In-vitro and Ex-vivo Evaluation of Central Composite Design Implemented Formulation and Characterization of Itraconazole Nanocrystal Loaded Hydrogel
Aim:
The study aimed to develop and optimize itraconazole nanocrystal-loaded hydro-gel by central composite design.
Background:
Itraconazole is a broad spectrum antifungal drug classified as a BCS Class II drug with poor water solubility that limits its dermal availability and serves as a rate-limiting barrier in topical formulations. Thus, it was aimed at developing and optimizing itraconazole nanocrystal-loaded hydrogel to improve its skin penetration by solving its solubility issue.
objective:
The objective of the study was to improve the topical delivery of itraconzole by solving its solubility issue.
Methods:
Nanocrystals were prepared using the solvent anti-solvent precipitation method fol-lowed by ultrasonication. The solvent-antisolvent and stabilizer were selected based on a screen-ing study. Optimizations of nanocrystal formulation were carried out using Central Composite Design (CCD). The Optimized formulation(D14) was characterized for % drug release, saturation solubility, particle size, zeta potential, PDI, and DSC analysis.The optimized formulation D14 was incorporated into hydrogel using HPMC K15M at three different concentrations (1%, 1.5%, and 2% w/w). The gels that were developed underwent assessment for their physical appearance, pH determination, rheological study, spread ability study, drug release study, and ex-vivo permea-tion study.
Results:
The optimized nanocrystal formulation (D14) presented that the observed values of Drug Release in 10min % was 93.532 ± 0.263 and Saturation solubility of 624.12 ± 0.76 μg/ml. The mean particle size of the optimized nanocrystal formulation was 253.7nm, with a PDI value of 0.202 and zeta potential of 26.4 mv ± 0.7mv possesses good physical stability. There is approxi-mately a 37.76-fold increase in saturation solubility compared to the saturation solubility of the pure drug, among the developed nanocrystal-loaded gel formulation. The D15 formulation (con-taining 1% HPMC) demonstrated maximum drug release up to 87.948 ± 0.298% within 24 hours compared to the control gel that showed 19.792 ± 0.046% and desirable rheological characteris-tics. The ex-vivo permeation study of D15 gel revealed 4.6 times enhanced permeation compared to the control gel
Conclusion:
In conclusion, the present study successfully demonstrated the formulation of itra-conazole nanocrystal-loaded hydrogel for topical delivery with improved drug release and perme-ation characteristics. The release kinetics of the drug best fitted the Higuchi model (r2 =0.9837), suggesting the sustained release of the drug from the gel matrix.
