Nair Rajesh Sreedharan, Nair Sujith
Faculty of Pharmaceutical Sciences, UCSI University, No.1, Jalan Menara Gading, UCSI Heights, Cheras 56000, Kuala Lumpur, Malaysia.
Curr Drug Deliv. 2015;12(5):517-23. doi: 10.2174/1567201812666150212124508.
Mortality rate due to heart diseases increases dramatically with age. Captopril is an angiotensin converting enzyme inhibitor (ACE) used effectively for the management of hypertension. Due to short elimination half-life of captopril the oral dose is very high. Captopril is prone to oxidation and it has been reported that the oxidation rate of captopril in skin tissues is considerably low when compared to intestinal tissues. All these factors make captopril an ideal drug candidate for transdermal delivery. In this research work an effort was made to formulate transdermal films of captopril by utilizing polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) as film formers and polyethylene glycol 400 (PEG400) as a plasticizer. Dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) were used as permeation enhancers. Physicochemical parameters of the films such as appearance, thickness, weight variation and drug content were evaluated. The invitro permeation studies were carried out through excised human cadaver skin using Franz diffusion cells. The in-vitro permeation studies demonstrated that the film (P4) having the polymer ratio (PVP:PVA = 80:20) with DMSO (10%) resulted a promising drug release of 79.58% at 24 hours with a flux of 70.0 µg/cm(2)/hr. No signs of erythema or oedema were observed on the rabbit skin as a result of skin irritation study by Draize test. Based on the stability report it was confirmed that the films were physically and chemically stable, hence the prepared films are very well suited for transdermal application.
心脏病死亡率随年龄急剧上升。卡托普利是一种血管紧张素转换酶抑制剂（ACE），可有效用于治疗高血压。由于卡托普利的消除半衰期短，口服剂量非常高。卡托普利易于氧化，据报道，与肠道组织相比，卡托普利在皮肤组织中的氧化速率相当低。所有这些因素使卡托普利成为经皮给药的理想候选药物。在这项研究工作中，努力利用聚乙烯吡咯烷酮（PVP）和聚乙烯醇（PVA）作为成膜剂，聚乙二醇400（PEG400）作为增塑剂来制备卡托普利的透皮膜。二甲基亚砜（DMSO）和二甲基甲酰胺（DMF）用作渗透促进剂。评估了膜的外观、厚度、重量变化和药物含量等物理化学参数。使用Franz扩散池通过切除的人体尸体皮肤进行体外渗透研究。体外渗透研究表明，聚合物比例为（PVP:PVA = 80:20）且含有10% DMSO的膜（P4）在24小时时的药物释放率为79.58%，通量为70.0 µg/cm²/hr，前景良好。通过Draize试验进行的皮肤刺激性研究结果显示，兔皮肤上未观察到红斑或水肿迹象。根据稳定性报告，证实该膜在物理和化学上是稳定的，因此所制备的膜非常适合经皮应用。
