Formulation and Evaluation of Novel Colchicine Liposomal Transdermal Gel for Gout
TL;DR
It is suggested that the formulated liposome-based transdermal colchicine formulation has potential as a topical delivery system for gout management and warrants further preclinical and clinical evaluation.
Abstract
Background: Colchicine is an effective first-line therapy for acute gout; however, its oral administration is associated with gastrointestinal intolerance and systemic toxicity, limiting long-term clinical use. The present study aimed to develop and evaluate a liposome-based transdermal colchicine formulation to improve localized drug delivery while minimizing systemic exposure. Methods: Colchicine-loaded liposomes were prepared using ethanol injection and thin-film hydration methods. The optimized liposomal formulation was characterized for vesicle morphology, particle size, zeta potential, entrapment efficiency, drug content, and stability. The optimized formulation was subsequently incorporated into a Carbopol-based transdermal gel and a Methocel-based transdermal patch. Both dosage forms were evaluated for physicochemical properties, in vitro drug release, ex vivo permeation through goat and human cadaver skin, and accelerated stability. Results: The optimized liposomal formulation (DCF1) exhibited spherical vesicles with a particle size of 651.4 nm and a zeta potential of −1.19 mV. It demonstrated the highest entrapment efficiency (81.71%) and drug content (99.65%). The liposomal gel showed acceptable physicochemical characteristics, including a skin-compatible pH (6.2 ± 0.53), viscosity ranging from 27,160 to 29,400 cps, spreadability of 277 g·cm/s, satisfactory extrudability, and drug content of 99.65%. The transdermal patch exhibited uniform thickness (0.143 ± 0.0039 mm), average weight (33.88 ± 0.23 mg), folding endurance (112 ± 0.23), and adequate tensile strength. The liposomal gel achieved 96.39% cumulative drug release within 12 h and followed the Higuchi release model (R² = 0.9178), indicating diffusion-controlled release. Ex vivo permeation studies demonstrated enhanced colchicine permeation across both goat and human cadaver skin, with cumulative permeation reaching 94.94% and 96.39% after 12 h, respectively. Stability studies under accelerated conditions showed satisfactory retention of drug content over the study period. Conclusion: The developed liposomal transdermal colchicine formulation demonstrated favorable physicochemical characteristics, sustained drug release, effective skin permeation, and acceptable stability. These findings suggest that the formulation has potential as a topical delivery system for gout management and warrants further preclinical and clinical evaluation.