Development of matrix type transdermal patches of lercanidipine hydrochloride: physicochemical and in-vitro characterization.

OBJECTIVE

Lercanidipine hydrochloride (LRDP) is used in the treatment of hypertension because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS) of LRDP and to determine the effect of penetration enhancer, limonene on drug permeation

METHODS

The matrix type TDDS of LRDP were prepared by solvent evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of Eudragit RL100 (ERL) and hydroxypropyl methyl cellulose (HPMC) in 1.5:8.5, 3:7, 4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried 10 mg of LRDP/patch area, 8% v/w of d-limonene as a penetration enhancer, 20% v/w of propylene glycol as plasticizer in methanol and dichloromethane as solvent system. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation studies were carried out across excised rat skin using Franz diffusion cell.

RESULTS

All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 24 hrs from the six formulations were 82.0%, 74.9%, 63.2%, 63.5%, 59.8% and 53.5% respectively. Corresponding values for the cumulative amounts of the drug permeated across the rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5 and 1663.4 µg/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of the drug release was diffusion mediated. The patches were seemingly free of potentially hazardous skin irritation.

CONCLUSIONS

The patches composed of ERL, HPMC (1.5:8.5) with 8% v/w limonene as penetration enhancer may be selected for the development of TDDS of LRDP for potential therapeutic use by using a suitable adhesive layer and backing membrane.