Development and characterization of allopurinol-loaded transethosomal gel for topical gout management

Gout refers to the painful inflammation of the joints due to deposition of monosodium urate (MSU) cystals. Treatment of gout commonly involve a biopharmaceutical classification system (BCS) class IV drug, allopurinol (ALLP), which is a xanthine oxidase inhibitor with poor solubility and permeability profile. The current study aimed at the development of ALLP-loaded transethosomes (ALLP-TEs) through thin film hydration technique. Design of experiment (DoE) was optimized via Box-Behnken design analysis and the effects of independent variables was examined over the dependent one's. Optimized ALLP-TEs exhibited mean Z-average diameter (hydrodynamic diameter, Z-avg) of 155.4 ± 0.2 nm, polydispersity index (PDI) of 0.28 ± 0.01, zeta potential (ZP) of -27.0 ± 0.2 mV and percentage entrapment efficiency (%EE) of 80.7 ± 2.4%. Absence of any physical or chemical interaction between drug and excipients was confirmed by Fourier transform infrared (FTIR) spectroscopy while X-ray diffraction (XRD) revealed the successful conversion of crystalline drug into amorphous form. Optimized ALLP-TEs were loaded into carbopol 934-based gel. In vitro and ex vivo evaluation demonstrated sustained drug release and 17.3-fold permeation enhancement compared to allopurinol-loaded plain gel (ALLP-PG), respectively. However, in vivo studies demonstrated that ALLP-TEG-treated group healed more quickly than the others presenting a promising and non-invasive transdermal strategy for the effective gout management.