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Co-processing of Atorvastatin and Ezetimibe for Enhanced Dissolution Rate: In Vitro and In Vivo Correlation

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Abstract

Development of fixed dose combinations is growing and many of these drug combinations are being legally marketed. However, the development of these requires careful investigation of possible physicochemical changes during co-processing. This requires investigation of the effect of co-processing of drug combination in absence of excipients to maximize the chance of interaction (if any). Accordingly, the aim was to investigate the effect of co-processing of ezetimibe and atorvastatin on drugs dissolution rate. The objective was extended to in vitro in vivo correlation. Drugs were subjected to wet co-processing in presence of ethanol after being mixed at different ratios. The prepared formulations were characterized using FTIR spectroscopy, X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, and in vitro dissolution testing. These investigations proved the possibility of eutectic system formation after drugs co-processing. This was reflected on drugs dissolution rate which was significantly enhanced at dose ratio and 2:1 atorvastatin:ezetimibe molar ratio compared to the corresponding pure drugs. In vivo antihyperlipidemic effects of the co-processed drugs were monitored in albino mice which were subjected to hyperlipidemia induction using poloxamer 407. The results showed significant enhancement in pharmacological activity as revealed from pronounced reduction in cholesterol level in mice administering the co-processed form of both drugs. Besides, histopathological examinations of the liver showed marked decrease in hepatic vacuolation. In conclusion, co-processing of atorvastatin with ezetimibe resulted in beneficial eutexia which hastened the dissolution rate and pharmacological effects of both drugs.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt

    Mona F. Arafa, Rasha A. Alshaikh, Magdy M. Abdelquader & Gamal M. El Maghraby

  2. School of Pharmacy, University College of Cork, Cork, Ireland

    Rasha A. Alshaikh

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  1. Mona F. Arafa
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  2. Rasha A. Alshaikh
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  3. Magdy M. Abdelquader
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  4. Gamal M. El Maghraby
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Correspondence to Mona F. Arafa.

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Arafa, M.F., Alshaikh, R.A., Abdelquader, M.M. et al. Co-processing of Atorvastatin and Ezetimibe for Enhanced Dissolution Rate: In Vitro and In Vivo Correlation. AAPS PharmSciTech 22, 59 (2021). https://doi.org/10.1208/s12249-021-01925-y

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