Programa de Pos-Graduacao em Saude e Meio Ambiente, Universidade da Regiao de Joinville, Joinville, Brazil.
Departamento de Farmacia, Universidade da Regiao de Joinville, Joinville, Brazil.
Curr Drug Deliv. 2021;18(4):460-470. doi: 10.2174/1567201817666201023121948.
Solid Dispersions (SDs) have been extensively used to increase the dissolution of poorly water-soluble drugs. However, there are few studies exploring SDs properties that must be considered during tablet development, like tabletability. Poorly water-soluble drugs with poor compression properties and high therapeutic doses, like gemfibrozil, are an additional challenge in the production of SDs-based tablets.
This study evaluates the applicability of SDs to improve both tabletability and dissolution rate of gemfibrozil. A SD-based tablet formulation was also proposed.
SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as a carrier, according to a 2 factorial design. The formulation variables were gemfibrozil:HPMC ratio, milling speed, and milling time. The response in the factorial analysis was the tensile strength of the compacted SDs. Dissolution rate and solid-state characterization of SDs were also performed.
SDs showed simultaneous drug dissolution enhancement and improved tabletability when compared to corresponding physical mixtures and gemfibrozil. The main variable influencing drug dissolution and tabletability was the gemfibrozil:HPMC ratio. Tablets containing gemfibrozil- HPMC-SD (1:0.250 w/w) and croscarmellose sodium showed fast and complete drug release, while those containing the same SD and sodium starch glycolate exhibited poor drug release due to their prolonged disintegration time.
SDs proved to be effective for simultaneously improving tabletability and dissolution profile of gemfibrozil. Tablets containing gemfibrozil-HPMC-SD and croscarmellose sodium as disintegrating agent showed improved drug release and good mechanical strength, demonstrating the potential of HPMC-based SDs to simultaneously overcome the poor dissolution and tabletability properties of this drug.
固体分散体（SDs）已广泛用于提高水溶性差的药物的溶解率。然而，很少有研究探讨在片剂开发过程中必须考虑的 SD 特性，例如可压性。像吉非贝齐这样水溶性差、压缩性能差、治疗剂量高的难溶性药物，在生产基于 SD 的片剂时是一个额外的挑战。
本研究评估 SD 对改善吉非贝齐的可压性和溶解速率的适用性。还提出了一种基于 SD 的片剂配方。
通过球磨法制备 SD，使用羟丙基甲基纤维素（HPMC）作为载体，根据 2 因素设计。制剂变量为吉非贝齐：HPMC 比、研磨速度和研磨时间。该因子分析中的响应是压实 SD 的拉伸强度。还对 SD 的溶解速率和固态特性进行了研究。
与相应的物理混合物和吉非贝齐相比，SD 显示出药物溶解增强和可压性改善的双重效果。影响药物溶解和可压性的主要变量是吉非贝齐：HPMC 比。含有吉非贝齐-HPMC-SD（1:0.250 w/w）和交联羧甲基纤维素钠的片剂表现出快速和完全的药物释放，而含有相同 SD 和交联聚维酮的片剂由于崩解时间延长而表现出较差的药物释放。
SD 被证明可有效同时改善吉非贝齐的可压性和溶解特性。含有吉非贝齐-HPMC-SD 和交联羧甲基纤维素钠作为崩解剂的片剂表现出改善的药物释放和良好的机械强度，表明基于 HPMC 的 SD 具有同时克服该药物较差的溶解和可压性特性的潜力。
