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Preparation and Transformation of Solid Glass Solutions of Clotrimazole to Nanosuspensions with Improved Physicochemical and Antifungal Properties

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Abstract

Purpose

Evaluating the feasibility of two-step preparation of clotrimazole solid glass solutions for improving its physicochemical properties, intrinsic dissolution, and antifungal activity.

Methods

Co-grinding with selected coformers including vitamin C and L-arginine was employed to form co-amorphous dispersions; then, a polymeric carrier was added to form a homogenous glass solution. The solid solutions were converted to nanosuspensions after reconstitution and ultrasonication. The dispersions were characterized for equilibrium solubility, intrinsic dissolution, particle size, and zeta potential. Solid state characterization was carried out using differential scanning calorimetry, X-ray powder diffraction, and Infrared spectroscopy. The antifungal activity was evaluated using candida albicans species.

Results

Equilibrium solubility indicated superb increase in clotrimazole solubility (more than 289 times) from glass solutions compared to pure crystalline drug. The intrinsic dissolution data showed 64% ± 0.34 of drug released within 15 min, and complete dissolution was obtained in 45 min. The ideal formula showed nanosized particles after dispersion in water (225 nm), optimum zeta potential (20.20 µV), and polydispersity index (0.35). Solid state characterization showed shortened peaks and diffraction lines of the glass solutions compared to parent components. The biological activity of the reconstituted nanosuspension showed decreased minimum inhibitory concentration by 50% and increased area of growth inhibition zones of candida albicans by more than 28% compared to drug solution.

Conclusions

These findings suggest that solid glass solutions and its derived nanosuspensions of clotrimazole with ascorbic acid and polyvinyl pyrrolidone could be a valuable solution for maximizing drug bioavailability.

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Acknowledgements

The authors of this research would like to acknowledge the financial support offered by Taif University Researchers Supporting Project number (TURSP-2020/50), Taif University, Taif, Saudi Arabia. The authors would also like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant: 19-MED-1-01-0024 to Mohammed A.S. Abourehab.

Funding

The authors of this research received financial support offered by Taif University Researchers Supporting Project number (TURSP-2020/50), Taif University, Taif, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P. O. Box 11099, Taif, 21944, Saudi Arabia

    Ahmed M. Abdelhaleem Ali & Musarrat Husain Warsi

  2. Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    Mohammed A. S. Abourehab

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt

    Mohammed A. S. Abourehab

  4. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt

    Adel Ahmed Ali

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  1. Ahmed M. Abdelhaleem Ali
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  2. Musarrat Husain Warsi
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  3. Mohammed A. S. Abourehab
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  4. Adel Ahmed Ali
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Correspondence to Ahmed M. Abdelhaleem Ali.

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Ali, A.M.A., Warsi, M.H., Abourehab, M.A.S. et al. Preparation and Transformation of Solid Glass Solutions of Clotrimazole to Nanosuspensions with Improved Physicochemical and Antifungal Properties. J Pharm Innov 17, 1420–1433 (2022). https://doi.org/10.1007/s12247-021-09595-w

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