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Journal of Pharmaceutical Investigation

, Volume 49, Issue 1, pp 67–85 | Cite as

Canagliflozin loaded SMEDDS: formulation optimization for improved solubility, permeability and pharmacokinetic performance

  • Dilpreet Singh
  • Ashok K. Tiwary
  • Neena BediEmail author
Original Paper
  • 159 Downloads

Abstract

The aim of the present investigation is to systematically optimize and develop microemulsion preconcentrates to improve the solubility and oral bioavailability profile of canagliflozin employing D-optimal mixture design. Preconcentrate constituents, i.e. oils, surfactants and co-surfactants were selected on the basis of solubility studies and their concentration range capable of influencing the formation of microemulsions was determined. D-optimal mixture design was employed for studying the interaction behavior of desired responses and optimized using desirability approach. The optimized formulation was evaluated for its in vitro, ex vivo and in vivo behavior to determine the dissolution rate, permeation rate and oral bioavailability of the drug. The optimized formulation containing Lauroglycol FCC (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) showed desired attributes of measured responses with minimum experimental variation and desirability value of 0.751. The morphological behavior showed uniform nano-structured globules with negligible aggregation as confirmed in transmission electron microscopy. Ex vivo permeation rate of the drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.51, 5.62, 4.52 and 2.98 folds higher, respectively, as compared to drug powder and marketed tablets Compared with the pure drug and commercial tablets, enhanced in vitro dissolution rate of optimized formulation was observed, resulting in 2.56 fold enhancement in Cmax and AUC0–24h following oral administration in fasting wistar rats. Establishment of level A IVIVC for the developed SMEDDS indicated excellent goodness of fit between the in vitro drug release and in vivo drug absorbed. Accelerated stability studies indicated stability of the optimized formulation over 3 months storage.

Keywords

Solubility Canagliflozin Preconcentrates SMEDDS Mixture design 

Notes

Acknowledgements

The authors are highly thankful to Zydus Cadila Limited, Ahmedabad for providing gift sample of canagliflozin. Emerging Life Sciences Facility in Guru Nanak Dev University for carrying out characterization studies is highly acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human and animal rights

All institutional and national guidelines for the care and use of laboratory animals were followed.

Supplementary material

40005_2018_385_MOESM1_ESM.docx (484 kb)
Supplementary material 1 (DOCX 484 KB)

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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesGuru Nanak Dev UniversityAmritsarIndia
  2. 2.Department of Pharmaceutical Sciences and Drug ResearchPunjabi UniversityPatialaIndia

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