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一种用于考察 PEG 和 PEO 对基质片剂影响的药物稳健性设计方法。

A pharma-robust design method to investigate the effect of PEG and PEO on matrix tablets.

机构信息

GL PharmTech Corp., Seongnam, Gyeonggi, 462-807, South Korea.

出版信息

Int J Pharm. 2010 Jun 30;393(1-2):79-87. doi: 10.1016/j.ijpharm.2010.04.009. Epub 2010 Apr 23.

Abstract

Even though polyethyleneoxide (PEO)-polyethyleneglycol (PEG) blends have been used widely for sustained release matrix tablets, evaluations of the effects of PEG or PEO on the matrix properties have been limited. In order to evaluate gelling behavior and drug release profiles of PEG, various contents of the polymers were investigated through a robust experimental design method. When exposed to an aqueous environment, the PEO-PEG matrix hydrated slowly and swelled, causing a thick gel layer to form on the surface, the thickness of which increased significantly depending on the PEG contents. Since polyacrylate plates were used for the study, the matrix was not completely hydrated and gelled even after 5h. However, the results could be applied to the time-oriented responses RD (robust design) models to obtain optimal settings and responses for the observed times. The optimal settings of PEO and PEG were 94.26 and 140.04 mg, respectively (PEG rate of 148.57%). Moreover, as the amount of PEG increased, the release rate also increased. When the formulation contained more than 150% of PEG, most of the drug loaded in the tablet was released in about 12 h. When the amount of PEG was less than 100%, the drug release rate was sustained significantly. Based on the RD optimization model for drug release, the optimal settings were PEG and PEO of 124.3 and 110 mg, respectively (PEG rate of 88.50%). Therefore, PEG rate of about 90-150% is suggested for matrix tablet formulations, and the exact ratio could be formulated according to the resulting tablet's properties.

摘要

尽管聚环氧乙烷(PEO)-聚乙二醇(PEG)共混物已广泛用于缓释基质片剂,但对 PEG 或 PEO 对基质性质的影响的评估有限。为了评估 PEG 的胶凝行为和药物释放曲线,通过稳健实验设计方法研究了聚合物的各种含量。当暴露于水环境时,PEO-PEG 基质缓慢水合并溶胀,导致在表面形成厚凝胶层,其厚度显著取决于 PEG 的含量。由于研究中使用了聚丙烯酸酯板,因此即使在 5 小时后,基质也未完全水合和胶凝。然而,结果可以应用于面向时间的响应 RD(稳健设计)模型,以获得观察时间的最佳设置和响应。PEO 和 PEG 的最佳设置分别为 94.26 和 140.04 毫克(PEG 率为 148.57%)。此外,随着 PEG 用量的增加,释放速率也增加。当制剂中含有超过 150%的 PEG 时,约 12 小时内释放了大部分载入片剂的药物。当 PEG 用量小于 100%时,药物释放速率显著持续。基于药物释放的 RD 优化模型,最佳设置分别为 PEG 和 PEO 为 124.3 和 110 毫克(PEG 率为 88.50%)。因此,建议用于基质片剂制剂的 PEG 率约为 90-150%,具体比例可根据所得片剂的性质进行制定。

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