In vitro and In vivo characterization of the transdermal delivery of sertraline hydrochloride Films

Abstract

Background and the purpose of the study: Sertraline hydrochloride is a selective serotonin reuptake inhibitor principally used in the treatment of major depressive disorder. To maintain the therapeutic plasma drug concentration of the drug for prolonged period, the transdermal drug delivery has been chosen as an alternative route of drug delivery. The pharmacokinetic properties of sertraline hydrochloride make it suitable for transdermal delivery. The purpose of the study was to investigate the effect of polymers and penetration enhancers on the transdermal delivery of the drug in order to improve its therapeutic efficacy.

Methods: In the preparation of films, Eudragit RL 100, Eudragit RS 100, hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose were used as polymers. The films were characterized for thickness, tensile strength, drug content, moisture uptake, moisture content, water vapor transmission rate and drug release. The films exhibiting higher rates of drug release were subjected to study the effect of oleic acid and propylene glycol as penetration enhancers on skin permeation of sertraline hydrochloride. In vivo and skin irritation studies were performed for the optimized film.

Results: Films containing Eudragit RL 100, Eudragit RL 100 and HPMC showed the highest drug release of 94.34% and 96.90% respectively in a period of 42 hrs. The release data fitted into kinetic equations, yielded zero-order and fickian mechanism of drug release. There was a two-fold increase in skin permeation of sertraline hydrochloride in the presence of penetration enhancers in the film. The physical evaluation indicated the formation of smooth, flexible and translucent films. No skin irritation occurred on rabbit skin and the infrared studies showed the compatibility of the drug with the formulation excipients. The in vivo study revealed a constant plasma concentration of drug for long periods and the films containing penetration enhancers had achieved adequate plasma levels of the drug.

Conclusions: The obtained results indicated the feasibility for transdermal delivery of sertraline hydrochloride using eudragit RL 100 and HPMC.

Keywords: Antidepressant; Ethyl Cellulose; Eudragit; Hydroxy Propyl Methyl Cellulose; In-Vitro and In-Vivo Skin Permeation.

Figure 1

FTIR spectra of the drug (A) , drug and Eudragit RL 100 (B), drug and Eudragit RS 100 (C), drug and HPMC (D) and drug and EC (E).

Figure 2

In vitro drug release of sertraline hydrochloride transdermal films F1-F8.

Figure 3

Comparative in vitro skin permeation profile of sertraline hydrochloride and its transdermal films.

Figure 4

Rabbit skin before (A) and after (B) skin irritation test.

Figure 5

Plasma drug concentration profile of sertraline hydrochloride after oral and transdermal administration (film F3, film F3 with penetration enhancers).