a Department of Pharmaceutical Technology , AU College of Pharmaceutical Sciences, Andhra University , Visakhapatnam , India.
b Aditya Pharmacy College , Surampalem , India.
Drug Dev Ind Pharm. 2019 Apr;45(4):548-559. doi: 10.1080/03639045.2019.1567758. Epub 2019 Feb 3.
Self-emulsifying drug delivery systems (SES) were developed to improve oral bioavailability of asenapine maleate (ASM), an antipsychotic drug with challenging amphiphobic nature and extensive pre-systemic metabolism. ASM-SES was prepared by choosing the proportion of oil, surfactant, co-surfactant from constructed phase diagram. The in vitro and ex vivo evaluation was done. In vivo evaluation was done through pharmacokinetic and pharmacodynamic studies. Role of lymphatic absorption was studied by lymphatic absorption inhibition study. A formulation consisting of 9.9%, 59.4%, 29.7% and 1% of oil, surfactant, co-surfactant, and drug respectively was considered as optimized formulation. After various evaluation test, the globule size and zeta potential for optimized formulation (SES) were found to be 137.9 nm and -28.8 mV respectively. A maximum of 99.64 ± 0.16% of ASM was released from SES in 60 minutes of time. The flux (ex vivo study) increased by 2.33 folds, which prove the enhanced release and permeation of ASM when loaded into SES. The animals administered with SES showed higher activity and good pharmacodynamic response than the control and ASM-Suspension, which may be due to the greater availability of the drug. The maximum pharmacodynamic response was observed at the t determined by Pharmacokinetic studies. The bioavailability increased by 1.64 folds with 16.55 ± 3.11% as extend of lymphatic absorption (r = 0.9732). Good in vitro in vivo correlation was observed. ASM-SES is a novel approach to effectively deliver ASM and improve the oral bioavailability.
自乳化药物传递系统 (SES) 的开发旨在提高马来酸阿散平 (ASM) 的口服生物利用度，ASM 是一种具有挑战性的两亲性和广泛的前体系统代谢的抗精神病药物。通过从构建的相图中选择油、表面活性剂、助表面活性剂的比例来制备 ASM-SES。进行了体外和离体评价。通过药代动力学和药效学研究进行了体内评价。通过淋巴吸收抑制研究研究了淋巴吸收的作用。包含 9.9%、59.4%、29.7%和 1%的油、表面活性剂、助表面活性剂和药物的制剂被认为是优化的制剂。经过各种评价试验，优化制剂 (SES) 的粒径和 Zeta 电位分别为 137.9nm 和-28.8mV。SES 中 ASM 的最大释放量在 60 分钟内达到 99.64±0.16%。通量（离体研究）增加了 2.33 倍，这证明了 ASM 载入 SES 后释放和渗透得到了增强。与对照和 ASM 混悬剂相比，给予 SES 的动物表现出更高的活性和良好的药效反应，这可能是由于药物的可用性更高。在药代动力学研究确定的 t 时观察到最大药效反应。生物利用度增加了 1.64 倍，淋巴吸收扩展度为 16.55±3.11%（r=0.9732）。观察到良好的体外-体内相关性。ASM-SES 是一种有效传递 ASM 和提高口服生物利用度的新方法。
