Coformer selection based on degradation pathway of drugs: A case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals

被引：65

作者：

Gao, Yuan ^{[2
]}

Gao, Jing ^{[2
]}

Liu, Ziling ^{[1
]}

Kan, Hongliang ^{[1
]}

Zu, Hui ^{[1
]}

Sun, Wanjin ^{[2
]}

Zhang, Jianjun ^{[1
]}

Qian, Shuai ^{[3
]}

机构：

[1] China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Sch Tradit Chinese Med, Nanjing 210009, Jiangsu, Peoples R China

[3] Chinese Univ Hong Kong, Sch Pharm, Shatin, Hong Kong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2012年 / 438卷 / 1-2期

关键词：

Adefovir dipivoxil; Cocrystal; Saccharin; Nicotinamide; Degradation pathway; PHARMACEUTICAL CO-CRYSTALS; PHYSICOCHEMICAL PROPERTIES; ORAL BIOAVAILABILITY; MOLECULAR-COMPLEXES; MELTING-POINTS; SOLUBILITY; STABILITY; PHARMACOKINETICS; CARBAMAZEPINE; ENHANCEMENT;

D O I：

10.1016/j.ijpharm.2012.09.027

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Adefovir dipivoxil (AD) is a bis(pivaloyloxymethyl) prodrug of adefovir with chemical stability problem. It undergoes two degradation pathways including hydrolysis and dimerization during storage. Pharmaceutical cocrystallization exhibits a promising approach to enhance aqueous solubility as well as physicochemical stability. In this study we attempted to prepare and investigate the physiochemical properties of AD cocrystals, which were formed with two coformers having different acidity and alkalinity (weakly acidic saccharin (SAC) and weakly basic nicotinamide (NCT)). The presence of different coformer molecules along with AD resulted in altered physicochemical properties. AD-SAC cocrystal showed great improvement in solubility and chemical stability, while AD-NCT did not. Several potential factors giving rise to different solid-state properties were summarized. Different coformers resulted in different cocrystal formation, packing style and hydrogen bond formation. This study could provide the coformer selection strategy based on degradation pathways for some unstable drugs in pharmaceutical cocrystal design. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：327 / 335

页数：9

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