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Egg White Protein Carrier-Assisted Development of Solid Dispersion for Improved Aqueous Solubility and Permeability of Poorly Water Soluble Hydrochlorothiazide

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Abstract

Hydrochlorothiazide (HTZ) is a first-line drug used in the treatment of hypertension suffered from low oral bioavailability due to poor aqueous solubility and permeability. Hence, lyophilized egg white protein-based solid dispersion (HTZ-EWP SD) was developed to explore its feasibility as a solid dispersion carrier for enhanced aqueous solubility and permeability of HTZ. The HTZ-EWP SD was prepared using the kneading method. HTZ-EWP SD was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectroscopy (FT-IR), powder X-ray diffractometer (PXRD), solubility, in vitro dissolution, and ex vivo permeation studies. The physico-chemical evaluation suggested the formation of the solid dispersion. Optimized HTZ-EWP SD4 drastically enhanced (~32-fold) aqueous solubility (~16.12 ± 0.08 mg/mL) over to pure HTZ (~ 0.51 ± 0.03 mg/mL). The dissolution study in phosphate buffer media (pH 6.8) revealed that HTZ-EWP SD4 significantly enhanced the release rate of HTZ (~ 87 %) over to HTZ (~ 25 %). The permeation rate of HTZ from optimized HTZ-EWP SD4 was enhanced significantly (~ 84 %) compared to pure HTZ (~ 24 %). Optimized HTZ-EWP-SD4 enhanced the rate of HTZ dissolution (~ 86 %) in FeSSIF (fed state simulated intestinal fluid), compared to a low dissolution rate (~ 72 %) in FaSSIF (fasted state simulated intestinal fluid) state after 2-h study. Obtained results conclude that lyophilized egg white protein can be utilized as an alternative solid dispersion carrier for enhancing the solubility and permeability of HTZ.

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Acknowledgements

The corresponding author would like to thank Dr. Shirish P. Jain, Principal, Rajarshi Shahu College of Pharmacy, Buldhana, for the technical support to submit this manuscript.

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  1. Rajarshi Shahu College of Pharmacy, Malvihir, Botha Road, Buldhana, Maharashtra, India

    Darshan R. Telange & Shirish P. Jain

  2. School of Pharmacy & Technology Management, NMIMS (Deemed to be University), Hyderabad Campus, Hyderabad, Telangana, India

    Anil M. Pethe

  3. Institute of Chemical Technology, Mumbai, Maharashtra, India

    Prashant S. Kharkar

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Telange, D.R., Jain, S.P., Pethe, A.M. et al. Egg White Protein Carrier-Assisted Development of Solid Dispersion for Improved Aqueous Solubility and Permeability of Poorly Water Soluble Hydrochlorothiazide. AAPS PharmSciTech 22, 94 (2021). https://doi.org/10.1208/s12249-021-01967-2

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