Graduate seminar 1/2013 November 15, 2013

Title

The application of polymer in stabilization of drug solubility in solid dispersions Miss Woralak Leelasornchai Master of Sciences in Pharmaceutical chemistry and natural products /2nd year Asst. Prof. Dr. Soravoot Rujivipat Asst. Prof. Dr. Waree Tiyaboonchai Asst. Prof. Dr. A-nan Ounarun Dr. Nutsawadee Apichartwattana ABSTRACT Low aqueous solubility is a common characteristic in todays biopharmaceutics which

Speaker

Advisor Co-advisor

is a critical determinant of oral bioavailability [1]. There are many techniques which are used to enhance the aqueous solubility like physical, chemical and others techniques. Solid dispersion technology has been used for improving the dissolution rate and bioavailability of poorly water soluble drugs [24]. Solid dispersions are typically prepared by incorporation of the poorly soluble drug into a water-soluble carrier via melt-extrusion or coprecipitation technique [5, 6], resulting in Such processes result in amorphous drug dispersions [7]. Although the amorphous drug dissolves faster compared to its crystalline alternatives, it is not physically stable and may undergo unpredictable crystallization during the shelf-life [810]. The stabilization of amorphous drug solubility by the incorporation of polymer as inhibitory effect has been introduced. The roles of polymer in stabilization mechanism could be: to increasing glass transition temperature of miscible mixture (anti-platicization by the polymer); specific drug-polymer interaction (e.g., hydrogen bonding, ion-dipole) [1113] and an increase in the activation energy for nucleation or alteration of chemical potential of a drug [14-15]. These results in a decrease in local molecular mobility at regular storage temperatures, then the recrystallization would be decreased.

Keywords; solid dispersion, stabilization mechanism, anti-plasticization, drug-polymer interaction, recrystallization

Graduate seminar 1/2013 November 15, 2013

References
1. Dahan A, Hoffman A. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs. J Control Release. 2008 ; 129(1):1-10. 2. Sekiguchi K, Obi N. Studies on absorption of eutectic mixture. I. A comparison of the behavior of eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man. Chem Pharm Bull. 1961; 9:86672. 3. Dannenfelser RM, He H, Joshi Y, Bateman S, Serajuddin AT. Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci. 2004; 93(5):1165-75. 4. Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002; 231(2):131-44. 5. Verreck G, Vandecruys R, De Conde V, Baert L, Peeters J, Brewster ME. The use of three different solid dispersion formulations--melt extrusion, film-coated beads, and a glass thermoplastic system--to improve the bioavailability of a novel microsomal triglyceride transfer protein inhibitor. J Pharm Sci. 2004; 93(5):1217-28. 6. Sethia S, Squillante E. Physicochemical characterization of solid dispersions of carbamazepine formulated by supercritical carbon dioxide and conventional solvent evaporation method. J Pharm Sci. 2002; 91(9):1948-57. 7. Forster A, Hempenstall J, Rades T. Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers. J Pharm Pharmacol. 2001 Mar; 53(3):303-15 8. Kimura K, Hirayama F, Arima H, Uekama K. Effects of aging on crystallization, dissolution and absorption characteristics of amorphous tolbutamide-2-hydroxypropyl-beta-cyclodextrin complex. Chem Pharm Bull (Tokyo). 2000; 48(5):646-50. 9. Chiou WL. Pharmaceutical applications of solid dispersion systems: X-ray diffraction and aqueous solubility studies on griseofulvin-polyethylene glycol 6000 systems. J Pharm Sci. 1977; 66(7):989-91. 10. Suzuki H, Sunada H. Some Factors Influencing the Dissolution of Solid Dispersions with Nicotinamide and Hydroxypropylmethylcellulose as Combined Carriers. Chemical & Pharmaceutical Bulletin. 1998; 46(6):1015-20. 11. Khougaz K, Clas SD. Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers. J Pharm Sci. 2000; 89(10):1325-34. 12. Taylor LS, Zografi G. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm Res. 1997; 14(12):1691-8. 13. Matsumoto T, Zografi G. Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm Res. 1999; 16(11):1722-8. 14. Marsac PJ, Konno H, Taylor LS. A comparison of the physical stability of amorphous felodipine and nifedipine systems. Pharm Res. 2006; 23(10):2306-16. 15. Marsac PJ, Shamblin SL, Taylor LS. Theoretical and practical approaches for prediction of drugpolymer miscibility and solubility. Pharm Res. 2006; 23(10):2417-26.