Enhancing permeation of nifedipine transdermal patch by various by surfactants and in vivo evaluation in rabbits

Abstract

Nifedipine transdermal patches were developed by using various types and concentrations of surfactants as permeation enhancers. The preparation composed of 1% W/ W nifedipine, 50% W/W Pluronic F-127, 10% W/W glycerin and 6% W/W Aerosil A 200 was used as control formulation. The good physical appearance formulations were assessed the in vitro skin permeation. The nifedipine transdermal patch with the highest skin permeation amount and rate was selected for in vivo study, using rabbits as animal model comparing with single oral dose administration (Adalat ® 10 mg) . Kinetic parameters included tMAX , CMAX and normalized AUC |0 24 were evaluated. The results from in vitro study indicated that 2% cetyltrimethyl ammonium bromide was a suitable surfactant with providing the highest skin permeation amount whereas 1% cetyltrimethylammonium bromide evidently exhibited the lowest value. Other surfactants showed the difference enhancing effect due to themselves properties. Various concentration of cetylpyridinium chloride were similar to control formulation. For anionic surfactant, preparation composed of 0.5% sodium lauryl sulfate exhibited greater skin permeation amount than other formulations in this group. Increasing concentration of Cremophor A25 decreased nifedipine permeation amount. All nifedipine transdermal systems in this study exhibited, the first phase (0-10 hr), showing the lower nifedipine permeation rate from each formulation involved the process of drug releasing and the effect of skin uptake on the permeation of drug through pig's skin. After that, the permeation rate of the second phase (10-24/28 hours) was higher than the first phase. The selected nifedipine transdermal patch was put on back area of rabbit. It was clearly shown that nifedipine can be released from the transdermal patch into systemic circulation. The nifedipine plasma concentration time profiles of two out from five rabbits showed sustained release pattern of drug from dosage form up to 24 hours. The normalized maximum nifedipine plasma concentration from transdermal patch were relatively less than oral single dose. The significant higher AUC |0 24 of oral nifedipine administration than of transdermal patch was observed. The release pattern of nifedipine from transdermal patch into diffusion cell was highly significant than that release into rabbit circulation. Therefore, It is suggested that transdermal patches have to be improved to get the better released drug in systemic circulation for once a day medication.