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Quality by design (QbD) approach to develop fast-dissolving tablets using melt-dispersion paired with surface-adsorption method: formulation and pharmacokinetics of flurbiprofen melt-dispersion granules

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Abstract

Developing amorphous solid dispersions with good flow properties is always challenging for formulation scientists to convert into tablets. Hence, the present study investigates the impact of the combination of melt-dispersion and surface-adsorption methods to prepare melt-dispersion granules with enhanced dissolution rate and flow properties. This study covers the formulation and pharmacokinetic study of fast-dissolving flurbiprofen tablets using PEG 6000 (hydrophilic carrier) and lactose (adsorbent). Response surface methodology (RSM) using the central composite design (CCD) was used to optimize independent variables like carrier concentrations and adsorbent concentrations, and their interactions with the dependent variables (responses), including solubility, angle of repose, Carr’s index, and cumulative % drug release, were investigated. The optimized formulation was selected based on the numerical optimization method and further investigated for FTIR spectroscopy, differential scanning calorimetry, and X-ray diffractometry. Then, the optimized formulation was compressed into tablets and evaluated for both in vitro dissolution and in vivo pharmacokinetics parameters. In vitro dissolution studies revealed that the prepared fast-dissolving tablets released the drug entirely within 15 min (Q15 of F4 tablets: 99.34 ± 1.24%), whereas conventional tablets took around 60 min for complete dissolution. Pharmacokinetic studies in rats revealed that fast-dissolving tablets showed 1.38-fold higher peak-plasma concentration (Cmax) and 1.39-fold higher bioavailability than conventional tablets. Overall, this study revealed the successful fabrication of fast-dissolving tablets via melt-dispersion paired with the surface-adsorption method to enhance the flow properties and the dissolution rate.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors acknowledge Karthikeya Drugs and Pharmaceuticals Private Limited, Kothapet, Hyderabad, for providing all required chemicals. The authors also acknowledge Jeeva Life Sciences, Uppal, Hyderabad, for giving permission and facilities for animal studies.

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Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA

    Sateesh Kumar Vemula & Michael Repka

  2. Department of Pharmaceutics, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India

    Sateesh Kumar Vemula

  3. Department of Pharmaceutics, GITAM School of Pharmacy, GITAM Deemed to Be University, Rudraram, Patancheru, Sangareddy, Hyderabad, Telangana, India

    Bhaskar Daravath

  4. Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, 38677, USA

    Michael Repka

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  1. Sateesh Kumar Vemula
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  3. Michael Repka
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Contributions

All authors contributed to the study’s conception and design. Formulation and evaluation were performed by Sateesh Kumar Vemula and Bhaskar Daravath. Sateesh Kumar Vemula wrote the first draft of the manuscript, and the final corrections were made under the supervision of Michael Repka. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Sateesh Kumar Vemula or Michael Repka.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The in vivo bioavailability studies are approved by the institutional animal ethical committee (IAEC Approval No: CPCSEA/IAEC/JLS/006/02/17/006). All institutional and national guidelines for the care and use of laboratory animals were followed.

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The authors declare no competing interests.

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Vemula, S.K., Daravath, B. & Repka, M. Quality by design (QbD) approach to develop fast-dissolving tablets using melt-dispersion paired with surface-adsorption method: formulation and pharmacokinetics of flurbiprofen melt-dispersion granules. Drug Deliv. and Transl. Res. 13, 3204–3222 (2023). https://doi.org/10.1007/s13346-023-01382-z

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