Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
Department of Pharmacy, Faculty of Pharmacy, Mutah University, Karak, Jordan.
AAPS PharmSciTech. 2020 May 20;21(5):146. doi: 10.1208/s12249-020-01683-3.
The objective of this work was to study the effect of the physiologically relevant enzymes pepsin, pancreatin, and the synthetic surfactant sodium lauryl sulfate (SLS) on the surface tension of the dissolution media and the solubility and dissolution of the weakly basic drug carvedilol. Compendial dissolution media and buffer solutions that simulate the gastrointestinal fluid, prepared with and without the addition of SLS, were used in this study. The surface tension of the dissolution media; critical micelle concentration (CMC) of SLS in buffer solutions; and size, polydispersity index, and zeta potential of SLS micelles loading carvedilol were determined. The solubility and dissolution of carvedilol were investigated and compared with those of the corresponding media prepared without the addition of pepsin, pancreatin, and SLS. Results showed that the addition of pepsin, pancreatin, and SLS lowered the surface tension of the dissolution media to 54.8, 55.7, and ~ 30 mN/m, respectively. The solubility of carvedilol was significantly enhanced with pepsin and SLS; however, no significant difference was found with pancreatin. The dissolution rate of carvedilol was fast in simulated gastric fluid with and without pepsin. The dissolution was further enhanced in media with pancreatin and SLS. The dissolution data were corroborated with the molar micellar solubilization (X) of SLS, ranging between 0.02 and 3.09. Understanding the effect of pepsin, pancreatin, and SLS on the surface tension of the dissolution media and the solubility and dissolution of poorly soluble drugs can improve our knowledge of the performance of these drugs in vivo.
本工作旨在研究生理相关酶胃蛋白酶、胰蛋白酶和合成表面活性剂十二烷基硫酸钠（SLS）对溶解介质表面张力、弱碱性药物卡维地洛溶解度和溶解的影响。本研究使用了药典溶解介质和模拟胃肠液的缓冲溶液，分别制备了添加和不添加 SLS 的溶液。测定了溶解介质的表面张力；缓冲溶液中 SLS 的临界胶束浓度（CMC）；以及载有卡维地洛的 SLS 胶束的粒径、多分散指数和 Zeta 电位。考察了卡维地洛的溶解度和溶解情况，并与未添加胃蛋白酶、胰蛋白酶和 SLS 的相应介质进行了比较。结果表明，添加胃蛋白酶、胰蛋白酶和 SLS 可将溶解介质的表面张力分别降低至 54.8、55.7 和~30 mN/m。卡维地洛的溶解度随胃蛋白酶和 SLS 的添加而显著提高，但与胰蛋白酶的添加相比无显著差异。卡维地洛在有胃蛋白酶和无胃蛋白酶的模拟胃液中的溶解速度很快。在含有胰蛋白酶和 SLS 的介质中进一步增强了溶解。溶解数据与 SLS 的摩尔胶束增溶度（X）相符，范围在 0.02 至 3.09 之间。了解胃蛋白酶、胰蛋白酶和 SLS 对溶解介质表面张力、难溶性药物溶解度和溶解的影响，有助于加深我们对这些药物在体内性能的认识。
