阿托伐他汀钙自微乳给药系统的制剂及体外评价。

Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Izmir, Turkey.

Ege University, Center For Drug Research & Development and Pharmacokinetic Applications (ARGEFAR), Izmir, Turkey.

Curr Drug Deliv. 2019;16(8):768-779. doi: 10.2174/1567201816666190820143957.

OBJECTIVE

The aim of this study was to develop a new dosage form as an alternative to the classical tablet forms of atorvastatin calcium (AtrCa). The formulation strategy was to prepare an optimum self micro emulsifying drug delivery system (SMEDDS) to overcome the problem of low solubility of the active substance.

METHODS

In this study, pseudo ternary phase diagrams were plotted determined by the solubility studies. According to the solubility studies; oleic acid was used as the oil phase, Tween 20 and Span 80 were used as the surfactants and ethanol was used as the co-surfactant. SMEDDS formulations were characterized according to pH, electrical conductivity, density, refractive index, viscosity, emulsification time, dispersibility, robustness of dilution stability, droplet size, polidispersity index, zeta potential, transmittance %, cloud point, content quantification %, chemical and physical stability. The lipolysis study was conducted under fed and fasted conditions. In vitro release studies and kinetic evaluation were carried out. Permeability studies were also examined with Caco-2 cell culture.

RESULTS

The droplet size of the optimized formulation did not change significantly in different medias over the test time period. Improved SMEDDS formulation will progress steadily without precipitating along the gastrointestinal tract. Lipolysis studies showed that the oil solution had been exposed to high amount of lipolysis compared to the SMEDDS formulation. The release rate of AtrCa from AtrCa- SMEDDS formulation (93.8%, at 15 minutes) was found as increased when the results were compared with commercial tablet formulation and pure drug. The permeability value of AtrCa from AtrCa- SMEDDS formulation was found higher than pure AtrCa and commercial tablet formulation, approximately 9.94 and 1.64 times, respectively.

CONCLUSION

Thus, lipid-based SMEDDS formulation is a potential formulation candidate for lymphatic route in terms of the increased solubility of AtrCa.

目的

本研究旨在开发一种新剂型，作为阿托伐他汀钙（AtrCa）经典片剂的替代剂型。该制剂策略是制备最佳自微乳药物传递系统（SMEDDS），以克服活性物质溶解度低的问题。

方法

在这项研究中，通过溶解度研究绘制伪三元相图。根据溶解度研究，油酸被用作油相，吐温 20 和司盘 80 被用作表面活性剂，乙醇被用作助表面活性剂。SMEDDS 制剂根据 pH 值、电导率、密度、折射率、粘度、乳化时间、分散性、稀释稳定性的稳健性、粒径、多分散指数、zeta 电位、透光率%、浊点、含量定量%、化学和物理稳定性进行了表征。在进食和禁食条件下进行了脂肪分解研究。进行了体外释放研究和动力学评价。还通过 Caco-2 细胞培养检查了渗透性研究。

结果

优化配方的粒径在测试时间段内不会在不同介质中发生显著变化。改进的 SMEDDS 制剂将在整个胃肠道中稳定地进展，而不会沉淀。脂肪分解研究表明，与 SMEDDS 制剂相比，油溶液已经暴露于大量的脂肪分解中。与商业片剂制剂和纯药物相比，AtrCa-SMEDDS 制剂中 AtrCa 的释放速率（15 分钟时为 93.8%）发现有所增加。AtrCa-SMEDDS 制剂中 AtrCa 的渗透性值被发现高于纯 AtrCa 和商业片剂制剂，分别约为 9.94 倍和 1.64 倍。