Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa.
AAPS PharmSciTech. 2013 Dec;14(4):1349-59. doi: 10.1208/s12249-013-0021-7. Epub 2013 Aug 30.
Drug release from hydrophilic matrices is regulated mainly by polymeric erosion, disentanglement, dissolution, swelling front movement, drug dissolution and diffusion through the polymeric matrix. These processes depend upon the interaction between the dissolution media, polymeric matrix and drug molecules, which can be significantly influenced by formulation variables and excipients. This study utilized mathematical parameters to evaluate the impacts of selected formulation variables and various excipients on the release performance of hydrophilic polyamide 6,10 (PA 6,10) monolithic matrix. Amitriptyline HCl and theophylline were employed as the high and low solubility model drugs, respectively. The incorporation of different excipient concentrations and changes in formulation components influenced the drug release dynamics as evidenced by computed mathematical quantities (t x%, MDT x%, f 1, f 2, k 1, k 2, and К F). The effects of excipients on drug release from the PA 6,10 monolithic matrix was further elucidated using static lattice atomistic simulations wherein the component energy refinements corroborates the in vitro and in silico experimental data. Consequently, the feasibility of modulating release kinetics of drug molecules from the novel PA 6,10 monolithic matrix was well suggested.
亲水基质中的药物释放主要受聚合物侵蚀、解缠、溶解、溶胀前沿移动、药物通过聚合物基质溶解和扩散的调节。这些过程取决于溶解介质、聚合物基质和药物分子之间的相互作用,而这些相互作用可以被配方变量和赋形剂显著影响。本研究利用数学参数来评估所选配方变量和各种赋形剂对亲水聚酰胺 6,10(PA 6,10)整体基质的释放性能的影响。盐酸阿米替林和茶碱分别作为高溶解度和低溶解度模型药物。不同赋形剂浓度的加入和配方成分的变化影响了药物释放动力学,这可以通过计算得到的数学量(t x%、MDT x%、f 1、f 2、k 1、k 2 和 К F)来证明。通过静态晶格原子模拟进一步阐明了赋形剂对 PA 6,10 整体基质中药物释放的影响,其中组分能量细化与体外和计算实验数据相符。因此,从新型 PA 6,10 整体基质中调节药物分子释放动力学的可行性得到了很好的证明。