University Institute of Pharmaceutical Sciences (UGC Centre of Advanced Studies), Panjab University, Chandigarh 160 014, India.
Curr Drug Deliv. 2009 Oct;6(5):495-504. doi: 10.2174/156720109789941669.
Phase-sensitive in situ gel forming controlled release formulations of cyclosporine were prepared using poly (lactide-co-glycolide) and a solvent system consisting of various proportions of benzyl benzoate and benzyl alcohol. Uniformity of content of cyclosporine in the formulation and in vitro release samples was determined by radio immune assay (RIA). FTIR and CD spectroscopy ratified the conformational stability of cyclosporine in the formulation and in vitro release samples, respectively. Rheological properties of the formulations, assessed under isothermal conditions, showed dilatant behavior of all the formulations. In vivo studies were carried out on the optimized formulations vis-à-vis pure cyclosporine in rats and drug levels were monitored for 13 days. Mean plasma concentration of cyclosporine was calculated for all the animals and pharmacokinetic parameters were determined using Win NonLin software. The studies construed better regulation of plasma drug levels with the optimized formulation vis-à-vis routine once-a-day administration of cyclosporine. The subcutaneous tissues, further subjected to histopathological examinations ascertained the biocompatibility of the formulation.
采用聚（乳酸-共-乙醇酸）和由不同比例的苯甲酸苄酯和苄醇组成的溶剂系统，制备了环孢素的相敏原位凝胶形成控释制剂。通过放射免疫测定（RIA）测定制剂和体外释放样品中环孢素的含量均匀度。傅里叶变换红外光谱（FTIR）和圆二色光谱（CD 光谱）分别证实了环孢素在制剂和体外释放样品中的构象稳定性。在等温条件下评估制剂的流变性质，所有制剂均表现出膨胀行为。在大鼠身上对优化的制剂进行了体内研究，并与纯环孢素进行了比较，监测了 13 天的药物水平。对所有动物计算了环孢素的平均血浆浓度，并使用 Win NonLin 软件确定了药代动力学参数。研究表明，与常规的每日一次的环孢素给药相比，优化的制剂能够更好地控制血浆药物水平。进一步对皮下组织进行组织病理学检查，确定了制剂的生物相容性。
