Shojaee Saeed, Kaialy Waseem, Cumming Kenneth Iain, Nokhodchi Ali
a Chemistry and Drug Delivery Group, Medway School of Pharmacy , University of Kent , Kent , UK .
b Faculty of Science and Engineering, School of Pharmacy , University of Wolverhampton , Wolverhampton , UK , and.
Pharm Dev Technol. 2016 Mar;21(2):189-95. doi: 10.3109/10837450.2014.982823. Epub 2014 Nov 20.
Polyethylene oxide (PEO) undergoes structural adjustments caused by elevated temperatures, which results in loss of its stability within direct compression tablets. The aim of this study was to evaluate the influence of filler solubility on the drug delivery process of matrix tablets containing drugs with different water-solubility properties and stored at elevated temperature. The results demonstrated that in the case of propranolol HCl (highly water-soluble) tablet matrices, soluble lactose promoted drug release, whereas, a stable release of drug was observed with insoluble DCP. A drug release pattern similar to the propranolol HCl formulation containing DCP was obtained for hydrophilic matrix tablets containing either lactose or DCP for the less water-soluble drug, zonisamide. In the case of the partially water-soluble drug, theophylline, formulated with lower molecular weight PEO 750, drug release increased considerably in the presence of both fillers with increasing storage time, however a stable release rate (similar to fresh samples) was observed in the case of higher molecular weight PEO 303 tablet matrices containing theophylline with either lactose or DCP. The hydration properties (e.g. solubility) of the diluents had a considerable effect on drug release behavior from various model matrices; this effect was dependent on both molecular weight of PEO and solubility of drug.
聚环氧乙烷(PEO)会因温度升高而发生结构调整,这会导致其在直接压片中失去稳定性。本研究的目的是评估填充剂溶解度对含有不同水溶性药物且在高温下储存的基质片剂药物释放过程的影响。结果表明,对于盐酸普萘洛尔(高度水溶性)片剂基质,可溶性乳糖促进药物释放,而使用不溶性磷酸氢钙(DCP)时观察到药物的稳定释放。对于含有乳糖或DCP的亲水性基质片剂,对于水溶性较低的药物唑尼沙胺,获得了与含有DCP的盐酸普萘洛尔制剂相似的药物释放模式。对于用低分子量PEO 750配制的部分水溶性药物茶碱,在两种填充剂存在下,药物释放随着储存时间的增加而显著增加,然而,在含有茶碱以及乳糖或DCP的高分子量PEO 303片剂基质中观察到稳定的释放速率(类似于新鲜样品)。稀释剂的水化性质(如溶解度)对各种模型基质的药物释放行为有相当大的影响;这种影响取决于PEO的分子量和药物的溶解度。