Satheeshababu B K, Shivakumar K L
Department of Pharmaceutics, Government College of Pharmacy, #2 P Kalinga Rao Road, Bangalore-560 027, India.
Indian J Pharm Sci. 2013 Mar;75(2):162-70.
The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug.
本研究的目的是通过碳二亚胺介导，将硫醇部分共价连接到阳离子聚合物上，以合成共轭壳聚糖，从而改善壳聚糖的渗透性能。巯基乙酸通过聚合物的伯氨基与巯基乙酸的羧基之间形成酰胺键而共价连接到壳聚糖上。因此，这些聚合物被称为硫醚聚合物或硫醇化聚合物。壳聚糖的共轭通过傅里叶变换红外光谱和差示扫描量热分析得到证实。采用溶剂浇铸技术，使用不同比例的壳聚糖和壳聚糖-巯基乙酸共轭物（2:0、1.7:0.3、1.4:0.6、1:1、0.6:1.4和0.3:1.7）制备了卡维地洛的基质型透皮贴剂。对制备的基质型贴剂进行了理化性质表征，随后进行了体外评价。使用改良的Franz扩散池，对选定的制剂在Wistar白化大鼠皮肤和人体尸体皮肤上进行了离体研究。随着共轭壳聚糖比例的增加，透皮贴剂的药物渗透率增加。药物释放机制为非Fickian型。本研究得出结论，成功开发了使用不同比例壳聚糖的共轭壳聚糖的卡维地洛透皮贴剂，以提高药物渗透率。透皮贴剂可以是一种通过绕过药物广泛的肝脏首过代谢来提高药物生物利用度的良好方法。
