Development of carvedilol transdermal patches: evaluation of physicochemical, ex vivo and mechanical properties

Abstract

Monolithic matrix-type transdermal drug delivery systems for carvedilol were prepared using a film casting technique involving hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), Eudragit RS 100 (ERS 100), and Eudragit RL 100 (ERL 100) as matrix-forming polymers. The prepared transdermal drug delivery systems were extensively evaluated for in vitro release, ex vivo permeation through rat abdominal skin, moisture absorption, moisture content, water vapor transmission, stability, and mechanical properties. Formulations F2, F3, and F5 were composed of a 4:1 ratio of HPMC, ERS 100; HPMC, HPC; and HPMC, ERL 100, respectively, whereas F4, F6, and F7 were composed of 3:0.5:0.5 of HPMC, ERS 100, HPC; HPMC, HPC, ERL 100; and HPMC, ERS 100, ERL 100. Formulation F1 was composed of HPMC polymer. All formulations carried 8% v/w of d-limonene as a penetration enhancer and 20% v/w of dibutylphthalate as a plasticizer. The physicochemical interaction between carvedilol and polymers were investigated by Fourier transform infrared spectroscopy and differential scanning calorimetry. Formulation F5 showed both maximum drug release (12.31 mg) and permeation (2987.67 microg/cm2) in 24 h, which differed significantly (P < 0.05) among all the formulations. Formulation F5 showed maximum flux (32.80 microg/h/cm2), which meets the flux requirements, and differed significantly (P < 0.05) among all the formulations with a permeation coefficient of 0.82 x 10(-2) cm/h. Fourier transform infrared spectroscopy and differential scanning calorimetry studies showed no evidence of interaction between the drug and polymers. The formulations mechanical properties, tensile strength and elastic modulus (5.89 kg/cm2 for formulation F5) reveal that they are strong but not brittle. A shelf life of 2 years was predicted for the transdermal drug delivery systems. Carvedilol monolithic matrix-type transdermal therapeutic systems could be prepared having both the required flux and suitable mechanical properties.