Department of Pharmaceutics, University of Kuopio, FI-70211 Kuopio, Finland.
J Pharm Sci. 2009 Oct;98(10):3676-90. doi: 10.1002/jps.21689.
The aim of this study was to determine, whether interactions between a drug and hydrophobic polymer matrix are present, and if so, how they affect the drug release. In addition, the most important formulation parameters, for example porosity or structure of the tablet, which have the greatest impact on drug release, were defined. Six different drug compounds, that is allopurinol, acyclovir, metronidazole, paracetamol, salicylamide and theophylline, were used in different formulations with hydrophobic starch acetate (DS 2.7) as a matrix forming polymer. Results indicate that the formulation parameters describing directly or indirectly the structure of the matrix, such as porosity, compaction force and the particle size fraction of the filler-binder, have the strongest impact on drug release. The contribution of drug property based variables is not as high as formulation parameters, but they cannot be overlooked. The contribution of water solubility and dissolution rate of the compound are obvious, but there are other significant parameters, which describe the hydrophobic and hydrophilic regions of the molecule, that also affect the drug release. This can be seen especially with the salicylamide: compound which appears to have a strong and sufficiently high hydrophobic region that interacts with starch acetate and impairs the drug release.
本研究旨在确定药物与疏水性聚合物基质之间是否存在相互作用，如果存在，它们如何影响药物释放。此外，还确定了对药物释放影响最大的最重要的制剂参数，例如片剂的孔隙率或结构。使用疏水性醋酸淀粉（DS 2.7）作为基质形成聚合物，将六种不同的药物化合物，即别嘌醇、阿昔洛韦、甲硝唑、扑热息痛、水杨酰胺和茶碱，用于不同的制剂中。结果表明，直接或间接描述基质结构的制剂参数，如孔隙率、压缩力和填充剂-粘合剂的粒径分数，对药物释放的影响最大。基于药物性质的变量的贡献不如制剂参数高，但也不能忽视。化合物的水溶性和溶解速率的贡献是明显的，但还有其他重要的参数，描述分子的疏水区和亲水区，也会影响药物释放。这在水杨酰胺化合物中尤其明显：该化合物似乎具有很强且足够高的疏水区，与醋酸淀粉相互作用，从而阻碍药物释放。
