Materials Research Institute, Athlone Institute of Technology, Westmeath, Ireland.
Synthesis and Solid State Pharmaceutical Centre (SSPC), Bernal Institute, University of Limerick, Limerick, Ireland.
J Pharm Sci. 2018 May;107(5):1372-1382. doi: 10.1016/j.xphs.2018.01.016. Epub 2018 Feb 1.
The optimal design of amorphous solid dispersion formulations requires the use of excipients to maintain supersaturation and improve physical stability to ensure shelf-life stability and better absorption during intestinal transit, respectively. Blends of excipients (surfactants and polymers) are often used within pharmaceutical products to improve the oral delivery of Biopharmaceutical Classification System class II drugs. Therefore, in this study, a dissolution enhancer, poloxamer 407 (P407), was investigated to determine its effect on the dissolution properties and on the amorphous nature of the active pharmaceutical ingredient contained in the formulation. Phase solubility studies of indomethacin (INM) in aqueous solutions of P407 and poly(vinylpyrrolidone-vinyl acetate copolymer) showed an increase in the kinetic solubility of INM compared with the pure drug at 37°C with a K value of 0.041 μg/mL. The solid dispersions showed a higher dissolution rate when compared to pure and amorphous drugs when performed in pH buffer 1.2 with a kinetic solubility of 21 μg/mL. The stability data showed that the amorphous drug in solid solutions with poly(vinylpyrrolidone-vinyl acetate copolymer) and P407 remained amorphous, and the %P407 loading had no effect on the amorphous stability of INM. This study concluded that the amorphous solid dispersion contributed to the increased solubility of INM.
无定形固体分散体配方的最佳设计需要使用赋形剂来维持过饱和度并提高物理稳定性，分别确保货架期稳定性和在肠道转运过程中更好的吸收。赋形剂（表面活性剂和聚合物）的混合物通常用于药物产品中，以改善生物制药分类系统 II 类药物的口服递送。因此，在这项研究中，研究了溶解增强剂泊洛沙姆 407（P407），以确定其对制剂中活性药物成分的溶解性质和无定形性质的影响。吲哚美辛（INM）在 P407 和聚（乙烯基吡咯烷酮-醋酸乙烯酯共聚物）水溶液中的相溶解度研究表明，与纯药物相比，在 37°C 时 INM 的动力学溶解度增加，K 值为 0.041μg/mL。与纯药物和无定形药物相比，在 pH 缓冲液 1.2 中进行时，固体分散体显示出更高的溶解速率，动力学溶解度为 21μg/mL。稳定性数据表明，与聚（乙烯基吡咯烷酮-醋酸乙烯酯共聚物）和 P407 的固体溶液中的无定形药物保持无定形，并且 P407 的负载百分比对 INM 的无定形稳定性没有影响。这项研究得出结论，无定形固体分散体有助于增加 INM 的溶解度。
