Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly absorbed drugs

作者：Kawakami Kohsaku^*

来源：Advanced Drug Delivery Reviews, 2012, 64(6): 480-495.

DOI：10.1016/j.addr.2011.10.009

• Poorly soluble drug
• Dissolution
• Bioavailability
• Supersaturation
• Crystal form
• Self-emulsifying formulation
• Solid dispersion
• Amorphous
• Nanosuspension

New chemical entities are required to possess physicochemical characteristics that result in acceptable oral absorption. However, many promising candidates need physicochemical modification or application of special formulation technology. This review discusses strategies for overcoming physicochemical problems during the development at the preformulation and formulation stages with emphasis on overcoming the most typical problem, low solubility. Solubility of active pharmaceutical ingredients can be improved by employing metastable states, salt forms, or cocrystals. Since the usefulness of salt forms is well recognized, it is the normal strategy to select the most suitable salt form through extensive screening in the current developmental study. Promising formulation technologies used to overcome the low solubility problem include liquid-filled capsules, self-emulsifying formulations, solid dispersions, and nanosuspensions. Current knowledge for each formulation is discussed from both theoretical and practical viewpoints, and their advantages and disadvantages are presented.

• 出版日期2012-5-1