Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion
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- 作者：Suhas G. Gumaste ; Simerdeep Singh Gupta ; Abu T. M. Serajuddin
- 关键词：KEY WORDSfilm casting ; HPMCAS ; itraconazole ; poloxamer 188 ; polymer ; drug ; surfactant miscibility ; polymer ; surfactant miscibility ; solid dispersion ; Soluplus®
- 刊名：The AAPS Journal
- 出版年：2016
- 出版时间：September 2016
- 年：2016
- 卷：18
- 期：5
- 页码：1131-1143
- 全文大小：3,028 KB
- 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Biotechnology; Pharmacy;
- 出版者：Springer US
- ISSN：1550-7416
- 卷排序：18
文摘
In a solid dispersion (SD), the drug is generally dispersed either molecularly or in the amorphous state in polymeric carriers, and the addition of a surfactant is often important to ensure drug release from such a system. The objective of this investigation was to screen systematically polymer-surfactant and polymer-drug-surfactant miscibility by using the film casting method. Miscibility of the crystalline solid surfactant, poloxamer 188, with two commonly used amorphous polymeric carriers, Soluplus® and HPMCAS, was first studied. Then, polymer-drug-surfactant miscibility was determined using itraconazole as the model drug, and ternary phase diagrams were constructed. The casted films were examined by DSC, PXRD and polarized light microscopy for any crystallization or phase separation of surfactant, drug or both in freshly prepared films and after exposure to 40°C/75% RH for 7, 14, and 30 days. The miscibility of poloxamer 188 with Soluplus® was <10% w/w, while its miscibility with HPMCAS was at least 30% w/w. Although itraconazole by itself was miscible with Soluplus® up to 40% w/w, the presence of poloxamer drastically reduced its miscibility to <10%. In contrast, poloxamer 188 had minimal impact on HPMCAS-itraconazole miscibility. For example, the phase diagram showed amorphous miscibility of HPMCAS, itraconazole, and poloxamer 188 at 54, 23, and 23% w/w, respectively, even after exposure to 40°C/75% RH for 1 month. Thus, a relatively simple and practical method of screening miscibility of different components and ultimately physical stability of SD is provided. The results also identify the HPMCAS-poloxamer 188 mixture as an optimal surface-active carrier system for SD.