Development and evaluation of carvedilol transdermal patches

Abstract

Carvedilol is a novel, multiple-action cardiovascular drug that is currently approved in many countries for the treatment of hypertension. The reduction in blood pressure produced by carvedilol results primarily from beta-adrenoceptor blockade and vasodilation, the latter resulting from alpha 1-adrenoceptor blockade. These actions as well as several other carvedilol activities are associated with cardioprotection in animal models that occurs to a degree that is greater than that observed with other drugs. The multiple actions of carvedilol may also provide the underlying rationale for the use of the drug in the treatment of coronary artery disease and congestive heart failure (1).Carvedilol is well absorbed from the gastrointestinal tract but is subject to considerable first-pass metabolism in the liver; its absolute bioavailability is about 25%. It has a half-life of 2.2 ± 0.3 h; longer half-lives of about 6 h have been measured at lower concentrations (2, 3). Transdermal patches of carvedilol with a HPMC-drug reservoir were prepared by the solvent evaporation technique. In this investigation, the membranes of Eudragit RL100 and Eudragit RS100 were cast to achieve controlled release of the drug. The prepared patches possessed satisfactory physicochemical characteristics. Thickness, mass and drug content were uniform in prepared batches. Moisture vapour transmission through the patches followed zero-order kinetics. In vitro permeation studies were performed using a K-C diffusion cell across hairless guinea pig skin and followed the super case II transport mechanism. The effects of non-ionic surfactants Tween 80 and Span 80 on drug permeation were studied. The non--ionic surfactants in the patches increased the permeation rate, Span 80 exhibiting better enhancement relative to Tween 80. The patches were seemingly free of potentially hazardous skin irritation.

Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation

“…These results were in agreement with those reported previously (21,33 (Fig. 6b), the moisture uptake increased linearly with increasing Methocel ® E15 at 60% RH (R 2 = 0.9454), 75% RH (R 2 =0.9914), and 90% RH (R 2 =0.9904).…”

“…For example, when n=1, the release can be considered Bzero-order^(case II transport), Overall, the formulations containing Eudragit ® RL 100 exhibited GRN release that was higher in rate and extent, compared with those containing Eudragit ® RS 100. Eudragit ® RL 100 contains a higher proportion of the hydrophilic quaternary ammonium groups compared with Eudragit ® RS 100, which may result in a rapid hydration of the matrix and subsequent drug release (33). An increase in the amount and hydrophobicity of the incorporated polymers is known to slow the drug release rates.…”

“…A small amount of moisture in the films is thought to be essential to maintain the stability and integrity of the films and to prevent excessive drying (resulting in brittleness and cracking) of the films (18,39). The water vapor transmission rate (WVTR) is a parameter commonly used to evaluate the amount of moisture transmitted through the transdermal films containing hydrophilic polymers (21,40 (33).…”

Enhanced delivery of diclofenac diethylamine loaded Eudragit RL 100® transdermal system against inflammation

“…The procedure was repeated until films broke in the center. The total number of foldings was called the folding endurance value [24].…”

Fabrication, Development and Characterization of Carvedilol Transdermal Patches: An Empirical Study

“…Folding endurance 11,12 was determined by repeatedly folding one film at the same place till it broke. The number of times the film could be folded at the same place without breaking/ cracking gave the value of folding endurance.…”