镶嵌蒙脱石微球处方前研究及其制备

The preformulation study and preparation of montmorillonite-intercalate microspheres

目的对盐酸倍他洛尔(betaxolol hydrochloride,BH)进行处方前研究,并以丙烯酸树脂为膜材制备载药蒙脱石/丙烯酸树脂微球。方法采用UV和HPLC法考察药物BH的稳定性、表观溶解度、pKa值、亲水亲油平衡值以及pH值对BH离体角膜透过性的影响;以丙烯酸树脂RS和RL为骨架材料,O_1/O_2乳化-溶剂挥发法制备蒙脱石载药缓释微球,扫描电镜观察其形态表征,为处方优化提供依据。结果 BH稳定性良好,在各种溶液中的溶解度为16.30~42.27mg·mL^(-1)。BH为弱碱性药物,pKa值为7.75,角膜透过性受pH值影响,碱性条件下有利于BH的角膜透过。O_1/O_2乳化-溶剂挥发法制备的微球外形圆整,无粘连情况,表面略有粗糙感。结论处方前研究建立的UV-VIS分析方法准确可靠。O_1/O_2乳化-溶剂挥发法可用于制备镶嵌蒙脱石离子交换给药系统。

Objective To research the physical and chemical properties of betaxolol hydrochloride（BH）preformulation.The Eudragit RS/RL 100 was applied as membrane materials in the preparation of drug-loaded montmorillonite microspheres.Methods The model drug BH was determined by UV and HPLC,investigating the stability,apparent solubility,pKa value,hydrophilic lipophilic balance（HLB）of BH and the effect of pH on the in vitro corneal permeability.The drug-loaded montmorillonite microspheres were prepared by O_1/O_2emulsion-solvent evaporation technology,and the morphology of microspheres was characterized by scanning electron micrographs for the prescription optimization.Results The BH had excellent stability.The solubility of BH in various solution was among 16.30-42.27mg·mL^-1.The BH was a weak alkaline molecule with a pKa of 7.75.The pH had a significant influence in the drug corneal permeability,an alkaline conditions would be beneficial to the BH through cornea.The MMT-BH microspheres were prepared by O_1/O_2 emulsion-solvent evaporation technology,and the SEM results showed a spherical and slightly rough surface.Conclusion The UV method to determine the content of betaxolol hydrochloride was accurate and reliable.The O_1/O_2emulsification-solvent evaporation method could be used for the preparation of montmorillonite exchange microspheres.