Development and Optimization of Matrix-Type Transdermal Patches of Allopurinol for Enhanced Therapeutic Efficacy

Abstract

Oral allopurinol is widely used to reduce uric acid formation, but development of an alternative sustained-delivery system may help maintain drug release while reducing the need for frequent administration. This study developed matrix-type allopurinol transdermal patches using ethylcellulose (EC) and polyvinylpyrrolidone K-30 (PVP K-30) and evaluated the influence of polymer composition and selected chemical permeation enhancers on in vitro drug release. Patches containing 20% w/w allopurinol were prepared by solvent evaporation. EC and PVP K-30 were used as matrix-forming polymers, while dibutyl phthalate at 30% w/w of the total polymer weight served as a plasticizer. Five polymer ratios were screened without an enhancer. The selected EC:PVP ratio of 3:2 was subsequently formulated with dimethyl sulfoxide (DMSO), Tween 80, eucalyptus oil, or olive oil at 2%, 5%, and 10% w/w. The patches were evaluated for appearance, thickness, weight variation, drug content, flatness, tensile strength, surface pH, moisture-related properties, and in vitro drug release. Release studies were performed for 24 h using a USP apparatus II modified paddle-over-disc method at 32 +/- 0.5°C in 20% methanol-phosphate-buffered saline, pH 7.4. The patches were clear, smooth, flexible, uniform, and free of visible air bubbles. Thickness, weight, drug content, tensile strength, and surface pH ranged from 0.246 to 0.276 mm, 164.37 to 172.01 mg, 94.12% to 98.23%, 0.346 to 0.438 kg/mm², and 5.7 to 6.6, respectively. All formulations demonstrated 100% flatness. Among enhancer-free patches, the EC:PVP 3:2 formulation produced the greatest 24-h cumulative release, 59.66 +/- 0.81%. The incorporation of enhancers increased release to different extents. Tween 80 at 2% produced the highest 24-h cumulative release, 88.72 +/- 2.59%, followed by eucalyptus oil at 10%, 83.52 +/- 3.11%, and DMSO at 10%, 78.29 +/- 3.66%. An EC:PVP K-30 ratio of 3:2 provided the most favorable release among the polymer combinations examined. Tween 80 at 2% generated the highest in vitro release and was identified as the lead formulation under the conditions studied.