期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 438, 期 1-2, 页码 327-335出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2012.09.027
关键词
Adefovir dipivoxil; Cocrystal; Saccharin; Nicotinamide; Degradation pathway
资金
- Important National Science & Technology Specific Projects [2011ZX09201-101-02]
- National Natural Science Fund [81202988]
- Peak of Six Major Talents in Jiangsu Province
- Fundamental Research Funds for the Central Universities [JKP2011006]
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.
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