Development and in-vitro evaluation of an optimized carvedilol transdermal therapeutic system using experimental design approach

The effect of formulation variables on in-vitro release and permeation properties of carvedilol from transdermal patch was studied by varying one factor at a time as preliminary study. Based on these results, design of experiments technique was applied followed by regression analysis and response surface methodology to optimize formulation variables. Central Composite IV model design was used with four formulation variables: drug loading, matrix thickness, adhesive layer thickness, and propylene glycol concentration. Nineteen formulations were prepared according to the design; and the effect of formulation variables was studied on in-vitro release and permeation profiles of these formulations. In all cases, the permeation profiles paralleled in-vitro release profiles. The drug released at 7 h and 24 h was used as release response parameters while permeation flux obtained was employed as permeation response parameter. All four formulation variables were found to be significant for release properties and three of these exhibited significant effect on permeation profile of carvedilol across artificial membrane. Constrained optimization, using 47.9% of cumulative carvedilol released at 7 h and 99.8% at 24 h as well as 25.7 μg/cm2/h of permeation flux, was applied to obtain desired release and permeation profiles. Experimentally, carvedilol was observed to release from the optimized formulation with 51.4% drug release at 7 h and 98.5% at 24 h with an observed flux value of 27.4 μg/cm2/h across artificial membrane, which showed an excellent agreement with the predicted values. The results of this investigation show that the quadratic mathematical model developed could be used to further predict formulations with desirable release and permeation properties.