含泼尼松龙的藻酸盐/壳聚糖微粒的制备及其黏膜黏附性能的体外评价

Preparation and in vitro evaluation of mucoadhesive properties of alginate/chitosan microparticles containing prednisolone.

作者信息

Wittaya-areekul Sakchai, Kruenate Jittiporn, Prahsarn Chureerat

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.

出版信息

Int J Pharm. 2006 Apr 7;312(1-2):113-8. doi: 10.1016/j.ijpharm.2006.01.003. Epub 2006 Feb 21.

DOI:10.1016/j.ijpharm.2006.01.003

PMID:16490331

Abstract

This study describes the preparation of mucoadhesive alginate/chitosan microparticles containing prednisolone intended for colon-specific delivery. Two methods have been used for the preparation of the particles: the one-step method is the method in which prednisolone was dispersed within sodium alginate solution and this dispersion was then dropped in a solution containing both calcium chloride and chitosan. The two-step method consisted also of the dispersion of prednisolone in alginate solution and then dropping this dispersion into a solution containing calcium chloride, the particles were then transferred to a chitosan solution. The concentration of sodium alginate solution at 2% (w/v), various concentrations of calcium chloride solution (0.5-1.0%, w/v), chitosan solutions (0.5, 1.0 and 1.5%, w/v) and prednisolone drug load (2, 5, 10 and 15%, w/v) have been used. The results for both preparation methods show that the particle size and drug content were mainly depending on the amount of the drug concentration and not the amount of chitosan and calcium chloride. The in vitro mucoadhesive tests for particles prepared from both methods were carried out using the freshly excised gut of pigs. The particles prepared by the one-step method exhibited excellent mucoadhesive properties after 1h test. Increased chitosan concentrations from 0, 0.5, 1.0 to 1.5% (w/v) resulted in 43, 55, 82 and 88% of the particle remaining attached on the gut surface after 1 h, respectively. However, the particles prepared by the two-step method showed significant less mucoadhesion under the same experimental conditions. At chitosan concentrations of 0, 0.5, 1.0 and 1.5% (w/v) the amount of particles remaining attached to the mucosal surface of the pig gut after 1 h was 43, 3, 11 and 11%, respectively. The prednisolone release at a pH of 6.8 after 4 h was between 63 and 79% for the particles prepared by the one-step method and between 57 and 88% for the particles prepared by the two-step method with a prednisolone drug load of 5 and 10% (w/v), respectively. The results show that depending on the preparation method these chitosan coated alginate particles show different mucoadhesiveness whereas their other properties are not statistically significant different.

摘要

本研究描述了用于结肠特异性给药的含泼尼松龙的粘膜粘附性海藻酸盐/壳聚糖微粒的制备。制备微粒使用了两种方法：一步法是将泼尼松龙分散在海藻酸钠溶液中，然后将此分散液滴入含有氯化钙和壳聚糖的溶液中。两步法同样是先将泼尼松龙分散在海藻酸盐溶液中，然后将此分散液滴入含有氯化钙的溶液中，接着将微粒转移至壳聚糖溶液中。使用了2%（w/v）的海藻酸钠溶液浓度、不同浓度的氯化钙溶液（0.5 - 1.0%，w/v）、壳聚糖溶液（0.5%、1.0%和1.5%，w/v）以及泼尼松龙载药量（2%、5%、10%和15%，w/v）。两种制备方法的结果均表明，粒径和药物含量主要取决于药物浓度，而非壳聚糖和氯化钙的用量。使用刚切除的猪肠道对两种方法制备的微粒进行了体外粘膜粘附试验。一步法制备的微粒在1小时试验后表现出优异的粘膜粘附性能。壳聚糖浓度从0、0.5%、1.0%增加至1.5%（w/v）时，1小时后分别有43%、55%、82%和88%的微粒仍附着在肠道表面。然而，在相同实验条件下，两步法制备的微粒显示出显著较低的粘膜粘附性。壳聚糖浓度为0、0.5%、1.0%和1.5%（w/v）时，1小时后附着在猪肠道粘膜表面的微粒量分别为43%、3%、11%和11%。对于载药量分别为5%和10%（w/v）的一步法制备的微粒，在pH 6.8条件下4小时后的泼尼松龙释放率在63%至79%之间，两步法制备的微粒的释放率在57%至88%之间。结果表明，取决于制备方法，这些壳聚糖包衣的海藻酸盐微粒表现出不同的粘膜粘附性，而它们的其他性质在统计学上无显著差异。