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.
We have evaluated the effects of a B2 receptor antagonist (B5630) of kinins on BK and captopril-induced acute hypotensive responses in anaesthetized SHR. Intravenous treatment of BK (1.0 microgram) and captopril (0.3 mg/kg) caused significant (p < 0.05) fall in the SBP and DBP. Whereas BK caused greater fall in the SBP (p < 0.05), DBP (p < 0.01) and duration of hypotension (p < 0.05) when administered after captopril (Fig 1 and 2). All the hypotensive effects of BK and captopril were significantly antagonised (p < 0.05) in the presence of B5630 (2.0 mg/kg). Further, the duration of hypotensive responses of BK and captopril were blocked (p < 0.05) by B5630. The agonists and BK-antagonist did not cause significant (p > 0.05) alterations in HR during the entire investigation. These findings provide evidence to support the suggestion that B2 receptor might be involved in the regulation of the hypotensive actions of BK and captopril. Kinins should also have valuable functions in the antihypertensive property of captopril-like drugs.