Design and in vivo pharmacokinetic study of a newly developed lamivudine transdermal patch

Abstract

The aim of this study was to formulate a soft and easy to handle matrix-type transdermal patch consisting of a simple and cost-effective monolithic polymeric film as an attempt to deliver lamivudine (LAM) transdermally and overcome the problems associated with its biological short half-life and fluctuations in plasma concentration upon oral administration.First, LAM-polymer compatibilities between LAM and three polymers; methylcellulose (MC), sodium alginate (SA) and chitosan (CS) were studied using Fourier transform infrared (FT-IR) and differential scanning calomerty (DSC). Placebo polymeric monolithic films were prepared using MC, SA and CS as the polymers and glycerin, propylene glycol (PG) and polyethylene glycol 400 (PEG400) as plasticizers. Then, the organoleptic properties of the films were examined. Using glycerin, medicated monolithic films (25 mg LAM each) were prepared and their physicochemical properties were determined. Matrix-type transdermal patches were fabricated using the medicated films as drug supply layers. The patches were evaluated for their ex vivo permeation. Male Spargue-Dawley rats were used for in vivo pharmacokinetic comparative study between MC-based matrix-type transdermal patches and oral LAM solution and the pharmacokinetic parameters were calculated.Drug-polymer compatibility studies ruled out the possibility of interaction between LAM and the selected polymers. Based on the organoleptic properties, glycerin was selected as a plasticizer. Among the tested films, the glycerin-plasticized MC films had acceptable physicochemical properties. The MC-based matrix-type transdermal patches showed the highest steady state flux, the highest permeability coefficient and the highest cumulative amount of LAM permeated without appearance of lag time. The transdermal patches enhanced the pharmacokinetic parameters of LAM. They exhibited absence of the high fluctuations of LAM plasma concentration and increasing the biological half-life by about 40 folds.It was concluded that the MC-based transdermal patches could serve as a potential innovative drug delivery system of LAM for sustained transdermal delivery as an alternative to the conventional oral approaches. Keywords: Lamivudine, Innovative, Polymer, Design, Transdermal patches, Matrix, ex vivo, In vivo, Rat, Pharmacokinetic parameters