Amnuaikit Chomchan, Ikeuchi Itsue, Ogawara Ken-Ichi, Higaki Kazutaka, Kimura Toshikiro
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Int J Pharm. 2005 Jan 31;289(1-2):167-78. doi: 10.1016/j.ijpharm.2004.11.007. Epub 2004 Dec 25.
To develop the suitable film formulations of propranolol hydrochloride (PPL) containing enhancers for transdermal use, polymeric film formulations were prepared by employing ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) as a film former, and dibutyl phthalate (DBP) as a plasticizer. Terpenes such as menthol and cineole, and propylene glycol (PG) were also employed as a chemical enhancer to improve the skin penetration of PPL. The film preparations were characterized in physical properties such as uniformity of drug content, thickness and moisture uptake capacity. Release and skin permeation kinetics of PPL from film preparations were examined in the in vitro studies using a Franz-type diffusion cell. The uniformity of drug content was evidenced by the low S.D. values for each film preparation. The moisture uptake capacity and drug release rate increased with the increase of PVP in each preparation. Enhancers examined in the present study also increased the moisture uptake capacity and release rate of PPL from the film preparations. Increasing the concentration of PPL from 1 to 2 mg/cm2 in the film enhanced the release rate of PPL, while no effect of enhancer concentrations on the release rate from the film preparations was observed. In vitro skin permeation study showed that cineole was the most promising enhancer among the enhancers examined in the present study and suggested that the suitable compositions of film preparation would be EC:PVP:PPL=6:3:4 with 10% (w/w) cineole and 7:2:4 with 10% (w/w) PG and cineole, which provided high skin permeation rates at 93.81+/-11.56 and 54.51+/-0.52 microg/cm2/h, respectively.
为开发含渗透促进剂的盐酸普萘洛尔(PPL)透皮用适宜膜剂,以乙基纤维素(EC)和聚乙烯吡咯烷酮(PVP)为成膜材料、邻苯二甲酸二丁酯(DBP)为增塑剂制备了聚合物膜剂。还使用薄荷醇和桉叶油等萜类化合物以及丙二醇(PG)作为化学渗透促进剂来提高PPL的皮肤渗透能力。对膜剂的物理性质如药物含量均匀度、厚度和吸湿能力进行了表征。使用Franz型扩散池在体外研究中考察了PPL从膜剂中的释放和皮肤渗透动力学。每种膜剂的低标准差数值证明了药物含量的均匀度。每种制剂中吸湿能力和药物释放速率随PVP的增加而提高。本研究中考察的渗透促进剂也提高了PPL从膜剂中的吸湿能力和释放速率。膜剂中PPL浓度从1mg/cm²增加到2mg/cm²可提高PPL的释放速率,而未观察到渗透促进剂浓度对膜剂释放速率有影响。体外皮肤渗透研究表明,在本研究考察的渗透促进剂中桉叶油是最有前景的,还表明适宜的膜剂组成为EC:PVP:PPL = 6:3:4并含10%(w/w)桉叶油以及7:2:4并含10%(w/w)PG和桉叶油,它们分别提供了93.81±11.56和54.51±0.52μg/cm²/h的高皮肤渗透速率。