Laboratory of Food, Drug and Cosmetics (LTMAC), School of Health Sciences, University of Brasília, 70910-900 Brasília, Federal District, Brazil.
Faculty of Ceilândia, University of Brasília (UnB), 72220-900 Ceilândia, Federal District, Brazil.
J Pharm Sci. 2018 Jan;107(1):286-296. doi: 10.1016/j.xphs.2017.08.014. Epub 2017 Aug 26.
This work aimed at obtaining an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone (poly(1-vinylpyrrolidone-co-vinyl acetate) [PVP/VA]), Klucel ELF (2-hydroxypropyl ether cellulose [HPC]), and Soluplus (SOL, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an e-tongue. All materials became homogeneous and dense after HME processing. Thermal and structural analyses demonstrated drug amorphization, whereas IR spectroscopy evidenced drug stability and drug-excipient interactions in HME systems. Extrudates presented a significant increase in dissolution rate compared to ITZ raw material, mainly with formulations containing PVP/VA and HPC. A pronounced improvement in taste masking was also identified for HME systems, especially in those containing higher amounts of SOL and HPC. Data showed polymers act synergistically favoring formulation functional properties. Predicted best formulation should contain ITZ 25.0%, SOL 33.2%, HPC 28.9%, and PVP/VA 12.9% (w/w). Optimized response considering dissolution rate and palatability reinforces the benefit of polymer combinations.
本工作旨在通过热熔挤出（HME）结合使用不同的聚合物来获得具有良好口感和溶解速率的优化伊曲康唑（ITZ）固体口服制剂，根据单纯形质心混合设计。为此，使用没有循环的实验室 HME 设备在恒温下加工聚合物 Plasdone（聚（1-乙烯基吡咯烷酮-co-醋酸乙烯酯）[PVP/VA]）、Klucel ELF（2-羟丙基醚纤维素[HPC]）和 Soluplus（SOL，聚己内酯-聚醋酸乙烯酯-聚乙二醇）。通过物理化学分析、电子舌评估溶解速率和口感对样品进行了表征。HME 处理后所有材料均变得均匀且致密。热分析和结构分析表明药物无定形化，而红外光谱表明药物在 HME 系统中稳定且存在药物-赋形剂相互作用。与 ITZ 原料药相比，挤出物的溶解速率显著提高，主要是含有 PVP/VA 和 HPC 的制剂。还发现 HME 系统的掩味效果明显改善，特别是含有较高含量 SOL 和 HPC 的系统。数据表明聚合物具有协同作用，有利于制剂功能特性。预测的最佳配方应含有 ITZ 25.0%、SOL 33.2%、HPC 28.9%和 PVP/VA 12.9%（w/w）。考虑溶解速率和口感的优化响应增强了聚合物组合的益处。
