Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA.
Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA.
Int J Pharm. 2017 Oct 30;532(1):345-351. doi: 10.1016/j.ijpharm.2017.08.098. Epub 2017 Aug 24.
A liquid crystalline (LC) system, composed of phosphatidylcholine, sorbitan monoleate, and tocopherol acetate, was investigated to understand the in vivo transformation after subcutaneous injection, coupled with the physicochemical and pharmacokinetic properties of the formulation. The rat model was utilized to monitor a pseudo-time course transformation from a precursor LC formulation to the LC matrix, coupled with the blood concentration profiles of the formulations containing leuprolide acetate. Three formulations that result in the H phase, demonstrating dissimilar in vitro release profiles, were used. The formulation showing the highest AUC, C and T, also displayed the greatest release rate in vitro, the lowest viscosity (LC matrix), and an earlier transformation (LC precursor to matrix) in vivo. A potential link between viscosity, phase transformation, and drug release properties of a liquid crystalline system is described.
研究了一种由磷脂酰胆碱、山梨醇单油酸酯和醋酸生育酚组成的液晶（LC）系统，以了解皮下注射后的体内转化，并结合制剂的理化性质和药代动力学性质。利用大鼠模型监测从前体 LC 制剂到 LC 基质的假时程转化，同时监测含有醋酸亮丙瑞林的制剂的血液浓度曲线。使用了三种导致 H 相的制剂，其表现出不同的体外释放曲线。显示 AUC、C 和 T 值最高的制剂在体外也表现出最快的释放速率、最低的粘度（LC 基质）和更早的体内转化（LC 前体到基质）。描述了液晶系统的粘度、相转变和药物释放特性之间的潜在联系。
