Release of Ropinirole in Acrylate Transdermal Patches: Mutual Interactions Between Formulation Variables

Abstract

The aim of this study is to evaluate the cooperative interactions between formulation variables of ropinirole transdermal patches and characterize the effects of drug loading and crystallinity, degree of ionization and drug-polymer solubilization, functionalization of acrylate polymeric basis, and the addition of permeation enhancers over the release profiles. Several series of transdermal films based on carboxylic or hydroxylic acrylates (DuroTak®) and containing 1 to 10% ropinirole hydrochloride were laminated by mold-casting and evaporation. Formulations were characterized for crystallinity, drug particle size, drug assay, and residual solvents. Release profiles were obtained at different drug ionization state using paddle over disk apparatus. Mechanisms were elucidated with nonlinear data fitting of relevant release equations. Fickian and erosion processes were evaluated with the Peppas-Sahlin equation, and burst release risks were estimated as an independent term added to Higuchi kinetics. X-ray diffraction and microscopy evidenced differences in drug-polymer solubilization and density of drug crystals. Concerning drug release, area under the curve of dissolved quantities and release percentage were discriminant variables in mutual influence. Peppas-Shalin equation was the majority descriptor of release suggesting a combination of Fickian and erosion processes, revealing a decrease in the Fickian component as drug loading increased. Major burst release risks were evidenced mostly with Higuchi kinetics with vinylacetate acrylates. The carboxylic polymer without vinylacetate provided the best release extent, being more highly efficient as lower the drug loading was. Permeation enhancers with carboxylic or aliphatic radicals have, additionally, modified the release properties of ropinirole. Chemical interactions between the drug and acrylic polymers have been demonstrated. Only the effect with carboxylic polymer is pH dependent. The vinyl acetate comonomer reduces the drug release rate most effectively in formulations with low drug loads. The acrylic polymers without vinylacetate achieved the highest drug solubilization and thus the highest degree of release, providing a release of approximately 15% of the drug load.

Keywords: Acrylate-vinylacetate copolymer; Drug loading; Release; Ropinirole; Transdermal.