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含盐酸普萘洛尔的聚合物膜用于透皮给药的药物释放动力学

Drug release kinetics from polymeric films containing propranolol hydrochloride for transdermal use.

作者信息

Rao P R, Ramakrishna S, Diwan P V

机构信息

Pharmacology Division, India Institute of Chemical Technology, Hyderabad, India.

出版信息

Pharm Dev Technol. 2000;5(4):465-72. doi: 10.1081/pdt-100102030.

Abstract

Polymeric films containing propranolol hydrochloride (PPN) were formulated and evaluated with a view to select a suitable formulation for the development of transdermal drug delivery systems. Films containing different ratios of ethyl cellulose (EC), poly(vinylpyrrolidone) (PVP), and PPN were prepared by mercury substrate method. In vitro drug release and skin permeation studies were conducted using paddle over disk and modified Franz diffusion cell, respectively. The drug release profiles from the polymeric film indicated that the drug content in the film decreased at an apparent first-order rate, whereas the quantity of drug release was proportional to the square root of time. The release rate of PPN increased linearly with increasing drug concentration and PVP fraction in the film, but was found to be independent of film thickness. The increase in release rate may be due to leaching of hydrophilic fraction of the film former, which resulted in the formation of pores. It was also observed that the release of drug from the films followed the diffusion-controlled model at low drug concentration. A burst effect was observed initially, however, at high drug loading level, which may be due to rapid dissolution of the surface drug followed by the diffusion of the drug through the polymer network in the film. The in vitro skin permeation profiles displayed increased flux values with increase of initial drug concentration in the film, and also with the PVP content. From this study, it is concluded that the films composed of EC/PVP/PPN, 9:1:3, 8:2:2, and 8:2:3, should be selected for the development of transdermal drug delivery systems using a suitable adhesive layer and backing membrane for potential therapeutic applications.

摘要

制备并评估了含有盐酸普萘洛尔(PPN)的聚合物薄膜,目的是选择一种合适的制剂用于透皮给药系统的开发。采用汞衬底法制备了含有不同比例乙基纤维素(EC)、聚乙烯吡咯烷酮(PVP)和PPN的薄膜。分别使用桨碟法和改良的Franz扩散池进行了体外药物释放和皮肤渗透研究。聚合物薄膜的药物释放曲线表明,薄膜中的药物含量以明显的一级速率下降,而药物释放量与时间的平方根成正比。PPN的释放速率随薄膜中药物浓度和PVP比例的增加而线性增加,但与薄膜厚度无关。释放速率的增加可能是由于成膜材料亲水性部分的浸出,从而导致孔隙的形成。还观察到,在低药物浓度下,药物从薄膜中的释放遵循扩散控制模型。最初观察到有突释效应,然而,在高载药量水平下,这可能是由于表面药物的快速溶解,随后药物通过薄膜中的聚合物网络扩散所致。体外皮肤渗透曲线显示,随着薄膜中初始药物浓度的增加以及PVP含量的增加,通量值也增加。从这项研究可以得出结论,应由EC/PVP/PPN(9:1:3、8:2:2和8:2:3)组成的薄膜,应选择用于开发透皮给药系统,并使用合适的粘合剂层和背衬膜用于潜在的治疗应用。

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