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2000
Volume 15, Issue 5
  • ISSN: 2468-1873
  • E-ISSN: 2468-1881

Abstract

Aim

The study aimed to develop and optimize itraconazole nanocrystal-loaded hydrogel 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.

Methods

Nanocrystals were prepared using the solvent anti-solvent precipitation method followed by ultrasonication. The solvent-antisolvent and stabilizer were selected based on a screening 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% ). The gels that were developed underwent assessment for their physical appearance, pH determination, rheological study, spread ability study, drug release study, and permeation study.

Results

The optimized nanocrystal formulation (D14) presented that the observed values of drug release in 10 min 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 approximately a 37.76-fold increase in saturation solubility compared to the saturation solubility of the pure drug. Among the developed nanocrystal-loaded gel formulations, the D15 formulation (containing 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 characteristics. The 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 itraconazole nanocrystal-loaded hydrogel for topical delivery with improved drug release and permeation characteristics. The release kinetics of the drug best fitted the Higuchi model (2 =0.9837), suggesting the sustained release of the drug from the gel matrix.

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2024-08-20
2025-10-11

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In-vitro and Ex-vivo Evaluation of Central Composite Design Implemented Formulation and Characterization of Itraconazole Nanocrystal Loaded Hydrogel
Curr Nanomed 15, 646 (2025); https://doi.org/10.2174/0124681873324231240815093901
/content/journals/cnanom/10.2174/0124681873324231240815093901
/content/journals/cnanom/10.2174/0124681873324231240815093901
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  • Article Type:     Research Article
Keyword(s): antifungal activity; Central composite design; hydrogel; nanocrystal; saturation solubility; solvent-antisolvent precipitation method; stabilizers

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