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Drug Delivery and Translational Research

, Volume 8, Issue 3, pp 591–601 | Cite as

Assessment of improved buccal permeation and bioavailability of felodipine microemulsion-based cross-linked polycarbophil gel

  • Mahendra Singh
  • Jovita Kanoujia
  • Poonam Parashar
  • Malti Arya
  • Chandra B. Tripathi
  • V. R. Sinha
  • Shailendra K. Saraf
  • Shubhini A. Saraf
Original Article

Abstract

The oral bioavailability of felodipine (FEL) is very low, i.e., about 15%. This could be due to low water solubility and hepatic first-pass effect. The objective of the present study was to develop FEL microemulsion-based gel, to bypass the first pass effect, for buccal delivery. The optimized FEL microemulsion (OPT-MEF) was used to prepare buccoadhesive gels, with varying concentrations of hydroxypropyl methylcellulose (HPMC) E4M and polycarbophil (PCP), and evaluated. The cross-linking of the PCP gelling agent was done by adjusting the pH with a neutralizing agent, triethanolamine (TEA). The formulations, namely drug suspension, OPT-MEF, microemulsion-based buccal gel containing 1% w/v (MEF-E4M1), 2% w/v (MEF-E4M2), and 3% w/v (MEF-E4M3) of HPMC K4M and 1% w/v (MEF-PCP1), 2% w/v (MEF-PCP2), and 3% w/v (MEF-PCP3) of PCP were prepared and optimized on the basis of ex vivo permeation study, mucoadhesion force, and viscosity. The optimized buccal gel (MEF-PCP1) showed significantly higher (p < 0.01) permeation flux (J = 0.44 ± 0.16 mg/cm2/h), when compared with the drug suspension (J = 0.17 ± 0.14 mg/cm2/h). The permeation enhancement ratio of MEF-PCP1 was found to be 2.59 times higher than that of the aqueous suspension of the drug. The texture profile analysis of MEF-PCP1 was performed which showed spreadability (3.2 mJ), extrudability (151.8 mJ), hardness (13.8 g), and adhesiveness (41.0 g), and results indicated good spreadability and adhesiveness. The rheological study revealed the pseudoplastic flow behavior of MEF-PCP1 buccal gel. The Cmax value 9.21 ± 2.88 μg/ml of MEF-PCP1 gel was found to be significantly higher (P < 0.01) compared to the same dose administered by oral route (Cmax value 3.51 ± 1.74 μg/ml). The relative bioavailability (Fr) of the optimized MEF-PCP1 buccal gel was about 397.39% higher than that of oral route. In conclusion, consistent and effective buccal gel containing optimized FEL-loaded microemulsion, with improved buccal permeation and pharmacokinetic parameters was developed successfully to improve the bioavailability of FEL.

Keywords

Felodipine Buccal gel Buccal delivery Texture analysis Permeation flux 

Notes

Acknowledgements

The authors acknowledge the kind support of IPCA Pharmaceuticals, Pvt. Ltd., Mumbai, for providing the gift sample of felodipine and also acknowledge the UIPS department, Panjab University, Chandigarh, for providing some evaluation facilities for this research work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  • Mahendra Singh
    • 1
  • Jovita Kanoujia
    • 1
  • Poonam Parashar
    • 1
  • Malti Arya
    • 1
  • Chandra B. Tripathi
    • 1
  • V. R. Sinha
    • 2
  • Shailendra K. Saraf
    • 3
  • Shubhini A. Saraf
    • 1
  1. 1.Department of Pharmaceutical SciencesBabasaheb Bhimrao Ambedkar University (A Central University)LucknowIndia
  2. 2.University Institute of Pharmaceutical Sciences, Sector-14Panjab UniversityChandigarhIndia
  3. 3.Department of PharmacyB.B.D.N.I.I.TLucknowIndia

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