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Fabrication, optimization, and in vitro/in vivo evaluation of diclofenac epolamine flash tablet

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Abstract

The objective of this work was to design a diclofenac epolamine (DE) flash tablets (FTs) intended to dissolve in the mouth saliva, thereby improving the DE bioavailability and reducing its first-pass liver metabolism. Design-Expert software was used to build a 31.22 full factorial design (12 runs). FTs were fabricated using lyophilization process. The dissolution response was selected to pick the optimized run. The results indicate that the optimized run (R1) showed the fastest drug dissolution (total dissolution in 12 min). The predicted run (Rp) showed a desirability of about 0.93. Differential scanning calorimetry(DSC) analysis results showed a decrease in the drug melting point of the R1 formulation. Fourier–transform infrared spectroscopy (FTIR) showed the compatibility of the drug with other components of formulation, X-ray powder diffraction (XRPD) analysis showed the evolution of the drug physical state from a crystalline to an amorphous form and scanning electron microscopy(SEM) divugled the disappearance of drug crystals in gelatin strands. The results of the pharmacokinetic study performed in 6 human volunteers evidenced an increase in the maximum DE concentration in plasma and, consequently, an increased bioavailability of the FT formulation as compared with a reference formulation(Fr). Concisely, the developed FTs (R1) showed promising results which could be able to enhance oral bioavailability, reduce the therapeutic dose of the drug, and abate of the complications accompanied with conventional dosage forms.

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Funding

This research was self-financed by the authors.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Mohamed Ahmed El-Nabarawi, Ahmed Hassen Elshafeey & Dina Mohamed Mahmoud

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

    Amani M. El Sisi

Authors
  1. Mohamed Ahmed El-Nabarawi
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  2. Ahmed Hassen Elshafeey
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  3. Dina Mohamed Mahmoud
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  4. Amani M. El Sisi
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All authors read and approved the final manuscript.

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Correspondence to Dina Mohamed Mahmoud.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Faculty of Pharmacy, Cairo University, Egypt; ethical code PI:1721) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

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El-Nabarawi, M.A., Elshafeey, A.H., Mahmoud, D.M. et al. Fabrication, optimization, and in vitro/in vivo evaluation of diclofenac epolamine flash tablet. Drug Deliv. and Transl. Res. 10, 1314–1326 (2020). https://doi.org/10.1007/s13346-020-00709-4

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  • DOI: https://doi.org/10.1007/s13346-020-00709-4

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