Compound ;

Amoxicilin tablet

Formulation :

Each tablet contains 500 mg or 875 mg amoxicillin as the trihydrate. Each film-coated, capsule-
shaped, pink tablet is debossed with AMOXIL centered over 500 or 875, respectively. The 875-
mg tablet is scored on the reverse side.

Inactive ingredients: Colloidal silicon dioxide, crospovidone, FD&C Red No. 30 aluminum
lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol,
sodium starch glycolate, and titanium dioxide.

Synthesis amoxicillin :

The immobilized Penicillin G acylase (PGA, EC 3.5.1.11) from Escherichia coli imported
material (Germany): Enzyme immobilization: Glyoxyl-agarose gel was prepared as reported by
Guisan [21]. Penicillin acylase was immobilized in glyoxyl-agarose gel beads, based on the
procedure described by Alvaro et al. [22], but using phenylacetic acid (PAA) instead of
penicillinG sulfoxide as the protecting agent during immobilisation; time of immobilization was
extended to 20 h, determined as the optimum for biocatalyst stability [23]. The glyoxyl-agarose
immobilized penicillin acylase was stored as a wet gel at 5 C. No enzyme inactivation or
leakage has been detected during prolonged storage. Hydroxyphenylglycine methyl ester
(HPGM), 6-aminopeicillanic acid (6-APA) and Amoxicillin trihidrate were obtained from the
Zakariaye Razi Pharmaceutical Company (Iran). All other chemicals were of laboratory grade
prepared from different commercial suppliers. All materials were of pure analytical grade.

Magnesium Stearate (stearic acid): Used as an active ingredient in medicine tablets.

Haram when derived from animal source.

asilylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,

b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in

the presence of a weak base and its hydrochloride,

c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and

d. recovering the amoxicillin trihydrate

the improvement which comprises mixing the products of the acylation reaction of step (b) with water at a highly
acidic pH below 2 to form and precipitate solid amoxicillin hydrochloride and then collecting said solid amoxicillin
hydrochloride and converting it to amoxicillin trihydrate.

2. In a process of claim 1 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by mixing it
with a solution of a liquid, basic high molecular weight aliphatic amine in a water-immiscible organic solvent in the
presence of a substantial amount of water, allowing this mixture to stand for a time sufficient for the completion of the
crystallization of amoxicillin trihydrate and finally collecting said amoxicillin trihydrate.
3. In the process of claim 1 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by adding
it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in a water-immiscible organic solvent
in the presence of a substantial amount of water at about 25 C., allowing this mixture to stand for a time sufficient for
the completion of the crystallization of amoxicillin trihydrate and finally collecting said amoxicillin trihydrate.

4. In the process of claim 1 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by adding
it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in methylene chloride or methyl
isobutyl ketone in the presence of a substantial amount of water, allowing this mixture to stand for a time sufficient for
the completion of the crystallization of amoxicillin trihydrate and finally collecting said amoxicillin trihydrate.

5. In the process of claim 1 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by adding
it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in methylene chloride or methyl
isobutyl ketone in the presence of an amount of water equal to about 10 percent of the weight of said organic solvent
at about 25 C., allowing this mixture to stand for a time sufficient for the completion of the crystallization of
amoxicillin trihydrate and finally collecting said amoxicillin trihydrate.

6. In the process of claim 1 for the production of amoxicillin trihydrate which comprises the consecutive steps of
a. silylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,

b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in

the presence of a weak base and its hydrochloride,

c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and

d. recovering the amoxicillin trihydrate

the improvement which comprises mixing the products of the acylation reaction of step (b) with water at a highly
acidic pH below 2 in the presence of large amounts of chloride ion to form and precipitate solid amoxicillin
hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin trihydrate.

7. In the process of claim 1 for the production of amoxicillin trihydrate which comprises the consecutive steps of
a. silylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,

b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in

the presence of a weak base and its hydrochloride,

c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin thihydrate and

d. recovering the amoxicillin trihydrate

the improvement which comprises mixing the products of the acylation reaction of step (b) with water at a pH below 2
and in the presence of NaCl in an amount by weight of up to 30 percent of the weight of the water used for hydrolysis
to form and precipitate solid amoxicilin hydrochloride and then collecting said solid amoxicillin hydrochloride and
converting it to amoxicillin trihydrate.

8. In the process of claim 1 for the production of amoxicillin trihydrate which comprises the consecutive steps of
a. silylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,

b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in

the presence of a weak base and its hydrochloride,

c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and

d. recovering the amoxicillin trihydrate

the improvement which comprises mixing the products of the acylation reaction of step (b) with a volume of water
which is about one-half the volume of the acylation reaction mixture at a pH below 2 and in the presence of NaCl in
an amount by weight of up to 25 percent of the weight of the water used for hydrolysis to form and precipitate solid
amoxicillin hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin
trihydrate.

9. In the process for the production of amoxicillin trihydrate which comprises the consecutive steps of
a. silylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,

b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in

the presence of a weak base and its hydrochloride,
c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and

d. recovering the amoxicillin trihydrate

the improvement which comprises mixing the products of the acylation reaction of step b) with a volume of water
which is about one-half the volume of the acylation reaction mixture at a pH below 2 and then adding NaCl in an
amount by weight of about 20 percent of the weight of the water used for hydrolysis to form and precipitate solid
amoxicillin hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin
trihydrate.

10. In the process of claim 9 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by
mixing it with a solution of a liquid, basic high molecular weight aliphatic amine in a water-immiscible organic solvent
in the presence of a substantial amount of water, allowing this mixture to stand for a time sufficient for the completion
of the crystallization of amoxicillin trihydrate and finally collecting said amoxicillin trihydrate.

11. In the process of claim 9 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by
adding it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in a water-immiscible organic
solvent in the presence of a substantial amount of water at about 25 C., allowing this mixture to stand for a time
sufficient for the completion of the crystallization of amoxicillin trihydrate and finally collecting said amoxicillin
trihydrate.

12. In the process of claim 9 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by
adding it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in methylene chloride or
methyl isobutyl ketone in the presence of a substantial amount of water, allowing this mixture to stand for a time
sufficient for the completion of the crystallization of amoxicillin trihydrate and finally collecting said amoxicillin
trihydrate.

13. In the process of claim 9 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by
adding it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in methylene chloride or
methyl isobutyl ketone in the presence of an amount of water equal to about 10 percent of the weight of said organic
solvent at about 25 C., allowing this mixture to stand for a time sufficient for the completion of the crystallization of
amoxicillin trihydrate and finally collecting said amoxicillin trihydrate.

14. In the process for the production of amoxicillin trihydrate which comprises the consecutive steps of
a. silylating 6-aminopenicillanic acid with chlorotrimethylsilane or hexamethyldisilazane in methylene chloride in the
presence of triethylamine,

b. by acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in

the presence of dimethylaniline and its hydrochloride,

c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and

d. recovering the amoxicillin trihydrate

the improvement of which comprises mixing the products of the acylation reaction of step b) with a volume of water
which is about one-half the volume of the acylation reaction mixture at a pH below 2 and then adding NaCl in an
amount by weight of about 20 percent of the weight of the water used for hydrolysis to form and precipitate solid
amoxicillin hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin
trihydrate.

15. In the process of claim 14 the process of converting solid amoxicillin hydrochloride to amoxicillin trihydrate by
adding it gradually to a solution of a liquid, basic high molecular weight aliphatic amine in methylene chloride or
methyl isobutyl ketone in the presence of an amount of water equal to about 10 percent of the weight of said organic
solvent at about 25 C., allowing this mixture to stand for a