol.es in #ilte soltions o) so#im
'1#roxi#e.
I%*N$I+ICA$ION
+irst identification, -. /$
Second identification, -. 0. ($
A. 6eltin5 !oint 02$2$!4 27 18,9C to 1:29C.
;. *xamine b1 in)rare# absor!tion s!ectro!'otometr1 02$2$24 2( com!arin5 3it' t'e s!ectrm
obtaine# 3it' sulfamethoxazole 01S.
C. *xamine t'e c'romato5rams obtaine# in t'e test )or relate# sbstances. $'e !rinci!al s!ot in t'e
c'romato5ram obtaine# 3it' test soltion 0b2 is similar in !osition an# size to t'e !rinci!al s!ot in
t'e c'romato5ram obtaine# 3it' re)erence soltion 0a2.
%. %issol.e abot 5 m5 in 10 ml o) !2 h3drochloric acid . %ilte 1 ml o) t'e soltion to 10 ml 3it'
water 1. $'e soltion( 3it'ot )rt'er aci#i)ication( 5i.es t'e reaction o) !rimar1 aromatic amines
02$3$! 2.
$*S$S
!ppea&an"e of $olution %issol.e 1.0 5 in a mixtre o) 5 ml o) dilute sodium h3droxide solution 1
an# 5 ml o) water 1. $'e soltion is not more intensel1 colore# t'an re)erence soltion <5( ;<5 or
G<5 02ethod 44. 2$2$2 2.
!"i#it' $o 1.25 5( )inel1 !o3#ere#( a## 25 ml o) water 1. Heat at :09C )or 5 min. Cool in ice#
3ater )or abot 15 min an# )ilter. $o 20 ml o) t'e )iltrate a## 0.1 ml o) )romoth3mol )lue solution 1!
. Not more t'an 0.3 ml o) $!2 sodium h3droxide is re-ire# to c'an5e t'e color o) t'e in#icator.
(elate# $ub$tan"e$ *xamine b1 t'in-la1er c'romato5ra!'1 02$2$27 2( sin5 silica &el 5+264 1 as
t'e coatin5 sbstance.
%est solution 7a8$ %issol.e 0.10 5 o) t'e sbstance to be examine# in 3 ml o) a mixtre o) 2 .olmes
o) concentrated ammonia 1 an# /= .olmes o) methanol 1 an# #ilte to 5 ml 3it' t'e same
mixtre o) sol.ents.
%est solution 7)8$ %ilte 1 ml o) test soltion 0a2 to 5 ml 3it' a mixtre o) 2 .olmes o) concentrated
ammonia 1 an# /= .olmes o) methanol 1.
1eference solution 7a8$ %issol.e 20 m5 o) sulfamethoxazole 01S in 3 ml o) a mixtre o) 2 .olmes
o) concentrated ammonia 1 an# /= .olmes o) methanol 1 an# #ilte to 5 ml 3it' t'e same
mixtre o) sol.ents.
1eference solution 7)8$ %ilte 1.25 ml o) test soltion 0b2 to 50 ml 3it' a mixtre o) 2 .olmes o)
concentrated ammonia 1 an# /= .olmes o) methanol 1.
A!!l1 se!aratel1 to t'e !late 5 l o) eac' soltion. %e.elo! o.er a !at' o) 15 cm sin5 a mixtre o)
3 .olmes o) dilute ammonia 1! ( 5 .olmes o) water 1( /0 .olmes o) nitromethane 1 an# 50
.olmes o) dioxan 1. %r1 t'e !late at 1009C to 1059C an# examine in ltra.iolet li5't at 25/ nm.
An1 s!ot in t'e c'romato5ram obtaine# 3it' test soltion 0a2( a!art )rom t'e !rinci!al s!ot( is not
more intense t'an t'e s!ot in t'e c'romato5ram obtaine# 3it' re)erence soltion 0b2 00.5 !er cent2.
)ea*' metal$ 02$4$" 2. 1.0 5 com!lies 3it' limit test % )or 'ea.1 metals 020 !!m2. "re!are t'e
stan#ar# sin5 2 ml o) lead standard solution 7! ppm P)8 1.
+o$$ on #&'ing 02$2$32 2. Not more t'an 0.5 !er cent( #etermine# on 1.000 5 b1 #r1in5 in an o.en
at 1009C to 1059C.
Sulphate# a$h 02$4$!4 2. Not more t'an 0.1 !er cent( #etermine# on 1.0 5.
ASSA<
Carr1 ot t'e assa1 o) !rimar1 aromatic amino-nitro5en 02$6$" 2( sin5 0.2000 5 #eterminin5 t'e
en#-!oint electrometricall1.
1 ml o) $!2 sodium nitrite is e-i.alent to 25.33 m5 o) C10H11N3O3 S.
S$O4AG*
Store in a 3ell-close# container( !rotecte# )rom li5't.
Ph Eur
,&imethop&im
General Notices
<image: "bp98-0-1/untwmf8..png"
C1/H1=N/O3 2,0.3 73"-7-6
%rimethoprim complies with the requirements of the 3rd edition of the European Pharmacopoeia
[6#$ %hese requirements are reproduced after the headin& '(efinition' )elow$
!"tion an# u$e Antibacterial.
%&epa&ation$
Co-trimoxazole Injection
Co-trimoxazole Oral Ss!ension
"ae#iatric Co-trimoxazole Oral Ss!ension
Co-trimoxazole $ablets
%is!ersible Co-trimoxazole $ablets
"ae#iatric Co-trimoxazole $ablets
$rimet'o!rim $ablets
Ph Eur

%*+INI$ION
$rimet'o!rim contains not less t'an ,=.5 !er cent an# not more t'an t'e e-i.alent o) 101.0 !er
cent o) 2(/-#iamino-5-03(/(5-trimet'ox1benz1l2!1rimi#ine( calclate# 3it' re)erence to t'e #rie#
sbstance.
CHA4AC$*4S
A 3'ite or 1ello3is'-3'ite !o3#er( .er1 sli5'tl1 solble in 3ater( sli5'tl1 solble in alco'ol(
!racticall1 insolble in et'er.
I%*N$I+ICA$ION
+irst identification, -. 0$
Second identification, -. /. ($
A. 6eltin5 !oint 02$2$!4 27 1,,9C to 2039C.
;. %issol.e 20 m5 in $!2 sodium h3droxide an# #ilte to 100.0 ml 3it' t'e same sol.ent. %ilte
1.0 ml o) t'is soltion to 10.0 ml 3it' $!2 sodium h3droxide . *xamine# bet3een 230 nm an# 350
nm 02$2$26 2( t'e soltion s'o3s a sin5le absor!tion maximm( at 2=: nm. $'e s!eci)ic absorbance
at t'e maximm is abot 2/5.
C. *xamine b1 in)rare# absor!tion s!ectro!'otometr1 02$2$24 2( com!arin5 3it' t'e s!ectrm
obtaine# 3it' trimethoprim 01S.
%. %issol.e abot 25 m5( 'eatin5 i) necessar1( in 5 ml o) $62 sulphuric acid an# a## 2 ml o) a
18 5>l soltion o) potassium perman&anate 1 in $!2 sodium h3droxide . Heat to boilin5 an# a## to
t'e 'ot soltion 0./ ml o) formaldeh3de 1. 6ix( a## 1 ml o) $62 sulphuric acid ( mix an# 'eat
a5ain to boilin5. Cool an# )ilter. $o t'e )iltrate a## 2 ml o) chloroform 1 an# s'a?e .i5orosl1. $'e
c'loro)orm la1er( examine# in ltra.iolet li5't at 385 nm( s'o3s a 5reen )lorescence.
$*S$S
!ppea&an"e of $olution %issol.e 0.5 5 in 10 ml o) a mixtre o) 1 .olme o) water 1( /.5 .olmes
o) methanol 1 an# 5 .olmes o) chloroform 1. $'e soltion is not more intensel1 colore# t'an
re)erence soltion ;<: 02ethod 44. 2$2$2 2.
(elate# $ub$tan"e$ *xamine b1 t'in-la1er c'romato5ra!'1 02$2$27 2( sin5 silica &el 5+264 1 as
t'e coatin5 sbstance.
%est solution$ %issol.e 0.2 5 o) t'e sbstance to be examine# in a mixtre o) 1 .olme o) water 1(
/.5 .olmes o) methanol 1 an# 5 .olmes o) chloroform 1 an# #ilte to 5 ml 3it' t'e same
mixtre o) sol.ents.
1eference solution$ %ilte 1 ml o) t'e test soltion to 10 ml 3it' a mixtre o) 1 .olme o) water 1(
/.5 .olmes o) methanol 1 an# 5 .olmes o) chloroform 1. %ilte 1 ml o) t'is soltion to 50 ml 3it'
a mixtre o) 1 .olme o) water 1( /.5 .olmes o) methanol 1 an# 5 .olmes o) chloroform 1.
A!!l1 se!aratel1 to t'e !late 5 l o) eac' soltion. %e.elo! in a non-satrate# tan? o.er a !at' o)
1: cm sin5 a mixtre o) 2 .olmes o) anh3drous formic acid 1( 5 .olmes o) water 1. 10 .olmes
o) methanol 1 an# =5 .olmes o) eth3l acetate 1. %r1 t'e !late in a crrent o) col# air )or 5 min. At
t'e bottom o) a c'romato5ra!'1 tan? !lace an e.a!oratin5 #is' containin5 a mixtre o) 1 .olme o)
h3drochloric acid 1! ( 1 .olme o) water 1 an# 2 .olmes o) a 15 5>l soltion o) potassium
perman&anate 1( close t'e tan? an# allo3 to stan# )or 15 min. "lace t'e #rie# !late in t'e tan? an#
close t'e tan?. @ea.e t'e !late in contact 3it' t'e c'lorine .a!or )or 5 min. &it'#ra3 t'e !late an#
!lace it in a crrent o) col# air ntil t'e excess o) c'lorine is remo.e# an# an area o) t'e coatin5
belo3 t'e !oints o) a!!lication #oes not 5i.e a ble color 3it' a #ro! o) potassium iodide and
starch solution 1. S!ra1 3it' potassium iodide and starch solution 1. *xamine t'e !late in
ltra.iolet li5't at 25/ nm be)ore t'e treatment 3it' c'lorine an# in #a1li5't a)ter s!ra1in5. An1 s!ot
in t'e c'romato5ram obtaine# 3it' t'e test soltion( a!art )rom t'e !rinci!al s!ot( is not more
intense t'an t'e s!ot in t'e c'romato5ram obtaine# 3it' t'e re)erence soltion 00.2 !er cent2.
)ea*' metal$ 02$4$" 2. 2.0 5 com!lies 3it' limit test C )or 'ea.1 metals 020 !!m2. "re!are t'e
stan#ar# sin5 / ml o) lead standard solution 7! ppm P)8 1.
+o$$ on #&'in5 02$2$32 2. Not more t'an 1.0 !er cent( #etermine# on 1.00 5 b1 #r1in5 in an o.en at
1009C to 1059C.
Sulphate# a$h 02$4$!4 2. Not more t'an 0.1 !er cent( #etermine# on 1.0 5.
ASSA<
%issol.e 0.250 5 in 50 ml o) anh3drous acetic acid 1. $itrate 3it' $!2 perchloric acid #eterminin5
t'e en#-!oint !otentiometricall1 02$2$2 2.
1 ml o) $!2 perchloric acid is e-i.alent to 2,.03 m5 o) C1/H1=N/O3.
Ph Eur
/(!+ +01203S
General Notices
9ral :iquids compl3 with the requirements of the 3rd edition of the European Pharmacopoeia for
:iquids for oral use [672#$ %hese requirements are reproduced after the headin& '(efinition' )elow$
Ph Eur

%*+INI$ION
@i-i#s )or oral se are sall1 soltions( emlsions or ss!ensions containin5 one or more acti.e
in5re#ients in a sitable .e'icleA some li-i#s )or oral a#ministration ma1 consist o) li-i# acti.e
in5re#ients as sc'.
$'e1 are inten#e# to be s3allo3e# eit'er n#ilte# or a)ter #iltion. $'ese !re!arations ma1 also
be !re!are# be)ore se )rom concentrate# li-i# !re!arations( or )rom !o3#ers( 5ranles or tablets
)or t'e !re!aration o) oral soltions or ss!ensions sin5 a sitable .e'icle.
@i-i#s )or oral se ma1 contain sitable antimicrobial !reser.ati.es( antioxi#ants an# ot'er
exci!ients sc' as #is!ersin5( ss!en#in5( t'ic?enin5( emlsi)1in5( b))erin5( 3ettin5( solbilisin5(
stabilisin5( )la.orin5 an# s3eetenin5 a5ents an# colorin5 matter at'orise# b1 t'e com!etent
at'orit1.
*mlsions ma1 s'o3 e.i#ence o) !'ase se!aration bt are easil1 re)orme# on s'a?in5.
Ss!ensions ma1 s'o3 a se#iment 3'ic' is rea#il1 #is!erse# on s'a?in5 to 5i.e a ss!ension
3'ic' remains s))icientl1 stable to enable t'e correct #ose to be #eli.ere#.
@i-i#s )or oral se are s!!lie# in mlti#ose or sin5le-#ose containers. $'e1 are a#ministere#
eit'er in .olmes sc' as 5 ml or mlti!les t'ereo) or in small .olmes 0#ro!s2. *ac' #ose o) a
mlti#ose !re!aration is a#ministere# b1 means o) a #e.ice sitable )or measrin5 t'e !rescribe#
.olme.
&'ere a!!licable( containers )or li-i#s )or oral se com!l1 3it' t'e re-irements o) 2aterials ;sed
for the 2anufacture of 0ontainers 03$! an# sbsections2 an# 0ontainers 03$2 an# sbsections2.
"4O%BC$ION
%rin5 t'e #e.elo!ment o) a li-i# )or oral se( t'e )ormlation )or 3'ic' contains an antimicrobial
!reser.ati.e( t'e e))ecti.eness o) t'e c'osen !reser.ati.e s'all be #emonstrate# to t'e satis)action
o) t'e com!etent at'orit1. A sitable met'o# o) test to5et'er 3it' criteria )or j#5in5 t'e
!reser.ati.e !ro!erties o) t'e )ormlation are !ro.i#e# in t'e text on Efficac3 of -ntimicro)ial
Preser<ation 76$!$3 8$
In t'e man)actre( !ac?a5in5( stora5e an# #istribtion o) li-i#s )or oral se( sitable means are
ta?en to ensre t'eir microbial -alit1A recommen#ations on t'is as!ect are !ro.i#e# in t'e text on
2icro)ial =ualit3 of Pharmaceutical Preparations 76$!$4 2.
In t'e man)actre o) li-i#s )or oral se containin5 #is!erse# !articles measres are ta?en to
ensre a sitable an# controlle# !article size 3it' re5ar# to t'e inten#e# se.
$*S$S
2nifo&mit' of "ontent Bnless ot'er3ise !rescribe# or jsti)ie# an# at'orise#( sin5le-#ose li-i#s
t'at are ss!ensions com!l1 3it' t'e )ollo3in5 test. A)ter s'a?in5( em!t1 eac' container as
com!letel1 as !ossible an# carr1 ot t'e test on t'e in#i.i#al contents. $'e1 com!l1 3it' test ; )or
;niformit3 of 0ontent of Sin&le-dose Preparations 02$>$6 2.
2nifo&mit' of ma$$ Sin5le-#ose li-i#s t'at are soltions or emlsions com!l1 3it' t'e )ollo3in5
test7 3ei5' in#i.i#all1 t'e contents o) t3ent1 containers( em!tie# as com!letel1 as !ossible( an#
#etermine t'e a.era5e mass. Not more t'an t3o o) t'e in#i.i#al masses #e.iate b1 more t'an 10
!er cent )rom t'e a.era5e mass an# none #e.iates b1 more t'an 20 !er cent.
3o$e an# unifo&mit' of #o$e of o&al #&op$ Into a sitable( 5ra#ate# c1lin#er( intro#ce b1
means o) t'e #ro!!in5 #e.ice t'e nmber o) #ro!s sall1 !rescribe# )or one #ose or intro#ce b1
means o) t'e measrin5 #e.ice( t'e sall1 !rescribe# -antit1. $'e #ro!!in5 s!ee# #oes not
excee# t3o #ro!s !er secon#. &ei5' t'e li-i#( re!eat t'e a##ition( 3ei5' a5ain an# carr1 on
re!eatin5 t'e a##ition an# 3ei5'in5 ntil a total o) ten masses are obtaine#. No sin5le mass
#e.iates b1 more t'an 10 !er cent )rom t'e a.era5e mass. $'e total o) ten masses #oes not #i))er
b1 more t'an 15 !er cent )rom t'e nominal mass o) ten #oses. I) necessar1( measre t'e total
.olme o) ten #oses. $'e .olme #oes not #i))er b1 more t'an 15 !er cent )rom t'e nominal .olme
o) ten #oses.
S$O4AG*
Store in a 3ell-close# container.
@A;*@@ING
$'e label states7
C t'e name o) an1 a##e# antimicrobial !reser.ati.e(
C t'e label )or oral #ro!s incl#es a statement o) t'e nmber o) #ro!s !er millilitre o) !re!aration
or !er 5ram o) !re!aration i) t'e #ose is measre# in #ro!s.
%ow#e&$ an# 4&anule$ fo& /&al Solution$ an# Su$pen$ion$
%*+INI$ION
"o3#ers an# 5ranles )or t'e !re!aration o) soltions or ss!ensions )or oral se 5enerall1
con)orm to t'e #e)initions in t'e mono5ra!'s on 9ral Powders 7!!668 an# 5ranules 74>>8
res!ecti.el1. $'e1 ma1 contain exci!ients in !articlar to )acilitate #is!ersion or #issoltion an# to
!re.ent ca?in5.
A)ter #issoltion or ss!ension( t'e1 com!l1 3it' t'e re-irements )or oral soltions or oral
ss!ensions( as a!!ro!riate.
$*S$S
2nifo&mit' of "ontent 02$>$6 2. Bnless ot'er3ise !rescribe# or jsti)ie# an# at'orise#( sin5le-#ose
!o3#ers an# sin5le-#ose 5ranles 3it' a content o) acti.e in5re#ient less t'an 2 m5 or less t'an 2
!er cent o) t'e total mass com!l1 3it' t'e test ; )or ;niformit3 of 0ontent of Sin&le-dose
Preparations 02$>$6 2. I) t'e !re!aration 'as more t'an one acti.e in5re#ient( t'e re-irement
a!!lies onl1 to t'ose in5re#ients t'at corres!on# to t'e abo.e con#itions. $'e test is not re-ire#
)or mlti.itamin an# trace-element !re!arations.
2nifo&mit' of ma$$ 02$>$6 2. Sin5le-#ose !o3#ers an# sin5le-#ose 5ranles com!l1 3it' t'e test
)or ni)ormit1 o) mass o) sin5le-#ose !re!arations. I) t'e test )or ni)ormit1 o) content is !rescribe#
)or all t'e acti.e in5re#ients( t'e test )or ni)ormit1 o) mass is not re-ire#.
S$O4AG*
Store in a 3ell-close# container.
@A;*@@ING
$'e label states7
C t'e met'o# o) !re!aration o) t'e soltion or ss!ension(
C t'e con#itions an# t'e #ration o) stora5e a)ter constittion.
Ph Eur
/&al +i5ui#$ of the 6&iti$h %ha&ma"opoeia
4n addition to the a)o<e requirements of the European Pharmacopoeia. the followin& statements
appl3 to an3 elixir. linctus. mixture. oral drops. oral emulsion. oral solution or oral suspension. that is
the su)?ect of an indi<idual mono&raph in the /ritish Pharmacopoeia$
S3rups. defined )3 the separate mono&raph of that title. are not 9ral :iquids since the3 are not
intended to )e administered as such )ut are used as <ehicle in&redients for their fla<ourin& and
sweetenin& properties$
3efinition $'e .e'icle )or an1 !articlar Oral @i-i# s'ol# be c'osen 'a.in5 re5ar# to t'e natre
o) t'e acti.e in5re#ient or in5re#ients an# to !ro.i#e or5anole!tic c'aracteristics a!!ro!riate to t'e
inten#e# se o) t'e !re!aration.
Oral @i-i#s ot'er t'an Oral *mlsions ma1 be s!!lie# as li-i#s or !re!are# jst be)ore isse )or
se b1 #issol.in5 or #is!ersin5 5ranles or !o3#er in t'e li-i# state# on t'e label.
Sto&age Oral @i-i#s s'ol# be ?e!t in 3ell-close# containers.
+abelling $'e label states 012 t'e #ate a)ter 3'ic' t'e Oral @i-i# is not inten#e# to be se#A 022 t'e
con#itions n#er 3'ic' t'e Oral @i-i# s'ol# be store#A 032 )or Oral *mlsions( Oral Ss!ensions
an#( 3'ere a!!ro!riate( )or 6ixtres( t'at t'e bottle s'ol# be s'a?en be)ore se.
I) t'e Oral @i-i# is s!!lie# as 5ranles or !o3#er to be constitte# jst be)ore isse )or se t'e
label states 012 t'at t'e contents o) t'e container are 5ranles or !o3#er )or t'e !re!aration o) an
Oral @i-i#A 022 t'e stren5t' as t'e amont o) t'e acti.e in5re#ient in a sitable #ose-.olme o) t'e
constitte# !re!arationA 032 t'e #irections )or !re!arin5 t'e Oral @i-i# incl#in5 t'e natre an#
-antit1 o) li-i# to be se#.
7+080(S
3efinition *lixirs are clear( )la.ore# Oral @i-i#s containin5 one or more acti.e in5re#ients
#issol.e# in a .e'icle t'at sall1 contains a 'i5' !ro!ortion o) Scrose or a sitable !ol1'1#ric
alco'ol or alco'ols an# ma1 also contain *t'anol 0,8 !er cent2 or a %ilte *t'anol.
+09:,2S7S
3efinition @inctses are .iscos Oral @i-i#s t'at ma1 contain one or more acti.e in5re#ients in
soltion. $'e .e'icle sall1 contains a 'i5' !ro!ortion o) Scrose( ot'er s5ars or a sitable
!ol1'1#ric alco'ol or alco'ols. @inctses are inten#e# )or se in t'e treatment or relie) o) co5'( an#
are si!!e# an# s3allo3e# slo3l1 3it'ot t'e a##ition o) 3ater.
;08,2(7S
3efinition 6ixtres are Oral @i-i#s containin5 one or more acti.e in5re#ients #issol.e#(
ss!en#e# or #is!erse# in a sitable .e'icle. Ss!en#e# soli#s ma1 se!arate slo3l1 on stan#in5
bt are easil1 re#is!erse# on s'a?in5.
/(!+ 3(/%S
3efinition Oral %ro!s are Oral @i-i#s t'at are inten#e# to be a#ministere# in small .olmes 3it'
t'e ai# o) a sitable measrin5 #e.ice.
/(!+ 7;2+S0/9S
3efinition Oral *mlsions are Oral @i-i#s containin5 one or more acti.e in5re#ients. $'e1 are
stabilise# oil-in-3ater #is!ersions( eit'er or bot' !'ases o) 3'ic' ma1 contain #issol.e# soli#s.
Soli#s ma1 also be ss!en#e# in Oral *mlsions.
&'en isse# )or se( Oral *mlsions s'ol# be s!!lie# in 3i#e-mot'e# bottles.
7xtempo&aneou$ p&epa&ation In Oral *mlsions !re!are# accor#in5 to t'e )ormla an# #irections
5i.en )or *xtem!oraneos !re!aration( t'e -antit1 o) emlsi)1in5 a5ent s!eci)ie# in in#i.i#al
mono5ra!'s ma1 be re#ce# to 1iel# a !re!aration o) sitable consistenc1 !ro.i#e# t'at b1 so
#oin5 t'e stabilit1 o) t'e !re!aration is not a#.ersel1 a))ecte#.
/(!+ S/+2,0/9S
3efinition Oral Soltions are Oral @i-i#s containin5 one or more acti.e in5re#ients #issol.e# in a
sitable .e'icle.
/(!+ S2S%79S0/9S
3efinition Oral Ss!ensions are Oral @i-i#s containin5 one or more acti.e in5re#ients ss!en#e#
in a sitable .e'icle. Ss!en#e# soli#s ma1 slo3l1 se!arate on stan#in5 bt are easil1 re#is!erse#.
%he followin& oral liquids are the su)?ect of an indi<idual mono&raph in the /ritish Pharmacopoeia$
Elixirs
C'loral *lixir( "ae#iatric
*!'e#rine *lixir
"'enobarbital *lixir
"i!erazine Citrate *lixir
:inctuses
Co#eine @incts
Co#eine @incts( "ae#iatric
6et'a#one @incts
"'olco#ine @incts
"'olco#ine @incts( Stron5
Sim!le @incts
Sim!le @incts( "ae#iatric
S-ill @incts( O!iate
S-ill @incts( "ae#iatric O!iate
$ol @incts( "ae#iatric Com!on#
2ixtures
Ammonia an# I!ecacan'a 6ixtre
Ammonim C'lori#e 6ixtre
C'loral 6ixtre
Gentian 6ixtre( Aci#
Gentian 6ixtre( Al?aline
I!ecacan'a *metic 6ixtre( "ae#iatric
Daolin an# 6or!'ine 6ixtre
Daolin 6ixtre
6a5nesim Carbonate 6ixtre( Aromatic
6a5nesim H1#roxi#e 6ixtre
6a5nesim Sl!'ate 6ixtre
6a5nesim $risilicate 6ixtre
"otassim Citrate 6ixtre
9ral Emulsions
@i-i# "ara))in Oral *mlsion
@i-i# "ara))in an# 6a5nesim H1#roxi#e Oral *mlsion
9ral Solutions
Alimemazine Oral Soltion( "ae#iatric>$rime!razine Oral Soltion( "ae#iatric
Alimemazine Oral Soltion( Stron5 "ae#iatric> $rime!razine Oral Soltion( Stron5
"ae#iatric
Amanta#ine Oral Soltion
Atenolol Oral Soltion
;aclo)en Oral Soltion
;metani#e Oral Soltion
Calci)erol Oral Soltion
C'lor!'enamine Oral Soltion>C'lor!'eniramine Oral Soltion
C'lor!romazine Oral Soltion
Cimeti#ine Oral Soltion
Clemastine Oral Soltion
Clomet'iazole Oral Soltion
Cloxacillin Oral Soltion
Co-amilozi#e Oral Soltion
Co#eine "'os!'ate Oral Soltion
%iaze!am Oral Soltion
%ic1clo.erine Oral Soltion>%ic1clomine Oral Soltion
%i5oxin Oral Soltion( "ae#iatric
%i'1#roco#eine Oral Soltion
%i!'en'1#ramine Oral Soltion
*tami.an Oral Soltion
*t'osximi#e Oral Soltion
+erros Sl!'ate Oral Soltion( "ae#iatric
+lcloxacillin Oral Soltion
Halo!eri#ol Oral Soltion
Halo!eri#ol Oral Soltion( Stron5
Io#ine Oral Soltion( A-eos
6etoclo!rami#e Oral Soltion
Neom1cin Oral Soltion
Orci!renaline Oral Soltion
"aracetamol Oral Soltion( "ae#iatric
"'enox1met'1l!enicillin Oral Soltion
"roc'lor!erazine Oral Soltion
"romet'azine Oral Soltion
4aniti#ine Oral Soltion
So#im Eal!roate Oral Soltion
$emaze!am Oral Soltion
$'iori#azine Oral Soltion
$riclo)os Oral Soltion
9ral Suspensions
Aciclo.ir Oral Ss!ension
Alminim H1#roxi#e Oral Ss!ension
Amitri!t1line Oral Ss!ension
Amoxicillin Oral Ss!ension
Am!icillin Oral Ss!ension
;arim Sl!'ate Oral Ss!ension
;enorilate Oral Ss!ension
Ce)alexin Oral Ss!ension
Cimeti#ine Oral Ss!ension
Co-)lam!icil Oral Ss!ension
Co-ma5al#rox Oral Ss!ension
Co-trimoxazole Oral Ss!ension
Co-trimoxazole Oral Ss!ension( "ae#iatric
*r1t'rom1cin *t'1l Sccinate Oral Ss!ension
+erros +marate Oral Ss!ension
+lcloxacillin Oral Ss!ension
+si#ic Aci# Oral Ss!ension
Ib!ro)en Oral Ss!ension
6a5al#rate Oral Ss!ension
Nabmetone Oral Ss!ension
Nali#ixic Aci# Oral Ss!ension
Na!roxen Oral Ss!ension
Nitraze!am Oral Ss!ension
Nitro)rantoin Oral Ss!ension
N1statin Oral Ss!ension
"aracetamol Oral Ss!ension
"'en1toin Oral Ss!ension
"rimi#one Oral Ss!ension
4i)am!icin Oral Ss!ension
Sl)a#imi#ine Oral Ss!ension( "ae#iatric
$'iori#azine Oral Ss!ension
%!(79,7(!+ %(7%!(!,0/9S
General Notices
Parenteral Preparations compl3 with the requirements of the 3rd edition of the European
Pharmacopoeia [62#$ %hese requirements are reproduced after the headin& '(efinition' )elow$
Ph Eur
%he requirements of this mono&raph do not necessaril3 appl3 to products deri<ed from human
)lood. from immunolo&ical preparations. radiopharmaceutical preparations or to prostheses to )e
implanted$
%*+INI$ION
"arenteral !re!arations are sterile !re!arations inten#e# )or a#ministration b1 injection( in)sion or
im!lantation into t'e 'man or animal bo#1.
"arenteral !re!arations ma1 re-ire t'e se o) exci!ients( )or exam!le to ma?e t'e !re!aration
isotonic 3it' bloo#( to a#jst t'e !H( to increase solbilit1( to !re.ent #eterioration o) t'e acti.e
in5re#ients or to !ro.i#e a#e-ate antimicrobial !ro!erties bt not to a#.ersel1 a))ect t'e inten#e#
me#icinal action o) t'e !re!aration or( at t'e concentrations se#( to case toxicit1 or n#e local
irritation.
Containers )or !arenteral !re!arations are ma#e as )ar as !ossible )rom materials t'at are
s))icientl1 trans!arent to !ermit t'e .isal ins!ection o) t'e contents( exce!t )or im!lants an# in
ot'er jsti)ie# an# at'orise# cases.
&'ere a!!licable( t'e containers )or !arenteral !re!arations com!l1 3it' t'e re-irements )or
2aterials ;sed for the 2anufacture of 0ontainers 03$! an# sbsections2 an# 0ontainers 03$2 an#
sbsections2. "arenteral !re!arations are s!!lie# in 5lass containers 03$2$! 2 or in ot'er containers
sc' as !lastic containers 03$2$2 . 3$2 $7 and 3$2$> 2 an# !re)ille# s1rin5es com!l1in5 3it' t'e
re-irements o) t'e com!etent at'orit1. $'e ti5'tness o) t'e container is ensre# b1 sitable
means. Closres ensre a 5oo# seal( !re.ent t'e access o) micro-or5anisms an# ot'er
contaminants an# sall1 !ermit t'e 3it'#ra3al o) a !art or t'e 3'ole o) t'e contents 3it'ot
remo.al o) t'e closre. $'e !lastic materials or elastomers 03$2$> 2 o) 3'ic' t'e closre is
com!ose# are s))icientl1 )irm an# elastic to allo3 t'e !assa5e o) a nee#le 3it' t'e least !ossible
s'e##in5 o) !articles. Closres )or mlti#ose containers are s))icientl1 elastic to ensre t'at t'e
!nctre is reseale# 3'en t'e nee#le is 3it'#ra3n.
Se.eral cate5ories o) !arenteral !re!arations ma1 be #istin5is'e#7
C injections(
C intra.enos in)sions(
C concentrates )or injections or intra.enos in)sions(
C !o3#ers )or injections or intra.enos in)sions(
C im!lants.
"4O%BC$ION
%rin5 t'e #e.elo!ment o) a !arenteral !re!aration( t'e )ormlation )or 3'ic' contains an
antimicrobial !reser.ati.e( t'e e))ecti.eness o) t'e c'osen !reser.ati.e s'all be #emonstrate# to
t'e satis)action o) t'e com!etent at'orit1. A sitable met'o# o) test to5et'er 3it' criteria )or j#5in5
t'e !reser.ati.e !ro!erties o) t'e )ormlation are !ro.i#e# n#er Efficac3 of -ntimicro)ial
Preser<ation 06$!$3 2.
"arenteral !re!arations are !re!are# sin5 materials an# met'o#s #esi5ne# to ensre sterilit1 an#
to a.oi# t'e intro#ction o) contaminants an# t'e 5ro3t' o) micro-or5anismsA recommen#ations on
t'is as!ect are !ro.i#e# in t'e text on 2ethods of Preparation of Sterile Products 06$!$! 2.
&ater se# in t'e man)actre o) !arenteral !re!arations com!lies 3it' t'e re-irements o) 3ater
)or injections in bl? state# in t'e mono5ra!' on @ater for in?ections 7!6>8.
$*S$S
6a"te&ial en#otoxin$ 02$6$!4 2. $'e test )or bacterial en#otoxins ma1 re!lace t'e test )or !1ro5ens
in t'e )ollo3in5 circmstances7
C )or a !re!aration t'at is t'e sbject o) a mono5ra!' in t'e "'armaco!oeia( t'e test ma1 be
!rescribe# in t'e mono5ra!'(
C in an1 ot'er cases( t'e test con#itions an# t'e re-irements are to be at'orise# b1 t'e
com!etent at'orit1(
C 3'ere a test )or bacterial en#otoxins is !rescribe# or at'orise#( a test )or !1ro5ens is not
re-ire# nless jsti)ie# b1 s!ecial circmstances.
Ste&ilit' 02$6$! 2. "arenteral !re!arations com!l1 3it' t'e test )or sterilit1.
S$O4AG*
Store in a sterile( airti5't( tam!er-!roo) container.
@A;*@@ING
$'e label states t'e name an# concentration o) an1 a##e# antimicrobial !reser.ati.e.
0n<e"tion$
%*+INI$ION
Injections are sterile soltions( emlsions or ss!ensions. $'e1 are !re!are# b1 #issol.in5(
emlsi)1in5 or ss!en#in5 t'e acti.e in5re#ient an# an1 a##e# sbstances in @ater for in?ections
7!6>8( in a sitable( sterile non-a-eos li-i# or in a mixtre o) t'ese .e'icles.
Soltions )or injection( examine# n#er sitable con#itions o) .isibilit1( are clear an# !racticall1 )ree
)rom !articles.
*mlsions )or injection #o not s'o3 an1 e.i#ence o) !'ase se!aration. Ss!ensions )or injection
ma1 s'o3 a se#iment 3'ic' is rea#il1 #is!erse# on s'a?in5 to 5i.e a ss!ension 3'ic' remains
s))icientl1 stable to enable t'e correct #ose to be 3it'#ra3n.
Sin&le-dose preparations$ $'e .olme o) t'e injection in a sin5le-#ose container is s))icient to
!ermit t'e 3it'#ra3al an# a#ministration o) t'e nominal #ose sin5 a normal tec'ni-e.
2ultidose preparations. 6lti#ose a-eos injections contain a sitable antimicrobial !reser.ati.e
at an a!!ro!riate concentration exce!t 3'en t'e !re!aration itsel) 'as a#e-ate antimicrobial
!ro!erties. &'en it is necessar1 to !resent a !re!aration )or !arenteral se in a mlti#ose
container( t'e !recations to be ta?en )or its a#ministration an# more !articlarl1 )or its stora5e
bet3een sccessi.e 3it'#ra3als are 5i.en.
-ntimicro)ial preser<ati<es$ A-eos !re!arations 3'ic' are !re!are# sin5 ase!tic !recations
an# 3'ic' cannot be terminall1 sterilise# ma1 contain a sitable antimicrobial !reser.ati.e in an
a!!ro!riate concentration.
No antimicrobial !reser.ati.e is a##e# 3'en7
C t'e .olme to be injecte# in a sin5le #ose excee#s 15 ml( nless ot'er3ise jsti)ie#(
C t'e !re!aration is inten#e# )or a#ministration b1 rotes 3'ere( )or me#ical reasons( an
antimicrobial !reser.ati.e is not acce!table( sc' as intracisternall1 or b1 an1 rote 5i.in5 access to
t'e cerebros!inal )li#( or intra-or retro-oclarl1.
Sc' !re!arations are !resente# in sin5le-#ose containers.
"4O%BC$ION
In t'e man)actre o) injections containin5 #is!erse# !articles measres are ta?en to ensre a
sitable an# controlle# !articles size 3it' re5ar# to t'e inten#e# se.
$*S$S
2nifo&mit' of "ontent 02$>$6 2. Bnless ot'er3ise !rescribe# or jsti)ie# an# at'orise#( sin5le-#ose
ss!ensions )or injection 3it' a content o) acti.e in5re#ient less t'an 2 m5 or less t'an 2 !er cent o)
t'e total mass com!l1 3it' test A )or ni)ormit1 o) content o) sin5le-#ose !re!arations. I) t'e
!re!aration 'as more t'an one acti.e in5re#ient( t'e re-irement a!!lies onl1 to t'ose in5re#ients
t'at corres!on# to t'e abo.e con#itions. $'e test is not re-ire# )or mlti.itamin an# trace-element
!re!arations.
%'&ogen$ 02$6$" 2. &'en t'e .olme to be injecte# in a sin5le #ose is 15 ml or more( an# no test )or
bacterial en#otoxins is !rescribe# or at'orise#( t'e !re!aration com!lies 3it' t'e test )or !1ro5ens(
nless ot'er3ise jsti)ie# an# at'orise#. &'en t'e .olme to be injecte# in a sin5le #ose is less
t'an 15 ml( t'e label states t'at t'e !re!aration is !1ro5en-)ree an# no test )or bacterial en#otoxins
is !rescribe# or at'orise#( t'e !re!aration com!lies 3it' t'e test )or !1ro5ens.
0nt&a*enou$ 0nfu$ion$
%*+INI$ION
Intra.enos in)sions are sterile( a-eos soltions or emlsions 3it' 3ater as t'e continos
!'aseA t'e1 are )ree )rom !1ro5ens an# are sall1 ma#e isotonic 3it' bloo#. $'e1 are !rinci!all1
inten#e# )or a#ministration in lar5e .olme. Intra.enos in)sions #o not contain an1 a##e#
antimicrobial !reser.ati.e.
Soltions )or intra.enos in)sion( examine# n#er sitable con#itions o) .isibilit1( are clear an#
!racticall1 )ree )rom !articles.
*mlsions )or intra.enos in)sion #o not s'o3 an1 e.i#ence o) !'ase se!aration.
"4O%BC$ION
In t'e man)actre o) intra.enos in)sions containin5 #is!erse# !articles measres are ta?en to
ensre a sitable an# controlle# !article size 3it' re5ar# to t'e inten#e# se.
$'e .olme o) t'e intra.enos in)sion in t'e container is s))icient to !ermit t'e 3it'#ra3al an#
a#ministration o) t'e nominal #ose sin5 a normal tec'ni-e 02$>$!7 2.
$*S$S
%'&ogen$ 02$6$" 2. &'en no test )or bacterial en#otoxins is !rescribe# or at'orise#( t'e1 com!l1
3it' t'e test )or !1ro5ens( nless ot'er3ise jsti)ie# an# at'orise#. Inject 10 ml !er ?ilo5ram o)
bo#1 mass into eac' rabbit( nless ot'er3ise jsti)ie# an# at'orise#.
:on"ent&ate$ fo& 0n<e"tion$ o& 0nt&a*enou$ 0nfu$ion$
%*+INI$ION
Concentrates )or injections or intra.enos in)sions are sterile soltions inten#e# )or injection or
in)sion a)ter #iltion. $'e1 are #ilte# to a !rescribe# .olme 3it' a !rescribe# li-i# be)ore
a#ministration. A)ter #iltion( t'e1 com!l1 3it' t'e re-irements )or injections or )or intra.enos
in)sions.
$*S$S
%'&ogen$ 02$6$" 2. &'en no test )or bacterial en#otoxins is !rescribe# or at'orise#( t'e1 com!l1
3it' t'e test )or !1ro5ens !rescribe# )or injections or )or !arenteral in)sions( as a!!ro!riate( a)ter
#iltion to a sitable .olme.
%ow#e&$ fo& 0n<e"tion$ o& 0nt&a*enou$ 0nfu$ion$
%*+INI$ION
"o3#ers )or injections or intra.enos in)sions are soli#( sterile sbstances #istribte# in t'eir )inal
containers an# 3'ic'( 3'en s'a?en 3it' t'e !rescribe# .olme o) a !rescribe# sterile li-i#( ra!i#l1
)orm eit'er clear an# !racticall1 !article-)ree soltions or ni)orm ss!ensions. A)ter #issoltion or
ss!ension( t'e1 com!l1 3it' t'e re-irements )or injections or )or intra.enos in)sions.
+reeze-#rie# !ro#cts )or !arenteral se are consi#ere# as !o3#ers )or injections or intra.enos
in)sions.
$*S$S
2nifo&mit' of "ontent 02$>$6 2. Bnless ot'er3ise !rescribe# or jsti)ie# an# at'orise#( !o3#ers )or
injections or intra.enos in)sions 3it' a content o) acti.e in5re#ient less t'an 2 m5 or less t'an 2
!er cent o) t'e total mass or 3it' a nit mass e-al to or less t'an /0 m5 com!l1 3it' test A )or
ni)ormit1 o) content o) sin5le-#ose !re!arations. I) t'e !re!aration 'as more t'an one acti.e
in5re#ient( t'e re-irement a!!lies onl1 to t'ose in5re#ients t'at corres!on# to t'e abo.e
con#itions. $'e test is not re-ire# )or mlti.itamin an# trace-element !re!arations.
2nifo&mit' of ma$$ 02$>$6 2. "o3#ers )or injections or intra.enos in)sions com!l1 3it' t'e test )or
ni)ormit1 o) mass o) sin5le-#ose !re!arations. I) t'e test )or ni)ormit1 o) content is !rescribe# )or
all t'e acti.e in5re#ients( t'e test )or ni)ormit1 o) mass is not re-ire#.
%'&ogen$ 02$6$" 2. &'en no test )or bacterial en#otoxins is !rescribe# or at'orise#( t'e1 com!l1
3it' t'e test )or !1ro5ens !rescribe# )or injections or )or intra.enos in)sions( as a!!ro!riate( a)ter
#issoltion or ss!ension in a sitable .olme o) li-i#.
0mplant$
%*+INI$ION
Im!lants are sterile( soli# !re!arations o) a size an# s'a!e sitable )or !arenteral im!lantation an#
release t'e acti.e in5re#ients o.er an exten#e# !erio# o) time. $'e1 are !ro.i#e# in#i.i#all1 in
sterile containers.
Ph Eur
%a&ente&al %&epa&ation$ of the 6&iti$h %ha&ma"opoeia
4n addition to the a)o<e requirements of the European Pharmacopoeia. the followin& statements
appl3 to an3 in?ection. intra<enous infusion or implant that is the su)?ect of an indi<idual mono&raph
in the /ritish Pharmacopoeia$
3efinition %e)inition o) a !articlar "arenteral "re!aration as a soltion( emlsion or ss!ension in
&ater )or Injections #oes not !recl#e t'e inclsion o) sitable exci!ients 3'ere necessar1 )or t'e
!r!oses re)erre# to in t'e re-irements o) t'e *ro!ean "'armaco!oeia abo.e. In !articlar(
a-eos "arenteral "re!arations )or a#ministration b1 t'e sbctaneos( intra#ermal(
intramsclar( or( in t'e case o) lar5er .olmes( intra.enos rote( s'ol# i) !ossible be ma#e
isotonic 3it' bloo# b1 t'e a##ition o) So#im C'lori#e or ot'er sitable sbstances. Ho3e.er i)
b))erin5 a5ents are se# in !re!arations inten#e# )or intra-oclar or intracar#iac injection( or in
!re!arations t'at ma1 5ain access to t'e cerebros!inal )li#( 5reat care s'ol# be ta?en to ensre
t'at t'e natre an# concentration o) t'e c'osen a5ent are sitable )or t'e inten#e# rote o)
a#ministration.
&'ere t'e acti.e in5re#ient is ssce!tible to oxi#ati.e #e5ra#ation a!!ro!riate !recations( sc' as
t'e a##ition o) a sitable antioxi#ant or stora5e n#er ox15en-)ree nitro5en or ot'er sitable inert
5as( s'ol# be ta?en.
%&o#u"tion 6et'o#s o) sterilisation t'at ma1 be se# in t'e man)actre o) "arenteral
"re!arations are #escribe# in A!!en#ix FEIII .
&'ere a #irection is 5i.en to se &ater )or Injections in t'e man)actre o) a "arenteral
"re!aration( &ater )or Injections in bl? is se#. &'ere t'e se o) &ater )or Injections )ree )rom
#issol.e# air or &ater )or Injections )ree )rom #issol.e# carbon #ioxi#e is s!eci)ie#( 3ater )res'l1
!re!are# b1 t'e !rocess #escribe# n#er &ater )or Injections is boile# )or at least 10 mintes 3it'
as little ex!osre to air as !ossible( coole# 3it' !recations to excl#e air an# carbon #ioxi#e( an#
sterilise# b1 heatin& in an autocla<e.
%a&ti"ulate "ontamination &'ere state# in in#i.i#al mono5ra!'s( soltions to be injecte# t'at are
s!!lie# in containers 3it' a nominal content o) 100 ml or more com!l1 3it' t'e test )or su)-<isi)le
particles( A!!en#ix FIII A.
Sto&age Closres se# )or containers o) oil1 !arenteral !re!arations s'ol# be ma#e o) oil-resistant
materials.
+abelling &'ere a!!ro!riate t'e label states t'e stren5t' o) t'e !arenteral !re!aration in terms o)
t'e amont o) acti.e in5re#ient in a sitable #ose-.olme.
$'e label also states 012 t'e name o) an1 a##e# sbstanceA 022 t'e #ate a)ter 3'ic' t'e "arenteral
"re!aration is not inten#e# to be se#A 032 t'e con#itions n#er 3'ic' t'e "arenteral "re!aration
s'ol# be store#.
$'e label o) a sin5le-#ose !arenteral !re!aration states t'at an1 !ortion o) t'e contents remainin5
s'ol# be #iscar#e#.
09,(!=79/2S 09>2S0/9S
+abelling $'e label states t'e nominal .olme o) t'e contents.
%/?37(S >/( 09@7:,0/9S
2nifo&mit' of weight &'en re-ire# )or t'e Assa1 o) a !o3#er )or injection( #etermine t'e 3ei5't
o) t'e contents o) 10 containers as #escribe# in t'e test )or uniformit3 of wei&ht( A!!en#ix FII G .
+abelling $'e label states 012 t'at( 3'en #issol.e# or ss!en#e#( t'e contents o) t'e seale#
container are inten#e# )or !arenteral seA 022 t'e amont o) acti.e in5re#ient containe# in t'e
seale# containerA 032 t'e #irections )or t'e !re!aration o) t'e Injection or Intra.enos In)sion.
I) a container o) t'e li-i# )or constittin5 t'e !arenteral !re!aration is s!!lie# 3it' t'e !o3#er )or
injections( t'e label o) t'is container states t'e com!osition o) t'is li-i#.
:/9:79,(!,73 S/+2,0/9S >/( 09@7:,0/9S
+abelling $'e label states 012 t'e name o) t'e concentrate# soltionA 022 t'at t'e soltion mst be
#ilte# be)ore seA 032 t'e #irections )or t'e !re!aration o) t'e Injection or Intra.enos In)sion.
%he followin& parenteral preparations are the su)?ect of an indi<idual mono&raph in the /ritish
Pharmacopoeia$ %hose distin&uished )3 the s3m)ol in '4' in the list )elow are mono&raphs of the
European Pharmacopoeia$
4mplants
$estosterone Im!lants
4n?ections
Acet1lc1steine Injection
A#renaline Injection>*!ine!'rine Injection
A#renaline Injection 1 in 10(000( %ilte>*!ine!'rine Injection 1 in 10(000( %ilte
Amino!'1lline Injection
Amoxicillin Injection
Am!icillin Injection
A!rotinin Injection
Ascorbic Aci# Injection
Atenolol Injection
Atro!ine Injection
Azlocillin Injection
;enzatro!ine Injection
;enz1l!enicillin Injection
;etamet'asone Injection
;ret1lim Injection
;metani#e Injection
;!i.acaine Injection
;!i.acaine an# A#renaline Injection>;!i.acaine an# *!ine!'rine Injection
Calci)erol Injection
Calcitonin 0"or?2 Injection
Calcitonin 0Salmon2 Injection>Salcatonin Injection
Calcim Glconate Injection
Ca!reom1cin Injection
Carbenicillin Injection
Ce)azolin Injection
Ce)otaxime Injection
Ce)oxitin Injection
Ce)triaxone Injection
Ce)roxime Injection
C'loram!'enicol So#im Sccinate Injection
C'lormet'ine Injection>6stine Injection
C'loro-ine Sl!'ate Injection
C'lor!'enamine Injection>C'lor!'eniramine Injection
C'lor!romazine Injection
C'orionic Gona#otro!'in Injection
Cimeti#ine Injection
Cis!latin Injection
Clin#am1cin Injection
Clonaze!am Injection
Cloni#ine Injection
Cloxacillin Injection
Colistimet'ate Injection
C1anocobalamin Injection
C1clizine Injection
C1clo!'os!'ami#e Injection
C1tarabine Injection
%acarbazine Injection
%es)errioxamine Injection
%esmo!ressin Injection
%extromorami#e Injection
%iamor!'ine Injection
%iaze!am Injection
%iazoxi#e Injection
%i5oxin Injection
%i5oxin Injection( "ae#iatric
%i'1#roco#eine Injection
%imerca!rol Injection
%ino!rost Injection
%oxa!ram Injection
%oxorbicin Injection
%ro!eri#ol Injection
*#ro!'onim Injection
*r5ometrine Injection
*r5ometrine an# Ox1tocin Injection
*r5otamine Injection
*r1t'rom1cin *t'1l Sccinate Injection
*stra#iol Injection
*tami!'1lline Injection
*t'anolamine Oleate Injection
+lcloxacillin Injection
+lorescein Injection
+lororacil Injection
+l!ent'ixol Injection
+l!'enazine %ecanoate Injection
+rosemi#e Injection>+rsemi#e Injection
Gallamine Injection
Gentamicin Injection
Glca5on Injection
Gona#orelin Injection
Halo!eri#ol Injection
He!arin Injection
H1alroni#ase Injection
H1#ralazine Injection
H1#rocortisone Acetate Injection
H1#rocortisone So#im "'os!'ate Injection
H1#rocortisone So#im Sccinate Injection
H1#roxocobalamin Injection
H1#rox1!ro5esterone Injection
H1oscine ;t1lbromi#e Injection
H1oscine Injection
Inslin "re!arations I
;i!'asic Inslin Injection I
;i!'asic Iso!'ane Inslin Injection I
Inslin Injection I
Inslin Ginc Ss!ension I
Inslin Ginc Ss!ension 0Amor!'os2 I
Inslin Ginc Ss!ension 0Cr1stalline2 I
Iso!'ane Inslin Injection I
Inlin Injection
Io#ise# Oil +li# Injection
Io!'en#1late Injection
Iron %extran Injection
Iron Sorbitol Injection
Isoniazi# Injection
Iso!renaline Injection
Danam1cin Injection
Detamine Injection
@abetalol Injection
@i#ocaine Injection
@i#ocaine an# A#renaline Injection>@i#ocaine an# *!ine!'rine Injection
@oraze!am Injection
@1!ressin Injection I
6a5nesim Sl!'ate Injection
6e5lmine Ami#otrizoate Injection
6e5lmine Io#i!ami#e Injection
6e5lmine Iotalamate Injection
6el!'alan Injection
6ena#iol "'os!'ate Injection
6enotro!'in Injection
6e!tazinol Injection
6etaraminol Injection
6et'a#one Injection
6et'o'exital Injection
6et'otrexate Injection
6et'oxamine Injection
6et'1l#o!ate Injection
6et'1l!re#nisolone Acetate Injection
6etoclo!rami#e Injection
6eto!rolol Injection
6exiletine Injection
6i#azolam Injection
6or!'ine Sl!'ate Injection
6or!'ine an# Atro!ine Injection
Naloxone Injection
Naloxone Injection( Neonatal
Nan#rolone %ecanoate Injection
Nan#rolone "'en1l!ro!ionate Injection
Neosti5mine Injection
Ni?et'ami#e Injection
Nora#renaline Injection>Nore!ine!'rine Injection
Ox1tocin Injection
"ancronim Injection
"a!a.eretm Injection
"aral#e'1#e Injection
"enta5astrin Injection
"entami#ine Injection
"entazocine Injection
"et'i#ine Injection
"'enobarbital Injection
"'enol Injection( Oil1
"'enol an# Gl1cerol Injection
"'entolamine Injection
"'en1le!'rine Injection
"'en1toin Injection
"'1tomena#ione Injection
"otassim C'lori#e Concentrate( Sterile
"rilocaine Injection
"rocainami#e Injection
"rocaine ;enz1l!enicillin Injection>"rocaine "enicillin Injection
"rocaine ;enz1l!enicillin Injection( +orti)ie#>"rocaine "enicillin Injection( +orti)ie#
"roc'lor!erazine Injection
"roc1cli#ine Injection
"ro5esterone Injection
"romazine Injection
"romet'azine Injection
"ro!ranolol Injection
"ro!1lio#one Injection
"ro!1lio#one Oil1 Injection
"rotamine Sl!'ate Injection
"1ri#osti5mine Injection
4aniti#ine Injection
4ito#rine Injection
Salbtamol Injection
So#im Arot'iomalate Injection
So#im Ami#otrizoate Injection
So#im *tacr1nate Injection
So#im Io#i#e Injection
So#im Iotalamate Injection
So#im Stibo5lconate Injection
So#im $etra#ec1l Sl!'ate Injection
So#im $'iosl!'ate Injection
Somatro!in Injection Hincor!oratin5 Somatro!in +or Injection II
Sotalol Injection
S!ectinom1cin Injection
Stre!to?inase Injection
Stre!tom1cin Injection
Sl)a#iazine Injection
Sl)a#imi#ine Injection
Sxamet'onim C'lori#e Injection
$estosterone "ro!ionate Injection
$etracosacti#e Injection
$etracosacti#e Ginc Injection
$'iamine Injection
$'io!ental Injection
$'iote!a Injection
$obram1cin Injection
$ranexamic Aci# Injection
$riamcinolone Acetoni#e Injection
Bro)ollitro!in Injection
Eancom1cin Injection
Eera!amil Injection
Einblastine Injection
Eincristine Injection
Eitamins ; an# C Injection
Gclo!ent'ixol Acetate Injection
Gclo!ent'ixol %ecanoate Injection
4ntra<enous 4nfusions
Aciclo.ir Intra.enos In)sion
Amio#arone Intra.enos In)sion
Calcim C'lori#e Intra.enos In)sion
Ci!ro)loxacin Intra.enos In)sion
Clomet'iazole Intra.enos In)sion
Co-trimoxazole Intra.enos In)sion
%extran /0 Intra.enos In)sion
%extran :0 Intra.enos In)sion
%extran 110 Intra.enos In)sion
%iso#im "ami#ronate Intra.enos In)sion
%o!amine Intra.enos In)sion
*r1t'rom1cin @actobionate Intra.enos In)sion
+oscarnet Intra.enos In)sion
+rctose Intra.enos In)sion
Glcose Intra.enos In)sion
6annitol Intra.enos In)sion
6etroni#azole Intra.enos In)sion
"otassim C'lori#e an# Glcose Intra.enos In)sion
"otassim C'lori#e an# So#im C'lori#e Intra.enos In)sion
"otassim C'lori#e( So#im C'lori#e an# Glcose Intra.enos In)sion
So#im ;icarbonate Intra.enos In)sion
So#im Calcim *#etate Intra.enos In)sion
So#im C'lori#e an# Glcose Intra.enos In)sion
So#im C'lori#e Intra.enos In)sion
So#im @actate Intra.enos In)sion
So#im @actate Intra.enos In)sion( Com!on#
So#im Nitro!rssi#e Intra.enos In)sion
Sorbitol Intra.enos In)sion
$etrac1cline Intra.enos In)sion
$riso#im *#etate Intra.enos In)sion
,!6+7,S
General Notices
%a)lets compl3 with the requirements of the 3rd edition of the European Pharmacopoeia [47"#$
%hese requirements are reproduced after the headin& '(efinition' )elow$
Ph Eur
%he requirements of this mono&raph do not necessaril3 appl3 to preparations that are presented as
ta)lets intended for use other than )3 oral administration$ 1equirements for such preparations ma3
)e found. where appropriate. in other &eneral mono&raphs. for exampleA 1ectal preparations 7!!468
and Ba&inal preparations 7!!648$
%*+INI$ION
$ablets are soli# !re!arations eac' containin5 a sin5le #ose o) one or more acti.e in5re#ients an#
obtaine# b1 com!ressin5 ni)orm .olmes o) !articles. $'e1 are inten#e# )or oral a#ministration.
Some are s3allo3e# 3'ole( some a)ter bein5 c'e3e#( some are #issol.e# or #is!erse# in 3ater
be)ore bein5 a#ministere# an# some are retaine# in t'e mot' 3'ere t'e acti.e in5re#ient is
liberate#.
$'e !articles consist o) one or more acti.e in5re#ients 3it' or 3it'ot exci!ients sc' as #ilents(
bin#ers( #isinte5ratin5 a5ents( 5li#ants( lbricants( sbstances ca!able o) mo#i)1in5 t'e be'a.ior
o) t'e !re!arations in t'e #i5esti.e tract( colorin5 matter at'orise# b1 t'e com!etent at'orit1 an#
)la.orin5 sbstances.
$ablets are sall1 ri5't( circlar soli# c1lin#ers( t'e en# sr)aces o) 3'ic' are )lat or con.ex an#
t'e e#5es o) 3'ic' ma1 be be.elle#. $'e1 ma1 'a.e lines or brea?-mar?s an# ma1 bear a s1mbol
or ot'er mar?in5s. $ablets ma1 be coate#.
&'ere a!!licable( containers )or tablets com!l1 3it' t'e re-irements )or 2aterials used for the
manufacture of containers 03$! an# sbsections2 an# 0ontainers 03$2 an# sbsections2.
Se.eral cate5ories o) tablets )or oral se ma1 be #istin5is'e#7
C ncoate# tablets(
C coate# tablets(
C e))er.escent tablets(
C solble tablets(
C #is!ersible tablets(
C 5astro-resistant tablets(
C mo#i)ie#-release tablets(
C tablets )or se in t'e mot'.
"4O%BC$ION
$ablets are !re!are# b1 com!ressin5 ni)orm .olmes o) !articles or !article a55re5ates !ro#ce#
b1 5ranlation met'o#s. In t'e man)actre o) tablet cores( means are ta?en to ensre t'at t'e1
!ossess a sitable mec'anical stren5t' to resist 'an#lin5 3it'ot crmblin5 or brea?in5. $'is ma1
be #emonstrate# b1 examinin5 t'e +ria)ilit3 of uncoated ta)lets 02$>$7 2 an# t'e 1esistance to
crushin& 02$>$" 2. C'e3able tablets are !re!are# to ensre t'at t'e1 are easil1 crs'e# b1 c'e3in5.
In t'e man)actre( !ac?a5in5( stora5e an# #istribtion o) tablets( sitable means are ta?en to
ensre t'eir microbial -alit1A recommen#ations on t'is as!ect are !ro.i#e# in t'e text on
2icro)iolo&ical qualit3 of pharmaceutical preparations 06$!$4 2.
$*S$S
2nifo&mit' of "ontent 02$>$6 2. Bnless ot'er3ise !rescribe# or jsti)ie# an# at'orise#( tablets 3it'
a content o) acti.e in5re#ient less t'an 2 m5 or less t'an 2 !er cent o) t'e total mass com!l1 3it'
test A )or ni)ormit1 o) content o) sin5le-#ose !re!arations. I) t'e !re!aration 'as more t'an one
acti.e in5re#ient( t'e re-irement a!!lies onl1 to t'ose in5re#ients 3'ic' corres!on# to t'e abo.e
con#itions. $'e test is not re-ire# )or mlti.itamin an# trace-element !re!arations.
2nifo&mit' of ma$$ 02$>$6 2. Bncoate# tablets an#( nless ot'er3ise jsti)ie# an# at'orise#( )ilm-
coate# tablets com!l1 3it' t'e test )or ni)ormit1 o) mass o) sin5le-#ose !re!arations. I) t'e test )or
ni)ormit1 o) content is !rescribe# )or all t'e acti.e in5re#ients( t'e test )or ni)ormit1 o) mass is not
re-ire#.
3i$$olution. A sitable test ma1 be carrie# ot to #emonstrate t'e a!!ro!riate release o) t'e acti.e
in5re#ient0s2( )or exam!le one o) t'e tests #escribe# in (issolution test for solid dosa&e forms
02$>$3 2.
&'ere a #issoltion test is !rescribe#( a #isinte5ration test ma1 not be re-ire#.
S$O4AG*
Store in 3ell-close# container( !rotecte# )rom crs'in5 an# mec'anical s'oc?.
2n"oate# ,ablet$
%*+INI$ION
Bncoate# tablets incl#e sin5le-la1er tablets resltin5 )rom a sin5le com!ression o) !articles an#
mlti-la1er tablets consistin5 o) concentric or !arallel la1ers obtaine# b1 sccessi.e com!ression o)
!articles o) #i))erent com!osition. $'e exci!ients se# are not s!eci)icall1 inten#e# to mo#i)1 t'e
release o) t'e acti.e in5re#ient in t'e #i5esti.e )li#s.
Bncoate# tablets con)orm to t'e 5eneral #e)inition o) tablets. A bro?en section( 3'en examine#
n#er a lens( s'o3s eit'er a relati.el1 ni)orm textre 0sin5le-la1er tablets2 or a strati)ie# textre
0mlti-la1er tablets2 bt no si5ns o) coatin5.
$*S$S
3i$integ&ation. Bncoate# tablets com!l1 3it' t'e test )or #isinte5ration o) tablets an# ca!sles
02$>$! 2. Bse water 1 as t'e li-i#. A## a #isc to eac' tbe. O!erate t'e a!!arats )or 15 min(
nless ot'er3ise jsti)ie# an# at'orise#( an# examine t'e state o) t'e tablets. I) t'e tablets )ail to
com!l1 becase o) a#'erence to t'e #iscs( re!eat t'e test on a )rt'er six tablets omittin5 t'e #iscs.
$'e tablets com!l1 3it' t'e test i) all six 'a.e #isinte5rate#.
0hewa)le ta)lets are not required to compl3 with the test$
:oate# ,ablet$
%*+INI$ION
Coate# tablets are tablets co.ere# 3it' one or more la1ers o) mixtres o) .arios sbstances sc'
as natral or s1nt'etic resins( 5ms( 5elatin( inacti.e an# insolble )illers( s5ars( !lasticisers(
!ol1ols( 3axes( colorin5 matter at'orise# b1 t'e com!etent at'orit1 an# sometimes )la.orin5
sbstances an# acti.e in5re#ients. $'e sbstances se# as coatin5s are sall1 a!!lie# as a
soltion or ss!ension in con#itions in 3'ic' e.a!oration o) t'e .e'icle occrs. &'en t'e coatin5 is
a .er1 t'in !ol1meric coatin5( t'e tablets are ?no3n as )ilm-coate# tablets.
Coate# tablets 'a.e a smoot' sr)ace 3'ic' is o)ten colore# an# ma1 be !olis'e#A a bro?en
section( 3'en examine# n#er a lens( s'o3s a core srron#e# b1 one or more continos la1ers
3it' a #i))erent textre.
$*S$S
3i$integ&ation. Coate# tablets ot'er t'an )ilm-coate# tablets com!l1 3it' t'e test )or #isinte5ration
o) tablets an# ca!sles 02$>$! 2. Bse water 1 as t'e li-i#. A## a #isc to eac' tbe. O!erate t'e
a!!arats )or 80 min( nless ot'er3ise jsti)ie# an# at'orise#( an# examine t'e state o) t'e
tablets. I) an1 o) t'e tablets 'as not #isinte5rate#( re!eat t'e test on a )rt'er six tablets( re!lacin5
water 1 in t'e bea?er 3it' $!2 h3drochloric acid . $'e tablets com!l1 3it' t'e test i) all six 'a.e
#isinte5rate# in t'e aci# me#im.
+ilm-coate# tablets com!l1 3it' t'e #isinte5ration test !rescribe# )or ncoate# tablets exce!t t'at
t'e a!!arats is o!erate# )or 30 min( nless ot'er3ise jsti)ie# an# at'orise#.
I) coate# tablets or )ilm-coate# tablets )ail to com!l1 becase o) a#'erence to t'e #iscs( re!eat t'e
test on a )rt'er six tablets omittin5 t'e #iscs. $'e tablets com!l1 3it' t'e test i) all six 'a.e
#isinte5rate#.
0hewa)le coated ta)lets are not required to compl3 with the test.
7ffe&*e$"ent ,ablet$
%*+INI$ION
*))er.escent tablets are ncoate# tablets 5enerall1 containin5 aci# sbstances an# carbonates or
'1#ro5en carbonates 3'ic' react ra!i#l1 in t'e !resence o) 3ater to release carbon #ioxi#e. $'e1
are inten#e# to be #issol.e# or #is!erse# in 3ater be)ore a#ministration.
$*S$S
3i$integ&ation. "lace a tablet in a bea?er containin5 200 ml o) water 1 at 159C to 259CA nmeros
bbbles o) 5as are e.ol.e#. &'en t'e e.oltion o) 5as aron# t'e tablet or its )ra5ments ceases t'e
tablet 'as #isinte5rate#( bein5 eit'er #issol.e# or #is!erse# in t'e 3ater so t'at no a55lomerates o)
!articles remain. 4e!eat t'e o!eration on )i.e ot'er tablets. $'e tablets com!l1 3it' t'e test i) eac'
o) t'e six tablets se# #isinte5rates in t'e manner !rescribe# 3it'in 5 min( nless ot'er3ise jsti)ie#
an# at'orise#.
Soluble ,ablet$
%*+INI$ION
Solble tablets are ncoate# or )ilm-coate# tablets. $'e1 are inten#e# to be #issol.e# in 3ater
be)ore a#ministration. $'e soltion !ro#ce# ma1 be sli5'tl1 o!alescent #e to t'e a##e#
sbstances se# in t'e man)actre o) t'e tablets.
$*S$S
3i$integ&ation. Solble tablets #isinte5rate 3it'in 3 min 3'en examine# b1 t'e test )or
#isinte5ration o) tablets an# ca!sles 02$>$! 2( sin5 water 1 at 159C to 259C.
3i$pe&$ible ,ablet$
%*+INI$ION
%is!ersible tablets are ncoate# or )ilm-coate# tablets inten#e# to be #is!erse# in 3ater be)ore
a#ministration 5i.in5 a 'omo5eneos #is!ersion.
$*S$S
3i$integ&ation. %is!ersible tablets #isinte5rate 3it'in 3 min 3'en examine# b1 t'e test )or
#isinte5ration o) tablets an# ca!sles 02$>$! 2( sin5 water 1 at 159C to 259C.
>inene$$ of #i$pe&$ion. "lace t3o tablets in 100 ml o) water 1 an# stir ntil com!letel1 #is!erse#.
A smoot' #is!ersion is !ro#ce#( 3'ic' !asses t'ro5' a sie.e screen 3it' a nominal mes'
a!ertre o) :10 m.
4a$t&o-(e$i$tant ,ablet$
%*+INI$ION
Gastro-resistant tablets are mo#i)ie# release tablets t'at are inten#e# to resist t'e 5astric )li# an#
to release t'eir acti.e in5re#ient0s2 in t'e intestinal )li#. $'e1 are !re!are# b1 co.erin5 tablets 3it'
a 5astro-resistant coatin5 0enteric-coate# tablets2 or )rom 5ranles or !articles alrea#1 co.ere# 3it'
a 5astro-resistant coatin5.
$ablets co.ere# 3it' a 5astro-resistant coatin5 con)orm to t'e #e)inition o) coate# tablets.

"4O%BC$ION
+or tablets !re!are# )rom 5ranles or !articles alrea#1 co.ere# 3it' a 5astro-resistant coatin5( a
sitable test is carrie# ot to #emonstrate t'e a!!ro!riate release o) t'e acti.e in5re#ient0s2.
$*S$S
3i$integ&ation. +or tablets co.ere# 3it' a 5astro-resistant coatin5 carr1 ot t'e test )or
#isinte5ration 02$>$! 2 3it' t'e )ollo3in5 mo#i)ications. Bse 0.16 h3drochloric acid as t'e li-i#.
O!erate t'e a!!arats )or 2 '( or ot'er sc' time as ma1 be at'orise#( 3it'ot t'e #iscs an#
examine t'e state o) t'e tablets. $'e time o) resistance to t'e aci# me#im .aries accor#in5 to t'e
)ormlation o) t'e tablets to be examine#. It is t1!icall1 2 ' to 3 ' bt e.en 3it' at'orise#
#e.iations is not less t'an 1 '. No tablet s'o3s si5ns o) eit'er #isinte5ration 0a!art )rom )ra5ments
o) coatin52 or crac?s t'at 3ol# allo3 t'e esca!e o) t'e contents. 4e!lace t'e aci# b1 phosphate
)uffer solution pC 6$" 1 an# a## a #isc eac' tbe. O!erate t'e a!!arats )or 80 min an# examine
t'e state o) t'e tablets. I) t'e tablets )ail to com!l1 becase o) a#'erence to t'e #iscs( re!eat t'e
test on a )rt'er six tablets omittin5 t'e #iscs. $'e tablets com!l1 3it' t'e test i) all six 'a.e
#isinte5rate#.
;o#ifie#-(elea$e ,ablet$
%*+INI$ION
6o#i)ie#-release tablets are coate# or ncoate# tablets containin5 s!ecial exci!ients or !re!are# b1
s!ecial !roce#res 3'ic'( se!aratel1 or to5et'er( are #esi5ne# to mo#i)1 t'e rate or t'e !lace at
3'ic' t'e acti.e in5re#ient0s2 are release#.
"4O%BC$ION
A sitable test is carrie# ot to #emonstrate t'e a!!ro!riate release o) t'e acti.e in5re#ient0s2.
,ablet$ fo& 2$e in the ;outh
%*+INI$ION
$ablets )or se in t'e mot' are sall1 ncoate# tablets.
$'e1 are )ormlate# to e))ect a slo3 release an# local action o) t'e acti.e in5re#ient0s2 or t'e
release an# absor!tion o) t'e acti.e in5re#ient or in5re#ients at a #e)ine# !art o) t'e mot'.
Ph Eur
,ablet$ of the 6&iti$h %ha&ma"opoeia
4n addition to the a)o<e requirements of the European Pharmacopoeia. the followin& statements
appl3 to those ta)lets that are the su)?ect of an indi<idual mono&raph in the /ritish Pharmacopoeia$
3efinition Bnless ot'er3ise state# in t'e in#i.i#al mono5ra!'( tablets o) t'e ;ritis'
"'armaco!oeia are soli#( ri5't circlar c1lin#ers t'e en# sr)aces o) 3'ic' are )lat or con.ex an#
t'e e#5es o) 3'ic' ma1 be be.elle#.
$ablets o) t'e ;ritis' "'armaco!oeia ma1 contain )la.orin5 onl1 3'en in#icate# in t'e in#i.i#al
mono5ra!'.
$ablets t'at are t'e sbject o) in#i.i#al mono5ra!'s in t'e ;ritis' "'armaco!oeia ma1 be
ncoate#( com!ression-coate#( )ilm-coate# or s5ar-coate# nless ot'er3ise in#icate# in t'e
mono5ra!'. $ablets )or 3'ic' t'e mono5ra!' states J$'e1 are coate#J are com!ression-coate# or
)ilm-coate# or s5ar-coate#. $ablets ma1 be ma#e 5astro-resistant b1 enteric-coatin5 or b1 ot'er
means onl1 3'ere t'is is s!eci)icall1 in#icate# in t'e mono5ra!'. &'en !resente# as coate#
)ormlations it ma1 be necessar1 to remo.e t'e coatin5 be)ore !er)ormin5 t'e Assa1 an# tests
#escribe# in t'e mono5ra!'.
In !re!arin5 $ablets )or 3'ic' C'ocolate ;asis is s!eci)ie#( t'e acti.e in5re#ient ma1 be
incor!orate# 3it' a mixtre o) 15 !arts o) non-al?alinise# cocoa !o3#er o) commerce( 15 !arts o)
Scrose an# :0 !arts o) @actose.
:ontent of a"ti*e ing&e#ient of tablet$ $'e ran5e )or t'e content o) acti.e in5re#ient state# in t'e
mono5ra!' is base# on t'e re-irement t'at 20 tablets( or sc' ot'er nmber as ma1 be in#icate#
in t'e mono5ra!'( are se# in t'e Assa1. In circmstances 3'ere 20 tablets cannot be obtaine#( a
smaller nmber( 3'ic' mst not be less t'an )i.e( ma1 be se#( bt to allo3 )or sam!lin5 errors t'e
tolerances are 3i#ene# in accor#ance 3it' $able I.
,able 0 Kima5e7 Lb!,=-0/5>table1.!n5LM

$'e re-irements o) $able I a!!l1 3'en t'e state# limits are ,0 to 110N. +or limits ot'er t'an ,0 to
110N( !ro!ortionatel1 smaller or lar5er allo3ances s'ol# be ma#e.
3i$integ&ation +or t'ose Bncoate# or Coate# $ablets )or 3'ic' a re-irement )or %issoltion is
incl#e# in t'e in#i.i#al mono5ra!'( t'e re-irement )or %isinte5ration #oes not a!!l1.
2nifo&mit' of "ontent %etails o) t'e anal1tical met'o# to be em!lo1e# )or #eterminin5 t'e content
o) acti.e in5re#ient ma1 be incl#e# in certain mono5ra!'s. Bnless ot'er3ise state# in t'e
mono5ra!' t'e limits are as 5i.en in t'e test )or ;niformit3 of content( A!!en#ixFII H.
An1 tablets t'at 3'en examine# in#i.i#all1 s'o3 a 5ross #e.iation )rom t'e !rescribe# or state#
content are not o))icial.
+abelling $'e label states 012 t'e -antit1 o) t'e acti.e in5re#ient containe# in eac' tabletA 022
Jenteric-coate#J )or tablets coate# in t'is mannerA 032 t'e #ate a)ter 3'ic' t'e $ablets are not
inten#e# to be se#A 0/2 t'e con#itions n#er 3'ic' t'e $ablets s'ol# be store#.
%he followin& ta)lets are the su)?ect of an indi<idual mono&raph in the /ritish Pharmacopoeia$
Acenocomarol $ablets
Acetazolami#e $ablets
Aciclo.ir $ablets
Alimemazine $ablets>$rime!razine $ablets
Allo!rinol $ablets
Aloxi!rin $ablets
Alminim H1#roxi#e $ablets
Amilori#e $ablets
Amino!'1lline $ablets
Amio#arone $ablets
Amitri!t1line $ablets
Ascorbic Aci# $ablets
As!irin an# Ca))eine $ablets
As!irin $ablets
As!irin $ablets( %is!ersible
As!irin $ablets( *))er.escent Solble
Atenolol $ablets
Atro!ine $ablets
Aza!ro!azone $ablets
Azat'io!rine $ablets
;aclo)en $ablets
;en#ro)lmet'iazi#e $ablets>;en#ro)lazi#e $ablets
;enorilate $ablets
;enzatro!ine $ablets
;etamet'asone So#im "'os!'ate $ablets
;etamet'asone $ablets
;isaco#1l $ablets
;romocri!tine $ablets
;rom!'eniramine $ablets
;metani#e $ablets
;metani#e an# Slo3 "otassim $ablets
;sl)an $ablets
Calci)erol $ablets
Calcim Glconate $ablets
Calcim Glconate $ablets( *))er.escent
Calcim @actate $ablets
Ca!to!ril $ablets
Carbamaze!ine $ablets
Carbimazole $ablets
Cascara $ablets
Ce)roxime Axetil $ablets
Ce)alexin $ablets
C'lorambcil $ablets
C'lor#iaze!oxi#e H1#roc'lori#e $ablets
C'loro-ine "'os!'ate $ablets
C'loro-ine Sl!'ate $ablets
C'lorot'iazi#e $ablets
C'lor!'enamine $ablets>C'lor!'eniramine $ablets
C'lor!romazine $ablets
C'lor!ro!ami#e $ablets
C'lortali#one $ablets
C'oline $'eo!'1llinate $ablets
Cimeti#ine $ablets
Ci!ro)loxacin $ablets
Clemastine $ablets
Clomi)ene $ablets
Cloni#ine $ablets
Co-amilo)rse $ablets
Co-amilozi#e $ablets
Co-amoxicla. $ablets
Co-carel#o!a $ablets
Co-co#amol $ablets
Co-co#a!rin $ablets
Co-co#a!rin $ablets( %is!ersible
Co-#er5ocrine $ablets
Co-#1#ramol $ablets
Co-ma5al#rox $ablets
Co-!roxamol $ablets
Co-teni#one $ablets
Co-triamterzi#e $ablets
Co-trimoxazole $ablets
Co-trimoxazole $ablets( %i!ersible
Co-trimoxazole $ablets( "ae#iatric
Co#eine "'os!'ate $ablets
Colc'icine $ablets
Colistin $ablets
Cortisone $ablets
C1anocobalamin $ablets
C1clizine $ablets
C1clo!ent'iazi#e $ablets
C1clo!'os!'ami#e $ablets
C1!ro'e!ta#ine $ablets
%a!sone $ablets
%ebriso-ine $ablets
%esi!ramine $ablets
%examet'asone $ablets
%exam)etamine $ablets
%extromorami#e $ablets
%iaze!am $ablets
%iazoxi#e $ablets
%ic'loro!'en $ablets
%iclo)enac $ablets
%iclo)enac $ablets( Slo3
%ic1clo.erine $ablets>%ic1clomine $ablets
%iet'1lstilbestrol $ablets
%i)lnisal $ablets
%i5itoxin $ablets
%i5oxin $ablets
%i'1#roco#eine $ablets
%iloxani#e $ablets
%imen'1#rinate $ablets
%i!i!anone an# C1clizine $ablets
%i!1ri#amole $ablets
%isl)iram $ablets
%ocsate $ablets
%osle!in $ablets>%ot'ie!in $ablets
%ro!eri#ol $ablets
%1#ro5esterone $ablets
*!'e#rine H1#roc'lori#e $ablets
*r5ometrine $ablets
*r1t'rom1cin *t'1l Sccinate $ablets
*r1t'rom1cin Stearate $ablets
*r1t'rom1cin $ablets
*stro!i!ate $ablets
*tacr1nic Aci# $ablets
*t'ambtol $ablets
*t'in1lestra#iol $ablets
*t'1lestrenol $ablets
*to#olac $ablets
+enb)en $ablets
+eno!ro)en $ablets
+erros +marate an# +olic Aci# $ablets
+erros +marate $ablets
+erros Glconate $ablets
+erros Sl!'ate $ablets
+la.oxate $ablets
+lc1tosine $ablets
+l#rocortisone $ablets
+l!'enazine $ablets
+lrbi!ro)en $ablets
+l.oxamine $ablets
+olic Aci# $ablets
+rosemi#e $ablets>+rsemi#e $ablets
Gem)ibrozil $ablets
Glibenclami#e $ablets
Gliclazi#e $ablets
Gli!izi#e $ablets
Gli-i#one $ablets
Gl1cer1l $rinitrate $ablets
Griseo)l.in $ablets
Ganet'i#ine $ablets
Halo!eri#ol $ablets
H1#ralazine $ablets
H1#roc'lorot'iazi#e $ablets
H1#ro)lmet'iazi#e $ablets
H1#rotalcite $ablets
H1#rox1c'loro-ine $ablets
H1oscine ;t1lbromi#e $ablets
H1oscine $ablets
Ib!ro)en $ablets
Imi!ramine $ablets
In#oramin $ablets
Inositol Nicotinate $ablets
Io!anoic Aci# $ablets
Isoniazi# $ablets
Isosorbi#e %initrate $ablets
@abetalol $ablets
@e.o#o!a $ablets
@e.onor5estrel an# *t'in1lestra#iol $ablets
@e.ot'1roxine $ablets
@iot'1ronine $ablets
@it'im Carbonate $ablets
@it'im Carbonate $ablets( Slo3
@o!razolam $ablets
@oraze!am $ablets
@ormetaze!am $ablets
6a5nesim $risilicate $ablets( Com!on#
6ebe.erine $ablets
6e5estrol $ablets
6el!'alan $ablets
6ena#iol "'os!'ate $ablets
6e!tazinol $ablets
6e!1ramine $ablets
6erca!to!rine $ablets
6et)ormin $ablets
6et'a#one $ablets
6et'otrexate $ablets
6et'1lcelllose $ablets
6et'1l#o!a $ablets
6et'1l!re#nisolone $ablets
6et'1ser5i#e $ablets
6etoclo!rami#e $ablets
6eto!rolol $artrate $ablets
6etroni#azole $ablets
6ianserin $ablets
6inoc1cline $ablets
6itobronitol $ablets
6or!'ine $ablets
6oxis1l1te $ablets>$'1moxamine $ablets
Nabmetone $ablets
Nali#ixic Aci# $ablets
Na!roxen $ablets
Neom1cin $ablets
Neosti5mine $ablets
Niclosami#e $ablets
Nicotinami#e $ablets
Nicotinic Aci# $ablets
Nicotin1l Alco'ol $ablets
Nitraze!am $ablets
Nitro)rantoin $ablets
Noret'isterone $ablets
Nortri!t1line $ablets
N1statin $ablets
Orci!renaline $ablets
Or!'ena#rine H1#roc'lori#e $ablets
Oxaze!am $ablets
Ox!renolol $ablets
Ox1met'olone $ablets
Ox1tetrac1cline $ablets
"ancreatin $ablets
"aracetamol $ablets
"aracetamol $ablets( %is!ersible
"aracetamol $ablets( Solble
"enicillamine $ablets
"entaer1t'ritol $etranitrate $ablets
"entazocine $ablets
"entobarbital $ablets
"er!'enazine $ablets
"et'i#ine $ablets
"'enelzine $ablets
"'enin#amine $ablets
"'enin#ione $ablets
"'enobarbital So#im $ablets
"'enobarbital $ablets
"'enox1met'1l!enicillin $ablets
"'en1toin $ablets
"'1tomena#ione $ablets
"in#olol $ablets
"i!erazine "'os!'ate $ablets
"izoti)en $ablets
"ol#ine $ablets
"ol1t'iazi#e $ablets
"otassim C'lori#e $ablets( *))er.escent
"otassim C'lori#e $ablets( Slo3
"otassim Io#ate $ablets
"razosin $ablets
"re#nisolone $ablets
"re#nisolone $ablets( *nteric-coate#
"re#nisone $ablets
"rimi#one $ablets
"robeneci# $ablets
"rocainami#e $ablets
"roc'lor!erazine $ablets
"roc1cli#ine $ablets
"ro5anil $ablets
"romazine $ablets
"romet'azine H1#roc'lori#e $ablets
"romet'azine $eoclate $ablets
"ro!ant'eline $ablets
"ro!ranolol $ablets
"ro!1lt'ioracil $ablets
"rotri!t1line $ablets
"se#oe!'e#rine $ablets
"1razinami#e $ablets
"1ri#osti5mine $ablets
"1ri#oxine $ablets
"1rimet'amine $ablets
Oini#ine Sl!'ate $ablets
Oinine ;isl!'ate $ablets
Oinine Sl!'ate $ablets
4aniti#ine $ablets
4ito#rine $ablets
Salbtamol $ablets
Senna $ablets
So#im ;icarbonate $ablets( Com!on#
So#im C'lori#e $ablets
So#im Citrate $ablets
So#im Eal!roate $ablets
So#im Eal!roate $ablets( *nteric-coate#
Sotalol $ablets
S!ironolactone $ablets
Stanozolol $ablets
Slin#ac $ablets
Sl)a#imi#ine $ablets
Sl)in!1razone $ablets
$amoxi)en $ablets
$erbtaline $ablets
$etrac1cline $ablets
$'iamine $ablets
$'iori#azine $ablets
$iaben#azole $ablets
$imolol $ablets
$io5anine $ablets
$oco!'er1l Sccinate $ablets( Al!'a
$olazami#e $ablets
$olbtami#e $ablets
$ranexamic Aci# $ablets
$ran1lc1!romine $ablets
$riamcinolone $ablets
$ri)lo!erazine $ablets
$ri'ex1!'eni#1l $ablets>;enz'exol $ablets
$rimet'o!rim $ablets
$rimi!ramine $ablets
$ri!roli#ine $ablets
Eera!amil $ablets
Ei5abatrin $ablets
&ar)arin $ablets
Gclo!ent'ixol $ablets
:ozen&es
Am!'otericin @ozen5es
:o-t&imoxazole 0nt&a*enou$ 0nfu$ion
General Notices
$rimet'o!rim an# Sl)amet'oxazole Intra.enos In)sion
3efinition Co-trimoxazole Intra.enos In)sion is a sterile soltion containin5 $rimet'o!rim an# t'e
so#im #eri.ati.e o) Sl)amet'oxazole. It is !re!are# imme#iatel1 be)ore se b1 #iltin5 Sterile Co-
trimoxazole Concentrate 3it' bet3een 25 an# 35 times its .olme o) Glcose Intra.enos In)sion
or So#im C'lori#e Intra.enos In)sion.
%he intra<enous infusion complies with the requirements stated under Parenteral Preparations$
S,7(0+7 :/-,(0;/8!A/+7 :/9:79,(!,7
3efinition Sterile Co-trimoxazole Concentrate is a sterile soltion o) $rimet'o!rim an#
sl)amet'oxazole so#im( !re!are# b1 t'e interaction o) Sl)amet'oxazole an# So#im H1#roxi#e(
in t'e !ro!ortion 1 !art to 5 !arts( in &ater )or Injections containin5 /0 to /5N .>. o) "ro!1lene
Gl1col.
%he concentrate complies with the requirements for 0oncentrated Solutions for 4n?ections stated
under Parenteral Preparations and with the followin& requirements$
:ontent of t&imethop&imB :1-)189-/3 ,2.5 to 10:.5N o) t'e !rescribe# or state# amont o)
$rimet'o!rim.
:ontent of $ulfamethoxazoleB :10)1193/3 S ,2.5 to 10:.5N o) t'e !rescribe# or state# amont o)
Sl)amet'oxazole.
:ha&a"te&i$ti"$ A colorless or sli5'tl1 1ello3 soltion.
0#entifi"ation
A. A## #ro!3ise to :5 ml o) 0.16 h3drochloric acid a .olme o) t'e soltion containin5 0.= 5 o)
Sl)amet'oxazole( stirrin5 continosl1. Allo3 t'e ss!ension to stan# )or 5 mintes an# )ilter
t'ro5' a sintere#-5lass )ilter. &as' t'e resi#e 3it' 10 ml o) water ( recr1stallise )rom ethanol
7>6D8 an# #r1 at 1059. 4eser.e !art o) t'e resi#e )or test % an# #issol.e t'e remain#er in t'e
minimm .olme o) a 5N 3>. soltion o) sodium car)onate ( a## 16 h3drochloric acid #ro!3ise
ntil !reci!itation is com!lete( )ilter( 3as' t'e resi#e s!arin5l1 3it' water an# #r1 at 1059. $'e
infrared a)sorption spectrum o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e reference
spectrum o) sl)amet'oxazole .
;. $o a .olme containin5 =0 m5 o) $rimet'o!rim a## 30 ml o) 0.16 sodium h3droxide an# extract
3it' t3o 50-ml -antities o) chloroform . &as' t'e combine# extracts 3it' t3o 10-ml -antities o)
0.16 sodium h3droxide an# t'en 3it' 10 ml o) water ( s'a?e 3it' 5 5 o) anh3drous sodium
sulphate ( )ilter an# e.a!orate t'e )iltrate to #r1ness sin5 a rotar1 e.a!orator. $'e infrared
a)sorption spectrum o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e reference spectrum o)
trimet'o!rim .
C. Carr1 ot t'e met'o# )or thin-la3er chromato&raph3( A!!en#ix III A ( sin5 silica &el 5 as t'e
coatin5 sbstance an# a mixtre o) 100 .olmes o) chloroform ( 10 .olmes o) methanol an# 5
.olmes o) dimeth3lformamide as t'e mobile !'ase. A!!l1 se!aratel1 to t'e !late 5 l o) eac' o)
t'e )ollo3in5 soltions. +or soltion 012 e.a!orate to #r1ness a .olme o) t'e soltion containin5
0.18 5 o) Sl)amet'oxazole( s'a?e t'e resi#e 3it' = ml o) methanol an# )ilter. Soltion 022
contains 2.0N 3>. o) sulfamethoxazole /P01S in methanol . Soltion 032 contains 0./N 3>. o)
trimethoprim /P01S in methanol . A)ter remo.al o) t'e !late( allo3 it to #r1 in air an# s!ra1 3it'
dilute potassium iodo)ismuthate solution . One o) t'e !rinci!al s!ots in t'e c'romato5ram obtaine#
3it' soltion 012 corres!on#s to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 022 an# t'e
ot'er corres!on#s to t'at in t'e c'romato5ram obtaine# 3it' soltion 032.
!lCalinit' !H( ,.5 to 11.0( A!!en#ix E @ .
!$$a'
For trimethoprim $o a .olme containin5 /= m5 o) $rimet'o!rim a## 30 ml o) 0.16 sodium
h3droxide an# extract 3it' )or 50-ml -antities o) chloroform ( 3as'in5 eac' extract 3it' t'e same
t3o 10-ml -antities o) 0.16 sodium h3droxide . Combine t'e c'loro)orm extracts( extract 3it' )or
50-ml -antities o) 16 acetic acid ( 3as' t'e combine# extracts 3it' 5 ml o) chloroform an# #ilte
t'e a-eos extracts to 250 ml 3it' 16 acetic acid . $o 10 ml o) t'e resltin5 soltion a## 10 ml o)
16 acetic acid an# s))icient water to !ro#ce 100 ml an# measre t'e a)sor)ance o) t'e
resltin5 soltion at t'e maximm at 2:1 nm( A!!en#ix II ; . Calclate t'e content o) C1/H1=N/O3
ta?in5 20/ as t'e .ale o) A01N( 1 cm2 at t'e maximm at 2:1 nm.
For sulfamethoxazole $o a .olme o) t'e soltion containin5 0./ 5 o) Sl)amet'oxazole a## 80 ml
o) water an# 10 ml o) h3drochloric acid . A## 3 5 o) potassium )romide ( cool in ice an# titrate
slo3l1 3it' 0.16 sodium nitrite BS ( stirrin5 constantl1 an# #eterminin5 t'e en# !oint
electrometricall1. *ac' ml o) 0.16 sodium nitrite BS is e-i.alent to 25.33 m5 o) C10H11N3O3 S.
Sto&age Sterile Co-trimoxazole Concentrate s'ol# be !rotecte# )rom li5't.
+abelling $'e label states 012 JSterile Co-trimoxazole ConcentrateJA 022 t'e contents o) $rimet'o!rim
an# o) Sl)amet'oxazole in a sitable .olmeA 032 t'at t'e soltion s'ol# be !rotecte# )rom li5'tA
0/2 t'at t'e soltion mst be #ilte# 3it' bet3een 25 an# 35 times its .olme o) Glcose
Intra.enos In)sion or So#im C'lori#e Intra.enos In)sion imme#iatel1 be)ore seA 052 t'at t'e
Co-trimoxazole Intra.enos In)sion so !re!are# is to be a#ministere# intra.enosl1A 082 t'at t'e
intra.enos in)sion s'ol# be #iscar#e# i) an1 .isible !articles a!!ear.
:o-t&imoxazole /&al Su$pen$ion
General Notices
$rimet'o!rim an# Sl)amet'oxazole Oral Ss!ension
3efinition Co-trimoxazole Oral Ss!ension is a ss!ension containin5 1.8N 3>. o) $rimet'o!rim
an# =.0N 3>. o) Sl)amet'oxazole in a sitable )la.ore# .e'icle.
%he oral suspension complies with the requirements stated under 9ral :iquids and with the
followin& requirements$
:ontent of t&imethop&imB :1-)189-/3 1.// to 1.:8N 3>..
:ontent of $ulfamethoxazoleB :10)1193/3 S :./0 to =.80N 3>..
0#entifi"ation
A. $o a -antit1 containin5 50 m5 o) $rimet'o!rim a## 30 ml o) 0.16 sodium h3droxide an# extract
3it' )or 50-ml -antities o) chloroform . &as' t'e combine# extracts 3it' t3o 10-ml -antities o)
0.16 sodium h3droxide an# extract 3it' t3o 50-ml -antities o) chloroform . &as' t'e combine#
c'loro)orm extracts 3it' t3o 10-ml -antities o) 0.16 sodium h3droxide an# t'en 3it' 10 ml o)
water . S'a?e 3it' 5 5 o) anh3drous sodium sulphate ( )ilter an# e.a!orate to #r1ness sin5 a rotar1
e.a!orator. $'e infrared a)sorption spectrum o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e
reference spectrum o) trimet'o!rim .
;. Carr1 ot t'e met'o# )or thin-la3er chromato&raph3( A!!en#ix III A ( sin5 silica &el 5 as t'e
coatin5 sbstance an# a mixtre o) 100 .olmes o) chloroform ( 10 .olmes o) methanol an# 5
.olmes o) dimeth3lformamide as t'e mobile !'ase. A!!l1 se!aratel1 to t'e !late 5 l o) eac' o)
t'e )ollo3in5 soltions. +or soltion 012 a## 20 ml o) methanol to 5 ml o) t'e oral ss!ension( mix(
s'a?e 3it' 10 5 o) anh3drous sodium sulphate ( centri)5e an# se t'e s!ernatant li-i#. Soltion
022 contains 2.0N 3>. o) sulfamethoxazole /P01S in methanol . Soltion 032 contains 0./N 3>. o)
trimethoprim /P01S in methanol . A)ter remo.al o) t'e !late( allo3 it to #r1 in air an# s!ra1 3it'
dilute potassium iodo)ismuthate solution . One o) t'e !rinci!al s!ots in t'e c'romato5ram obtaine#
3it' soltion 012 corres!on#s to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 022 an# t'e
ot'er corres!on#s to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 032.
!"i#it' !H( 5.0 to 8.5( A!!en#ix E @ .
!$$a'
For trimethoprim *xtract t'e c'loro)orm soltion reser.e# in t'e Assa1 )or sl)amet'oxazole 3it'
)or 50-ml -antities o) 16 acetic acid . &as' t'e combine# extracts 3it' 5 ml o) chloroform an#
#ilte t'e a-eos extracts to 250 ml 3it' 16 acetic acid . $o 10 ml o) t'is soltion a## 10 ml o) 16
acetic acid an# s))icient water to !ro#ce 100 ml an# measre t'e a)sor)ance o) t'e resltin5
soltion at t'e maximm at 2:1 nm( A!!en#ix II ; . Calclate t'e content o) C1/H1=N/O3 ta?in5 20/
as t'e .ale o) A01N( 1 cm2 at t'e maximm at 2:1 nm. Bsin5 t'e 3ei5't !er ml o) t'e oral
ss!ension( calclate t'e content o) C1/H1=N/O3 ( 3ei5't in .olme.
For sulfamethoxazole $o / 5 o) t'e oral ss!ension a## 30 ml o) 0.16 sodium h3droxide ( s'a?e
an# extract 3it' )or 50-ml -antities o) chloroform ( 3as'in5 eac' extract 3it' t'e same t3o 10-ml
-antities o) 0.16 sodium h3droxide . 4eser.e t'e combine# c'loro)orm extracts )or t'e Assa1 )or
trimet'o!rim. %ilte t'e combine# a-eos soltion an# 3as'in5s to 250 ml 3it' water ( )ilter an#
#ilte 5 ml o) t'e )iltrate to 200 ml 3it' water 0soltion A2. Carr1 ot t'e )ollo3in5 !roce#re
!rotecte# )rom li5't sin5 2 ml o) soltion A. A## 0.5 ml o) /6 h3drochloric acid an# 1 ml o) a 0.1N
3>. soltion o) sodium nitrite an# allo3 to stan# )or 2 mintes. A## 1 ml o) a 0.5N 3>. soltion o)
ammonium sulphamate an# allo3 to stan# )or 3 mintes. A## 1 ml o) a 0.1N 3>. soltion o) N-7!-
naphth3l8eth3lenediamine dih3drochloride an# allo3 to stan# )or 10 mintes. %ilte t'e resltin5
soltion to 25 ml 3it' water an# measre t'e a)sor)ance at 53= nm( A!!en#ix II ; ( sin5 in t'e
re)erence cell a soltion !re!are# in t'e same manner bt sin5 2 ml o) water in !lace o) soltion
A. %issol.e 0.25 5 o) sulfamethoxazole /P01S in 50 ml o) 0.16 sodium h3droxide an# #ilte to
250 ml 3it' water . %ilte 5 ml o) t'e resltin5 soltion to 200 ml 3it' water 0soltion ;2. 4e!eat t'e
!roce#re sin5 2 ml o) soltion ; an# be5innin5 at t'e 3or#s JA## 0.5 ml o)...J. Calclate t'e
content o) C10H11N3O3 S )rom t'e .ales o) t'e absorbances obtaine#. %etermine t'e wei&ht per ml
o) t'e oral ss!ension( A!!en#ix E G ( an# calclate t'e content o) C10H11N3O3 S( 3ei5't in .olme.
Sto&age Co-trimoxazole Oral Ss!ension s'ol# be !rotecte# )rom li5't an# store# at a
tem!eratre not excee#in5 309.
Co-trimoxazole Oral Ss!ension contains( in 5 ml( =0 m5 o) $rimet'o!rim an# /00 m5 o)
Sl)amet'oxazole.
%ae#iat&i" :o-t&imoxazole /&al Su$pen$ion
General Notices
"ae#iatric $rimet'o!rim an# Sl)amet'oxazole Oral Ss!ension
3efinition "ae#iatric Co-trimoxazole Oral Ss!ension is a ss!ension containin5 0.=N 3>. o)
$rimet'o!rim an# /N 3>. o) Sl)amet'oxazole in a sitable )la.ore# .e'icle.
%he oral suspension complies with the requirements stated under 9ral :iquids and with the
followin& requirements$
:ontent of t&imethop&imB :1-)189-/3 0.:2 to 0.==N 3>..
:ontent of $ulfamethoxazoleB :10)1193/3 S 3.80 to /./0N 3>..
0#entifi"ation Com!lies 3it' t'e tests #escribe# n#er Co-trimoxazole Oral Ss!ension bt in test
; )or soltion 022 se a 1.0N 3>. soltion o) sulfamethoxazole /P01S in methanol an# )or soltion
032 se a 0.20N 3>. soltion o) trimethoprim /P01S in methanol . A!!l1 to t'e !late 10 l o) eac'
o) t'e t'ree soltions.
!"i#it' !H( 5.0 to 8.5( A!!en#ix E @ .
!$$a' Carr1 ot t'e Assa1s )or trimet'o!rim an# sl)amet'oxazole #escribe# n#er Co-trimoxazole
Oral Ss!ension bt sin5 = 5 o) t'e oral ss!ension.
Sto&age "ae#iatric Co-trimoxazole Oral Ss!ension s'ol# be !rotecte# )rom li5't an# store# at a
tem!eratre not excee#in5 309.
"ae#iatric Co-trimoxazole Oral Ss!ension contains( in 5 ml( /0 m5 o) $rimet'o!rim an# 200 m5 o)
Sl)amet'oxazole.
:o-t&imoxazole ,ablet$
General Notices
$rimet'o!rim an# Sl)amet'oxazole $ablets
3efinition Co-trimoxazole $ablets contain $rimet'o!rim an# Sl)amet'oxazole in t'e !ro!ortions(
b1 3ei5't( 1 !art to 5 !arts.
@ith the exception of the requirements for shape. the ta)lets compl3 with the requirements stated
under %a)lets and with the followin& requirements$
:ontent of t&imethop&imB :1-)189-/3 ,2.5 to 10:.5N o) t'e !rescribe# or state# amont o)
$rimet'o!rim.
:ontent of $ulfamethoxazoleB :10)1193/3 S ,2.5 to 10:.5N o) t'e !rescribe# or state# amont o)
Sl)amet'oxazole.
0#entifi"ation
A. +ilter t'e a-eos la1er reser.e# in t'e Assa1 )or trimet'o!rim. A##( #ro!3ise( s))icient 26
h3drochloric acid to t'e )iltrate to ma?e it jst aci#ic an# extract 3it' 50 ml o) ether . &as' t'e et'er
la1er 3it' 10 ml o) water ( s'a?e 3it' 5 5 o) anh3drous sodium sulphate ( )ilter an# e.a!orate t'e
)iltrate to #r1ness sin5 a rotar1 e.a!orator. %issol.e t'e resi#e in t'e minimm .olme o) a 5N
3>. soltion o) sodium car)onate ( a## 16 h3drochloric acid #ro!3ise ntil !reci!itation is com!lete
an# )ilter. &as' t'e resi#e s!arin5l1 3it' water an# #r1 at 1059. $'e infrared a)sorption spectrum
o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e reference spectrum o) sl)amet'oxazole .
;. $o a -antit1 o) t'e !o3#ere# tablets containin5 50 m5 o) $rimet'o!rim a## 30 ml o) 0.16
sodium h3droxide an# extract 3it' t3o 50-ml -antities o) chloroform . &as' t'e combine#
c'loro)orm extracts 3it' t3o 10-ml -antities o) 0.16 sodium h3droxide an# t'en 3it' 10 ml o)
water . S'a?e 3it' 5 5 o) anh3drous sodium sulphate ( )ilter an# e.a!orate to #r1ness sin5 a rotar1
e.a!orator. $'e infrared a)sorption spectrum o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e
reference spectrum o) trimet'o!rim .
C. Carr1 ot t'e met'o# )or thin-la3er chromato&raph3( A!!en#ix III A ( sin5 silica &el 5 as t'e
coatin5 sbstance an# a mixtre o) 100 .olmes o) chloroform ( 10 .olmes o) methanol an# 5
.olmes o) dimeth3lformamide as t'e mobile !'ase. A!!l1 se!aratel1 to t'e !late 5 l o) eac' o)
t'e )ollo3in5 soltions. +or soltion 012 s'a?e a -antit1 o) t'e !o3#ere# tablets containin5 0./ 5 o)
Sl)amet'oxazole 3it' 20 ml o) methanol an# )ilter. Soltion 022 contains 2.0N 3>. o)
sulfamethoxazole /P01S in methanol . Soltion 032 contains 0./N 3>. o) trimethoprim /P01S in
methanol . A)ter remo.al o) t'e !late( allo3 it to #r1 in air an# s!ra1 3it' dilute potassium
iodo)ismuthate solution . One o) t'e !rinci!al s!ots in t'e c'romato5ram obtaine# 3it' soltion 012
corres!on#s to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 022 an# t'e ot'er corres!on#s
to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 032.
!$$a'
For trimethoprim $o a -antit1 o) t'e !o3#er containin5 50 m5 o) $rimet'o!rim a## 30 ml o) 0.16
sodium h3droxide an# extract 3it' )or 50-ml -antities o) chloroform ( 3as'in5 eac' extract 3it'
t'e same t3o 10-ml -antities o) 0.16 sodium h3droxide . 4eser.e t'e a-eos la1er )or test A )or
I#enti)ication. Combine t'e c'loro)orm extracts an# extract 3it' )or 50-ml -antities o) 16 acetic
acid . &as' t'e combine# extracts 3it' 5 ml o) chloroform an# #ilte t'e a-eos extracts to 250
ml 3it' 16 acetic acid . $o 10 ml o) t'e soltion a## 10 ml o) 16 acetic acid an# s))icient water to
!ro#ce 100 ml an# measre t'e a)sor)ance o) t'e resltin5 soltion at t'e maximm at 2:1 nm(
A!!en#ix II ; . Calclate t'e content o) C1/H1=N/O3 ta?in5 20/ as t'e .ale o) A01N( 1 cm2 at t'e
maximm at 2:1 nm.
For sulfamethoxazole &ei5' an# !o3#er 20 tablets. %issol.e( as com!letel1 as !ossible( a
-antit1 o) t'e !o3#er containin5 0.5 5 o) Sl)amet'oxazole in 80 ml o) water an# 10 ml o)
h3drochloric acid . A## 3 5 o) potassium )romide ( cool in ice an# titrate slo3l1 3it' 0.16 sodium
nitrite BS ( stirrin5 constantl1 an# #eterminin5 t'e en# !oint electrometricall1. *ac' ml o) 0.16
sodium nitrite BS is e-i.alent to 25.33 m5 o) C10H11N3O3 S.
+abelling $'e label states t'e -antities o) $rimet'o!rim an# o) Sl)amet'oxazole in eac' tablet.
3i$pe&$ible :o-t&imoxazole ,ablet$
General Notices
%is!ersible $rimet'o!rim an# Sl)amet'oxazole $ablets
3efinition %is!ersible Co-trimoxazole $ablets contain $rimet'o!rim an# Sl)amet'oxazole an# in
t'e !ro!ortions( b1 3ei5't( 1 !art to 5 !arts in a sitable #is!ersible basis.
@ith the exception of the requirements for shape. the ta)lets compl3 with the requirements stated
under %a)lets and with the followin& requirements$
:ontent of t&imethop&imB :1-)189-/3 ,2.5 to 10:.5N o) t'e !rescribe# or state# amont o)
$rimet'o!rim.
:ontent of $ulfamethoxazoleB :10)1193/3 S ,2.5 to 10:.5N o) t'e !rescribe# or state# amont o)
Sl)amet'oxazole.
0#entifi"ation
A. +ilter t'e a-eos la1er reser.e# in t'e Assa1 )or trimet'o!rim. A##( #ro!3ise( s))icient 26
h3drochloric acid to t'e )iltrate to ma?e it jst aci#ic an# extract 3it' 50 ml o) ether . &as' t'e et'er
la1er 3it' 10 ml o) water ( s'a?e 3it' 5 5 o) anh3drous sodium sulphate ( )ilter an# e.a!orate t'e
)iltrate to #r1ness sin5 a rotar1 e.a!orator. %issol.e t'e resi#e in t'e minimm .olme o) a 5N
3>. soltion o) sodium car)onate ( a## 16 h3drochloric acid #ro!3ise ntil !reci!itation is com!lete
an# )ilter. &as' t'e resi#e s!arin5l1 3it' water an# #r1 at 1059. $'e infrared a)sorption spectrum
o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e reference spectrum o) sl)amet'oxazole .
;. $o a -antit1 o) t'e !o3#ere# tablets containin5 50 m5 o) $rimet'o!rim a## 30 ml o) 0.16
sodium h3droxide an# extract 3it' t3o 50-ml -antities o) chloroform . &as' t'e combine#
c'loro)orm extracts 3it' t3o 10-ml -antities o) 0.16 sodium h3droxide an# t'en 3it' 10 ml o)
water . S'a?e 3it' 5 5 o) anh3drous sodium sulphate ( )ilter an# e.a!orate to #r1ness sin5 a rotar1
e.a!orator. $'e infrared a)sorption spectrum o) t'e resi#e( A!!en#ix II A ( is concor#ant 3it' t'e
reference spectrum o) trimet'o!rim .
C. Carr1 ot t'e met'o# )or thin-la3er chromato&raph3( A!!en#ix III A ( sin5 silica &el 5 as t'e
coatin5 sbstance an# a mixtre o) 100 .olmes o) chloroform ( 10 .olmes o) methanol an# 5
.olmes o) dimeth3lformamide as t'e mobile !'ase. A!!l1 se!aratel1 to t'e !late 5 l o) eac' o)
t'e )ollo3in5 soltions. +or soltion 012 s'a?e a -antit1 o) t'e !o3#ere# tablets containin5 0./ 5 o)
Sl)amet'oxazole 3it' 20 ml o) methanol an# )ilter. Soltion 022 contains 2.0N 3>. o)
sulfamethoxazole /P01S in methanol . Soltion 032 contains 0./N 3>. o) trimethoprim /P01S in
methanol . A)ter remo.al o) t'e !late( allo3 it to #r1 in air an# s!ra1 3it' dilute potassium
iodo)ismuthate solution . One o) t'e !rinci!al s!ots in t'e c'romato5ram obtaine# 3it' soltion 012
corres!on#s to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 022 an# t'e ot'er corres!on#s
to t'e s!ot in t'e c'romato5ram obtaine# 3it' soltion 032.
3i$integ&ation $'e tablets #isinte5rate 3it'in 2 mintes 3'en examine# b1 t'e disinte&ration test
for ta)lets and capsules( A!!en#ix FII A ( bt sin5 water at 1,9 to 219.
!$$a'
For trimethoprim $o a -antit1 o) t'e !o3#er containin5 50 m5 o) $rimet'o!rim a## 30 ml o) 0.16
sodium h3droxide an# extract 3it' )or 50-ml -antities o) chloroform ( 3as'in5 eac' extract 3it'
t'e same t3o 10-ml -antities o) 0.16 sodium h3droxide . 4eser.e t'e a-eos la1er )or test A )or
I#enti)ication. Combine t'e c'loro)orm extracts an# extract 3it' )or 50-ml -antities o) 16 acetic
acid . &as' t'e combine# extracts 3it' )or 5-ml -antities o) chloroform an# #ilte t'e a-eos
extracts to 250 ml 3it' 16 acetic acid . $o 10 ml o) t'e soltion a## 10 ml o) 16 acetic acid an#
s))icient water to !ro#ce 100 ml an# measre t'e a)sor)ance o) t'e resltin5 soltion at t'e
maximm at 2:1 nm( A!!en#ix II ; . Calclate t'e content o) C1/H1=N/O3 ta?in5 20/ as t'e .ale o)
A01N( 1 cm2 at t'e maximm at 2:1 nm.
For sulfamethoxazole &ei5' an# !o3#er 20 tablets. %issol.e( as com!letel1 as !ossible( a
-antit1 o) t'e !o3#er containin5 0.5 5 o) Sl)amet'oxazole in 80 ml o) water an# 10 ml o)
h3drochloric acid . A## 3 5 o) potassium )romide ( cool in ice an# titrate slo3l1 3it' 0.16 sodium
nitrite BS ( stirrin5 constantl1 an# #eterminin5 t'e en# !oint electrometricall1. *ac' ml o) 0.16
sodium nitrite BS is e-i.alent to 25.33 m5 o) C10H11N3O3 S.
+abelling $'e label states 012 t'e -antities o) $rimet'o!rim an# o) Sl)amet'oxazole in eac'
tabletA 022 t'at t'e tablets s'ol# be #is!erse# in 3ater imme#iatel1 be)ore se.
%ae#iat&i" :o-t&imoxazole ,ablet$
General Notices
"ae#iatric $rimet'o!rim an# Sl)amet'oxazole $ablets
3efinition "ae#iatric Co-trimoxazole $ablets contain( in eac'( 20 m5 o) $rimet'o!rim an# 100 m5
o) Sl)amet'oxazole.
@ith the exception of the requirements for shape. the ta)lets compl3 with the requirements stated
under %a)lets and with the followin& requirements$
:ontent of t&imethop&imB :1-)189-/3 0.01=5 to 0.0215 5.
:ontent of $ulfamethoxazoleB :10)1193/3 S 0.0,25 to 0.10:5 5.
0#entifi"ation Com!l1 3it' t'e tests #escribe# n#er Co-trimoxazole $ablets.
!$$a' Carr1 ot t'e Assa1s )or trimet'o!rim an# )or sl)amet'oxazole #escribe# n#er Co-
trimoxazole $ablets.
+abelling $'e label states t'e -antities o) $rimet'o!rim an# o) Sl)amet'oxazole in eac' tablet.
7. 3i$$olution ,e$ting of Soli# /&al 3o$age >o&m$
%his section pro<ides information on the pharmacopoeial dissolution test and &uidance on its
function and application in indi<idual mono&raphs of the /ritish Pharmacopoeia for ta)lets and
capsules$
1. !ppa&atu$
$'ree t1!es o) a!!arats are no3 #escribe# in t'e ;ritis' an# *ro!ean "'armaco!oeiasA t'e
bas?et( t'e !a##le an# t'e )lo3-t'ro5' cell. $'e #escri!tions are concor#ant 3it' t'ose !blis'e#
in t'e Bnite# States "'armaco!eia 0BS"2. O) t'e t3o establis'e# a!!arats 0bas?et an# !a##le2
t'e !a##le is no3 t'e a!!arats o) c'oice )or man1 !re!arations. Ho3e.er( 3'ere a !blis'e# test
ses t'e bas?et( 3or? to .ali#ate a c'an5e to t'e !a##le met'o# is not contem!late#. $'e )lo3-
t'ro5' cell ma1 be more a!!ro!riate )or !re!arations o) !oorl1 solble acti.e in5re#ients 0see
section 52.
2. ,e$t "on#ition$ an# a""eptan"e "&ite&ia
2.1 ,e$t "on#ition$ "'armaco!oeial tests sin5 eit'er t'e bas?et or t'e !a##le are base# on
t'e !rinci!le o) o!eratin5 n#er Jsin? con#itionsJ( t'at is( in a manner sc' t'at material alrea#1 in
soltion #oes not exert a mo#i)1in5 e))ect on t'e rate o) #issoltion o) t'e remain#er. JSin?
con#itionsJ normall1 occr in a .olme o) #issoltion me#im t'at is at least 5 to10 times t'e
satration .olme. $'e stan#ar#ise# con#itions 'a.e been c'osen to !ro.i#e a 5entle
'1#ro#1namic re5imen. J"'1siolo5icalJ me#ia are !re)erre# to 3ater>or5anic sol.ent mixtres or
soltions incor!oratin5 sr)actants.
2.2 In t'e interests o) international 'armonisation t'e ;ritis' "'armaco!oeia Commission
re.ie3e# t'e testin5 con#itions s!eci)ie# in t'e ;ritis' "'armaco!oeia 1,,3 an# a#o!te# a
#issoltion me#im .olme o) ,00 ml instea# o) 1000 ml as t'e norm an# no3 re-ires t'e anal1st
to test 8 in#i.i#al tablets or ca!sles instea# o) 5. $'e latter c'an5e 3as ma#e b1 means o) an
amen#ment to A!!en#ix FII % incl#e# in t'e A##en#m 1,,5 to t'e ;ritis' "'armaco!oeia 1,,3.
+ollo3in5 consltation o) man)actrers( t'e !blis'e# tests( 3'ere.er a!!ro!riate( 3ere also
amen#e# b1 means o) t'is A##en#m to con)orm to t'e re.ise# stan#ar#ise# con#itions. Ho3e.er(
c'an5es to t'e .olme o) t'e #issoltion me#im 3ere not ma#e in cases sc' as %i5oxin $ablets(
3'ere t'ere 3as an in#ication o) correlation bet3een t'e reslts o) in-<i<o bioa.ailabilit1 an# t'e
establis'e# !'armaco!oeial test an# in ot'er jsti)ie# cases.
2.3 $'e re.ise# stan#ar#ise# ;" con#itions )or !blis'e# tests sin5 eit'er t'e bas?et or t'e
!a##le are7
rotation s!ee#7100 r!m 0bas?et2( 50 r!m 0!a##le2 #issoltion me#im .olme7 ,00 ml
#issoltion me#im com!osition7 a-eos( commonl1 0.16 HCl or !'os!'ate b))ers o) !H 8.=
to :.8
nmber o) nits teste#7 8 0!ls 8( i) retest2.
$'e nmber o) nits teste# is s!eci)ie# in A!!en#ix FII % A ot'er con#itions are s!eci)ie# in t'e
rele.ant in#i.i#al mono5ra!'s.
2./ !""eptan"e "&ite&ia $'e stan#ar#ise# ;" criteria )or !blis'e# tests sin5 eit'er t'e bas?et
or t'e !a##le are t'at( )or eac' nit teste#( not less t'an :0N o) t'e acti.e in5re#ient or in5re#ients
#issol.es 3it'in /5 mintes. I) one nit )ails to meet t'is re-irement( a retest ma1 be carrie# ot
sin5 t'e same nmber o) nitsA all nits in t'e retest mst com!l1. $'ese criteria are s!eci)ie# in
A!!en#ix FII % an# a!!l1 nless ot'er3ise state# in t'e in#i.i#al mono5ra!'. It is inten#e# to
maintain t'ese stan#ar#ise# criteria as t'e norm in !blis'e# mono5ra!'s.
2.5 It s'ol# be note# t'at t'e :0N #issoltion re-irement mst be met b1 each o) t'e tablets
or ca!sles teste# 0or b1 all bt one o) t'e total nmber o) nits i) a retest is !er)orme#2 an# t'at t'e
!ercenta5e is in terms o) t'e !rescribe# or stated amont 0t'at is( t'e labelle# claim2. $a?in5
accont o) !ermissible assa1 ran5es an# content ni)ormit1( t'is !'armaco!oeial 0t'at is( s'el)-li)e2
#issoltion re-irement is consi#ere# to o))er an acce!table #e5ree o) assrance o) Jtotal
#issoltionJ. $'e c'oice o) a time is( o) necessit1( some3'at arbitrar1 bt /5 mintes is consi#ere#
satis)actor1 )or t'e majorit1 o) con.entional-release 0non-mo#i)ie#-release2 !ro#cts.
2.8 Com!liance 3it' t'e stan#ar# ;" re-irement !ro.i#es an assrance t'at most o) t'e acti.e
in5re#ient 3ill be #issol.e# in a reasona)le time 3'en t'e !re!aration is sbjecte# to mil# a5itation
in an a-eos en.ironment. &'ile sc' an assrance #oes not( o) corse( 5arantee bioa.ailabilit1(
it si5ni)icantl1 re#ces t'e li?eli'oo# o) nsatis)actor1 bioa.ailabilit1 #e to ina#e-ate #issoltion.
2.: Stan#ar#ise# con#itions an# limits are consi#ere# a!!ro!riate )or a !'armaco!oeial test t'at
is inten#e# )or a!!lication to mono5ra!'s co.erin5 !ro#cts )rom #i))erent man)actrers. It mi5't
be ar5e# t'at non-stan#ar#ise# con#itions an# limits 3ol# be more #iscriminator1 bt Jtailor-
ma#eJ test con#itions an# limits ma1 intro#ce !ro#ct bias an# ma1 #iscriminate nnecessaril1
bet3een !ro#cts t'at are e-all1 acce!table )rom a clinical .ie3-!oint. Similarl1 3it' s))icient
mani!lation o) t'e test con#itions #issoltion o) almost an1 !ro#ct can be ac'ie.e#. I#eall1 t'e
test s'ol# re)lect clinicall1 si5ni)icant #i))erences in bioa.ailabilit1 arisin5 )rom #i))erences in
#issoltion in sc' a 3a1 t'at clinicall1 acce!table )ormlations 3ill !ass 3'ereas clinicall1
nacce!table )ormlations 3ill )ail.
2.= Anot'er isse t'at 'as been consi#ere# in relation to test con#itions an# criteria is t'at o)
mlti!le-!oint #issoltion !ro)iles as o!!ose# to sin5le-!oint #issoltion tests. It 'as been concl#e#
t'at )or con.entional-release !re!arations sc' an extension o) testin5 is not 5enerall1 necessar1 or
a!!ro!riate )or !'armaco!oeial !r!oses.
3. >un"tion
3.1 $'e ;" !olic1 o) selecti.e a!!lication o) #issoltion testin5 is base# on an assm!tion t'at
sc' testin5 is rele.ant to t'e clinical sitation an# t'at( in &eneral( a con.entional-release
!re!aration o) alrea#1 !ro.en bioa.ailabilit1( 3'ic' consistentl1 com!lies 3it' t'e re-irement( is
nli?el1 to 5i.e rise to major !roblems o) bioa.ailabilit1. &'ile t'e ltimate objecti.e o) #issoltion
testin5 mi5't be #escribe# as ensrin5 a#e-ate an# re!ro#cible bioa.ailabilit1 3it'ot recorse
to rotine in-<i<o testin5( t'is i#eal 5oal is consi#ere# nrealistic in relation to t'e majorit1 o)
!'armaco!oeial a!!lications. It ma1 be ac'ie.e# sometimes b1 a man)actrerJs in-'ose
#issoltion testin5 o) a !articlar !ro#ct )or 3'ic' in <itroEin <i<o correlation 'as been
#emonstrate#.
3.2 $'e !blis'e# stan#ar#s o) t'e ;ritis' "'armaco!oeia are a!!lie# to !ro#cts t'at 'a.e
recei.e# a !ro#ct licence in accor#ance 3it' t'e rele.ant re5lations. Sc' !ro#cts 3ill 'a.e met
an1 necessar1 re-irements )or bioa.ailabilit1 an# bioe-i.alence an# #issoltion testin5 3ill 'a.e
been carrie# ot as !art o) t'e #e.elo!ment st#ies. Once a !ro#ct is license#( a #issoltion test
ma1 be re-ire# rotinel1 as !art o) -alit1 assrance to #emonstrate consistenc1 o) !rocess
be)ore t'e release o) eac' batc' o) t'e )inis'e# !ro#ct or( 3'en necessar1( to !ro.i#e e.i#ence to
s!!ort c'an5es in man)actre sc' as minor c'an5es in )ormlation or !rocess( c'an5es in site
or c'an5es in imme#iate !ac?a5in5 materials.
3.3 Com!liance 3it' a !'armaco!oeial #issoltion test #oes not b1 itsel) 5arantee
bioa.ailabilit1 an# is not necessaril1 an a#e-ate basis )or j#5in5 bioe-i.alence bet3een
!re!arations. Ho3e.er( sc' a !'armaco!oeial test contribtes to an o.erall assrance o) t'e
consistenc1 o) t'e -alit1 o) a !re!aration 3it' res!ect to its #r5 release !ro!erties.
/. !ppli"ation
/.1 In re.ie3in5 t'e )tre a!!lication o) #issoltion testin5 in t'e ;ritis' "'armaco!oeia( t'e
;ritis' "'armaco!oeia Commission #eci#e# t'at #issoltion testin5 3ol# be a!!lie# to a 3i#er
ran5e o) ca!sles an# tablets t'an be)ore. It #i# not( 'o3e.er( a#o!t a !olic1 o) ni.ersal
a!!lication an# a #issoltion re-irement 3ill not be incl#e# atomaticall1 in e.er1 ca!sle an#
tablet mono5ra!'.
/.2 As a &eneral &uideline( it is ex!ecte# t'at all ne3 mono5ra!'s )or con.entional-release
ca!sles an# tablets 3ill contain a #issoltion re-irement exce!t 0i2 3'ere t'e solbilit1 o) t'e
acti.e in5re#ient is 10N or better in 3ater or in #ilte '1#roc'loric aci#( at a!!roximatel1 209A 0ii2
3'ere t'e natre or inten#e# se o) t'e !re!aration ren#ers a #issoltion test ina!!ro!riate 0)or
exam!le( li-i#-containin5 ca!sles( #is!ersible( e))er.escent or solble tablets2 or 0iii2 in ot'er
jsti)ie# circmstances.
/.3 $'e same 5i#eline is bein5 a!!lie# to a re.ie3 o) t'ose ca!sle an# tablet mono5ra!'s t'at
3ere !blis'e# in t'e ;ritis' "'armaco!oeia 1,,3. *ac' case is bein5 j#5e# on its merits an#
#e!artres )rom t'e norm acce!te# 3'ere a!!ro!riate. A !ro.isional list o) !blis'e# mono5ra!'s
)or 3'ic' it is not inten#e# to #e.elo! a !'armaco!oeial #issoltion test is !ro.i#e# at t'e en# o)
t'is text. A##ition o) tests to t'e remainin5 mono5ra!'s is bein5 carrie# ot n#er t'e CommissionJs
re.ision !ro5ramme in accor#ance 3it' #e)ine# !riorities an# a.ailable resorces.
/./ $ests 3ere a##e# to a consi#erable nmber o) mono5ra!'s b1 means o) t'e A##en#m
1,,: to t'e ;ritis' "'armaco!oeia 1,,3 an# more 'a.e been a##e# in t'is ne3 e#ition. It is
em!'asise# t'at( 3'ile t'e objecti.e is to incl#e a Jstan#ar#J !'armaco!oeial test 3'ere.er
a!!ro!riate( t'e circmstances )or eac' !re!aration are consi#ere# in#i.i#all1 in consltation 3it'
t'e man)actrers. It s'ol# be a!!reciate#( 'o3e.er( t'at t'e retros!ecti.e a##ition o) #issoltion
tests is not 3it'ot its #i))iclties. $'e !roblems are most acte )or t'ose 3ell-establis'e#
!re!arations t'at are man)actre# b1 a 3i#e ran5e o) com!anies( eac' 3it' its o3n #issoltion
s!eci)ication. A !ra5matic a!!roac' is bein5 ta?en to #e.elo!in5 com!romise test !roce#res in
t'ese circmstances. It 'as sometimes been !ossible to 'armonise 3it' t'e test con#itions
s!eci)ie# in t'e corres!on#in5 mono5ra!' in t'e BS".
/.5 %e.elo!ment o) a test )or !re!arations containin5 acti.e sbstances o) lo3 a-eos
solbilit1( )or 3'ic' a!!lication o) t'e !a##le met'o# sin5 stan#ar# a-eos me#ia ma1 not be
tec'nicall1 )easible( 'as been #e)erre# !en#in5 t'e otcome o) )rt'er collaborati.e 3or? 0see
section 52.
D. +ow-$olubilit' p&epa&ation$
5.1 Certain ;" mono5ra!'s )or tablets or ca!sles containin5 acti.e sbstances o) lo3 solbilit1
in a-eos me#ia 3ere ori5inall1 i#enti)ie# as re-irin5 a #issoltion s!eci)ication. "ro5ress in
#e.elo!in5 sitable s!eci)ications )or t'ese !re!arations 'as been #i))iclt.
5.2 One 3a1 o) resol.in5 t'e !roblem is se o) me#ia mo#i)ie# b1 t'e a##ition o) an or5anic
sol.ent( sc' as et'anol( or a sr)actant. $'is a!!roac' 'as been a#o!te# b1 t'e BS" an# as an
interim measre in certain ;" mono5ra!'s. %issoltion tests base# on t'ose in t'e BS" sin5
mo#i)ie# me#ia 3ere !blis'e# in t'e A##en#m 1,,2 to t'e ;ritis' "'armaco!oeia 1,== )or
Cortisone $ablets 030N !ro!anol2( Griseo)l.in $ablets 01.5N so#im #o#ec1l sl!'ate2 an#
S!ironolactone $ablets 00.1N so#im #o#ec1l sl!'ate2( )ollo3in5 laborator1 3or? to #emonstrate
a!!licabilit1 to !ro#cts on t'e BD mar?et an# in t'e ?no3le#5e t'at( in t'e absence o) a !blis'e#
;" test( t'at in t'e BS" 3as sall1 cite#.
5.3 &'ile sc' an a!!roac' ma1 be .ali#ate# b1 in <i<o correlation on a !ro#ct-s!eci)ic basis(
#obt 'as contine# to be ex!resse# as to its .ali#it1 )or !'armaco!oeial !r!oses. %e!artre )rom
t'e 5entle '1#ro#1namic re5imen re!resente# b1 t'e a-eos me#ia normall1 se# in ;" tests
calls into -estion t'e rele.ance o) t'e s!eci)ication es!eciall1 as an in#icator o) bioa.ailabilit1 an#
in relation to !ro#ct com!arisons. &it' res!ect to t'e t3o t1!es o) mo#i)ier( some 'a.e ar5e# t'at
t'e se o) sr)actants is more li?el1 to 5i.e !roblems o) !ro#ct bias 3'ile ot'ers 'a.e s55este#
t'at 3ater>or5anic sol.ent mixtres can a#.ersel1 a))ect t'e initial #isinte5ration o) t'e tablet. A
consenss 'as emer5e#( 'o3e.er( t'at in circmstances 3'ere se o) a mo#i)ie# me#im is
na.oi#able( a lo3 concentration o) so#im #o#ec1l sl!'ate is t'e mo#i)ier o) c'oice.
5./ Anot'er a!!roac' to #ealin5 3it' lo3-solbilit1 !re!arations is to se a )lo3-t'ro5' cell
a!!arats. $'is is #escribe# in t'e *ro!ean "'armaco!oeia 0"' *r( 2.,.3 A ;"( A!!en#ix FII % 2
an# it 3as !ro!ose# t'at t'is met'o# s'ol# no3 be in.esti5ate# as a !ossible met'o# o) c'oice )or
lo3-solbilit1 !re!arations since it 3ol# o.ercome t'e objections to t'e se o) Jnon-!'1siolo5icalJ
me#ia. In .ie3 o) t'e lac? o) 3i#e ex!erience o) t'e se o) t'is met'o# in t'e Bnite# Din5#om( it
3as reco5nise# t'at collaborati.e !ractical 3or? 3ol# be necessar1 to stan#ar#ise t'e tec'ni-e
an# ex!lore its !otential )or !'armaco!oeial a!!lications. A 3or?in5 !art1 3as establis'e# n#er t'e
as!ices o) ;" Committee +7 "'armac1 to carr1 ot t'is 3or? 3it' !artici!ation )rom in#str1(
control laboratories an# licensin5 assessors. $'e st#1 3ol# )ocs on !re!arations o) t3o or t'ree
!oorl1 solble acti.e sbstances. In a##ition to in.esti5atin5 t'e se o) t'e )lo3-t'ro5' a!!arats(
t'e st#1 3ol# loo? at t'e se o) so#im #o#ec1l sl!'ate in conjnction 3it' t'e !a##le
a!!arats. ;ase# on t'e !reliminar1 )in#in5s )rom t'e )irst !'ase o) t'e trial( it 'as been
recommen#e# t'at t'is latter a!!roac' s'ol# be a#o!te# )or Cortisone $ablets an# s55este# t'at
it mi5't se)ll1 be ex!lore# )or ot'er )ormlations. +rt'er 3or? 3ill be carrie# ot 3'en resorces
!ermit.
E. ;o#ifie#-&elea$e p&epa&ation$
8.1 An1 consi#eration o) t'e -alit1 o) mo#i)ie#-release !re!arations in relation to t'eir sa)et1 an#
e))icac1 mst incl#e attention to t'e release c'aracteristics o) t'ese !ro#cts. A man)actrer mst
be able to !ro.i#e t'e licensin5 at'orit1 3it' an assrance t'at t'e #issoltion !ro)ile re)lects in
<i<o !er)ormance( 3'ic' in trn is com!atible 3it' t'e recommen#e# #osa5e sc'e#le )or t'e
s!eci)ic !ro#ct.
8.2 $'e 5eneral mono5ra!'s )or Ca!sles an# $ablets incl#e a "ro#ction re-irement t'at a
sitable test is carrie# ot to #emonstrate t'e a!!ro!riate release o) t'e acti.e in5re#ient or
in5re#ients. &it' res!ect to !ro.i#in5 tests in in#i.i#al mono5ra!'s( 'o3e.er( it 'as been
concl#e# relctantl1( )ollo3in5 #etaile# #iscssion an# !ractical in.esti5ation( t'at it is not !ossible
to !ro.i#e satis)actor1 !'armaco!oeial control o) t'e #issoltion !ro)ile o) t'e majorit1 o) mo#i)ie#-
release !re!arations. %ata obtaine# in a st#1 o) t'eo!'1lline )ormlations( )or exam!le( in#icate#
t'at it 3as not !ossible e.en to #e.ise sim!li)ie# #issoltion criteria )or sc' !re!arations to ensre
t'at #ose-#m!in5 #i# not occr an# t'at an acce!table amont o) t'e acti.e in5re#ient 3as
e.entall1 release#. ;et3een-!ro#ct #i))erences are sc' as to !recl#e t'e settin5 o) meanin5)l
!'armaco!oeial limits e.en )or t'ese more limite# objecti.es.
Soli# o&al-#o$age fo&m monog&aph$ fo& whi"h it i$ not inten#e# to #e*elop a #i$$olution te$t
Ca!sles
Amanta#ine Ca!sles
Am!icillin Ca!sles
C'lormet'iazole Ca!sles
Clo)ibrate Ca!sles
Clomi!ramine Ca!sles
Cloxacillin Ca!sles
Co-#ant'rsate Ca!sles
C1anocobalaminH
5:
CoI Ca!sles
%ot'ie!in Ca!sles
%oxe!in Ca!sles
*stramstine "'os!'ate Ca!sles
*t'osximi#e Ca!sles
+lcloxacillin Ca!sles
+lraze!am Ca!sles
Halibt-li.er Oil Ca!sles
H1#rox1rea Ca!sles
@incom1cin Ca!sles
@1mec1cline Ca!sles
6exiletine Ca!sles

$ablets
Alminim H1#roxi#e $ablets
Amitri!t1line

$ablets
Ascorbic Aci# $ablets
As!irin $ablets( %is!ersible
As!irin $ablets( *))er.escent Solble
Atenolol $ablets
Atro!ine $ablets
;enztro!ine $ablets
;etamet'asone So#im "'os!'ate $ablets
;rom!'eniramine $ablets
;sl!'an $ablets
Calcim Glconate $ablets( *))er.escent
Calcim @actate $ablets
Cascara $ablets
C'lor#iaze!oxi#e H1#roc'lori#e $ablets
C'lor!'eniramine $ablets
C'oline $'eo!'1llinate $ablets
Cloni#ine $ablets
Co-co#a!rin $ablets( %is!ersible
Co#eine "'os!'ate $ablets
Colc'icine $ablets
Colistin $ablets
Co-ma5al#rox $ablets
Co-trimoxazole $ablets( %is!ersible
%esi!ramine $ablets
%exam!'etamine $ablets
%extromorami#e $ablets
%ic1clomine $ablets
%i5itoxin $ablets
%i'1#roco#eine $ablets
%ocsate $ablets
%ot'ie!in $ablets
*!'e#rine H1#roc'lori#e $ablets
*tami!'1lline $ablets
1

*t'ambtol $ablets
+erros Glconate $ablets
+erros Sl!'ate $ablets
+l!'enazine $ablets
Gl1cer1l $rinitrate $ablets
Ganet'i#ine $ablets
H1#rotalcite $ablets
H1#rox1c'loro-ine $ablets
H1oscine ;t1lbromi#e $ablets
H1oscine $ablets
Imi!ramine $ablets
@abetalol $ablets
@incom1cin $ablets
1

@it'im Carbonate $ablets
6a5nesim $risilicate $ablets( Com!on#
6ebe.erine $ablets
6ena#iol "'os!'ate $ablets
6e!1ramine $ablets
6et'a#one $ablets
6etoclo!rami#e $ablets
6eto!rolol $ablets
Neom1cin $ablets
Neosti5mine $ablets
Nicotinami#e $ablets
Nicotin1l Alco'ol $ablets
Nitro)rantoin $ablets
Orci!renaline $ablets
Or!'ena#rine H1#roc'lori#e $ablets
Ox!renolol $ablets
"ancreatin $ablets
"enicillamine $ablets
"entaer1t'ritol $etranitrate $ablets
"entobarbitone $ablets
"et'i#ine $ablets
"'enelzine $ablets
"in#olol $ablets
"i!erazine Citrate $ablets
1

"ol#ine $ablets
"otassim C'lori#e $ablets( *))er.escent
"romazine $ablets
"romet'azine H1#roc'lori#e $ablets
"ro!ant'eline $ablets
"ro!ranolol $ablets
"rotri!t1line $ablets
"se#oe!'e#rine $ablets
"1ri#osti5mine $ablets
"1ri#oxine $ablets
4aniti#ine $ablets
Salbtamol $ablets
Senna $ablets
So#im ;icarbonate $ablets( Com!on#
So#im C'lori#e $ablets
So#im Citrate $ablets
Sotalol $ablets
Stilboestrol $ablets
$erbtaline $ablets
$'iamine $ablets
$'iori#azine $ablets
$'1moxamine $ablets
$imolol $ablets
$ranexamic Aci# $ablets
$ri)lo!erazine $ablets
$rime!razine $ablets
$ri!roli#ine $ablets
1. 6ono5ra!' o) t'e ;ritis' "'armaco!oeia 0Eeterinar12