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Stimulatory Effects of Soluplus® on Flufenamic Acid β-Cyclodextrin Supramolecular Complex: Physicochemical Characterization and Pre-clinical Anti-inflammatory Assessment

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Abstract

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/β-cyclodextrin (β-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with β-CD alone and β-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:β-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.

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Funding

Authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research via research group number RG-1441-460.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, Saudi Arabia

    Sultan Alshehri, Syed Sarim Imam, Mohammad A. Altamimi, Afzal Hussain & Faiyaz Shakeel

  2. College of Pharmacy, Al Marefa University, Riyadh, Saudi Arabia

    Sultan Alshehri

  3. Pharmacy, Ministry of Defense, King Abdulaziz Air Base Hospital, Dhahran, Saudi Arabia

    Abdulhakeem Alshehri

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  1. Sultan Alshehri
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Correspondence to Sultan Alshehri.

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The protocol for these studies was reviewed and approved by the “Animal Ethics Committee of King Saud University, Riyadh, Saudi Arabia (approval number KSU-SE-19-19).”

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Supplementary Figure S1a-b: Nuclear magnetic resonance spectra (1H) of β-CD and Soluplus. Supplementary Figure S2a-b: Nuclear magnetic resonance spectra (13C) of β-CD and Soluplus. (DOCX 105 kb)

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Alshehri, S., Imam, S.S., Altamimi, M.A. et al. Stimulatory Effects of Soluplus® on Flufenamic Acid β-Cyclodextrin Supramolecular Complex: Physicochemical Characterization and Pre-clinical Anti-inflammatory Assessment. AAPS PharmSciTech 21, 145 (2020). https://doi.org/10.1208/s12249-020-01684-2

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