Development of Matrix-Type Transdermal Delivery of Lornoxicam: In Vitro Evaluation and Pharmacodynamic and Pharmacokinetic Studies in Albino Rats

Abstract

A matrix-type transdermal drug delivery system of lornoxicam was prepared with the addition of combination of hydrophilic and hydrophobic polymers in different ratios. Transdermal patches of lornoxicam were designed with ethyl cellulose:polyvinylpyrrolidone and Eudragit RL 100:Eudragit RS 100 in different ratios with propylene glycol as plasticizer (5%) and tween 80 as permeation enhancer using the solvent evaporation technique. Evaluation of these formulations was performed through mechanical characterization and in vitro permeation studies. From the physicochemical and in vitro permeation data, the two formulations showing the best result (A3 and B3) were selected for further in vivo studies. The anti-inflammatory and analgesic effects of the patches were studied using the carrageenan paw edema model and hot plate test, respectively. The pharmacokinetic parameters were studied and recorded on animals. Formulations A3 and B3 exhibited greatest (311.04 μg and 306.32 μg, respectively) cumulative amount of drug release. The Higuchi model seemed to be the most appropriate model describing release kinetics from all patches (r² = 0.9847–0.9971). It was observed that both the patches significantly controlled inflammation and showed analgesic effect from the first hour (P < 0.05). Formulations A3 and B3 were found to enhance the bioavailability of lornoxicam by 3.1 and 2.7 times, respectively, with reference to the oral dosage form. Hence, lornoxicam can be formulated into transdermal patches to sustain its release characteristics and to avoid the disadvantages of oral routes. Formulations A3 and B3 were found to be the best choice to manufacture a lornoxicam transdermal drug delivery system.

LAY ABSTRACT: The objective of the present work was to develop a matrix-type transdermal drug delivery system of lornoxicam with the addition of ethyl cellulose:polyvinylpyrrolidone and Eudragit RL 100:Eudragit RS 100 in different ratios with propylene glycol as plasticizer (5%) and tween 80 as permeation enhancer using the solvent evaporation technique. Lornoxicam is a non-steroidal anti-inflammatory drug that is used for the treatment of pain, inflammation, and arthritis. The prepared patches were evaluated for mechanical characterization and in vitro permeation studies. The formulations showing best results (A3 and B3) were selected further for in vivo and pharmacokinetic studies on animals. From the results, it was found that formulations A3 and B3 exhibited greatest cumulative amount of drug release, controlled inflammation, and showed analgesic effect from the first hour. Hence, lornoxicam can be formulated into transdermal patches, and formulations A3 and B3 were found to be the best choice to manufacture a lornoxicam transdermal drug delivery system.