Application of a ternary HP-尾-CD-complex approach to improve the dissolution performance of a poorly soluble weak acid under biorelevant conditions

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• 作者：Thomas Zoeller^a ; ¹ ; Jennifer B. Dressman^a ; Sandra Klein^b ; ^{Sandra.Klein@uni-greifswald.de}
• 关键词：Glyburide ; Poor solubility ; Solid dispersions ; HP-尾-CD ; BCS ; Binary complexes ; Ternary complexes ; Dissolution ; Bioavailability
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：1 July, 2012
• 卷：430
• 期：1-2
• 页码：176-183
• 文件大小：690 K

摘要

Over the last decades the poor solubility of new drugs has become an important issue, with one of the main challenges being to develop oral dosage forms with acceptable bioavailability for such compounds. The specific purpose of our study was to combine the advantages of cyclodextrins with those of solid dispersion approaches to improve the bioavailability of poorly soluble weak acids. Glyburide, an antidiabetic, was used as a model drug. First, binary drug inclusion complexes were prepared with 2-hydroxypropyl-尾-cyclodextrin. Next, solid glyburide dispersions were prepared with polyvinylpyrrolidone (PVP) and a relatively new hydrophilic copolymer, Kollicoat^庐 IR. Finally, to check for potential synergistic effects of the two types of excipients, ternary inclusion complexes were formulated by keeping the 1:2 drug:CD ratio constant but varying the polymer concentration (5-20%). The formulations were analyzed by differential scanning calorimetry and subjected to solubility and dissolution experiments in compendial and biorelevant media. The results of the study clearly indicate that all formulations result in better in vitro performance of the drug. Best results were obtained with the ternary inclusion complexes containing 10%Kollicoat^庐 IR or 20%PVP K30. This formulation approach, particularly with the new polymer, appears to be promising in terms of enhancing the bioavailability of BCS class II drugs.