Formulation design and in vitro ex vivo evaluation of transdermal patches of Cinnarizine.

The aim of this study was to develop a Transdermal patch containing Cinnarizine using different ratios of hydrophilic and hydrophobic polymeric systems by solvent evaporation technique employing Polyethylene glycol (PEG 400) as plasticizer. The physicochemical compatibility of the drug and the polymers were studied by performing FT-IR spectroscopic analysis. Formulated patches were evaluated for physicochemical properties, skin irritation, in vitro drug release, ex-vivo permeation studies across rat abdominal skin and stability studies. The results of FT-IR studies revealed that there were no interactions between drug and polymers used. All the formulations exhibited uniformity in physicochemical properties. In vitro permeation studies of the formulations were performed by using Franz diffusion cells. Formulation F3 showed better permeation through rat skin (i.e., 8527.5±1.25µ/cm2 /hr) compared to rest of formulations and followed Fick's diffusion mechanism. On the basis of in-vitro drug release and ex-vivo skin permeation performance, Formulation F3 containing the polymeric blend 19:1 Hydroxypropylmethyl Cellulose (HPMC E 50cps: Eudragit RL 100) has shown optimum release in comparison to other formulations and indicated good physical stability. So it has been demonstrated that Cinnarizine can be designed as matrix type transdermal drug delivery system (TDDS) and further in-vivo evaluations were required.

Effect of pomegranate juice on intestinal transport and pharmacokinetics of nitrendipine in rats.

Pomegranate juice (PJ) is known to be a potent inhibitor of human cytochromes (CYP), particularly CYP2C9 and CYP3A4. The purpose of this study was to investigate the effect of oral PJ on the pharmacokinetics of nitrendipine (10 mg/kg) in rats. The effect of PJ was also investigated on the absorption kinetics of nitrendipine in rats using a single-pass intestinal perfusion model. There was a significant increase in effective permeability, absorption rate constant and fraction of drug absorbed in the pretreated group when compared with the control group, probably due to inhibition of the P-glycoprotein-mediated efflux of the drug by PJ. In comparison with control, PJ treatment significantly increased the area under the concentration-time curve of oral nitrendipine. The peak plasma concentration of nitrendipine was also significantly increased by PJ. However, elimination half-life of nitrendipine was not altered significantly in both PJ co-administered and pretreated groups. These results suggest that PJ inhibits the intestinal metabolism of nitrendipine without inhibiting the hepatic metabolism in rats. Therefore, the concomitant use of PJ, as food supplement, and nitrendipine should be avoided, although further clinical studies need to be undertaken in order to confirm this finding.