Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system
Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system
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DOI：
10.1007/s13346-016-0334-7
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发表时间：
2017-01-01
影响因子：
5.4
通讯作者：
Dua, Kamal
中科院分区：
文献类型：
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作者：
Malipeddi, Venkata Ramana;Awasthi, Rajendra;Dua, Kamal
以聚乙烯吡咯烷酮（PVP）和聚乙烯醇（PVA）为原料，研制酒石酸美托洛尔基质型透皮给药系统。对透皮膜进行物理参数评价、傅里叶变换红外光谱分析（FTIR）、差示扫描量热法（DSC）、体外药物释放、体外皮肤渗透性、皮肤刺激试验和稳定性研究。该薄膜坚韧、不粘、易成型，具有良好的抗拉强度。随着pva浓度的增加，膜的抗拉强度也随之增加。FTIR光谱和DSC分析结果显示，药物与聚合物之间没有相互作用。美托洛尔体外释放符合零级动力学，释放机制受扩散速率控制。利用Keshary-Chein（垂直扩散池）对美托洛尔进行体外释放试验，结果表明，24 h内药物释放率为65.5%，24 h外透皮透膜释药率为58.13%，所选制剂的美托洛尔体外透皮动力学为零级。发现其释放机制受扩散速率控制。在为期22天的皮肤刺激试验中，被测透皮膜制剂未出现任何过敏反应、炎症或接触性皮炎。在180天的稳定性研究中，透皮膜表现出良好的稳定性。综上所述，MPT的TDDS有助于绕过首过效应，在不牺牲药物治疗优势的情况下提高患者的依从性。
The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVAwas increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.