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Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm

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Abstract

Aim

Canagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ.

Methods

Solid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent. The formed solid SMEDDS were characterized for physicochemical and solid state attributes. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to confirm the spherical morphology. In vitro dissolution, ex vivo permeability and in vivo pharmacokinetic studies were conducted to determine the release rate, permeation rate and absorption profile of CFZ, respectively. Pharmacodynamic studies were done as per standard protocols.

Results

The optimized solid SMEDDS exhibited acceptable practical yield and flow properties and is vouched with enhanced amorphization, nanoparticulate distribution and acceptable drug content. The spherical morphology of solid SMEDDS and reconstituted SMEDDS were confirmed in SEM and TEM, respectively. In vitro dissolution studies revealed multi-fold release behavior in CFZ in various dissolution media, whereas, remarkable permeability was observed in jejunum segment of rat intestine. Pharmacokinetic studies of CFZ in solid SMEDDS demonstrated 2.53 and 1.43 fold enhancement in Cmax and 2.73 and 1.98 fold in AUC 0-24h, as compared to pure API and marketed formulation, respectively. Pharmacological evaluation of solid SMEDDS revealed enhanced anti-diabetic activity of CFZ through predominant SGLT II inhibition in rats, as evident from evaluation of biochemical levels, urinary glucose excretion studies and SGLT II expression analysis.

Conclusion

The current work describes significant improvement biopharmaceutical properties of CFZ in solid SMEDD formulation.

Graphical Abstract: Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm

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Acknowledgements

The authors are highly grateful to Zydus Cadila Limited, India for providing ex gratia of CFZ for our research work. The authors acknowledge University Grants Commission (UGC), Delhi for University with Potential for Excellence (UPE) and Department of Science and Technology (DST), Government of India PURSE, CPEPA and FIST schemes for strengthening infrastructure of Guru Nanak Dev University, Amritsar. The authors are highly thankful to Alomone Labs, Israel for providing ex gratia sample of SGLT II primary antibody for our research work. Cooperation of Mr. Brahmjot Singh from Department of Pharmaceutical Sciences for helping in animal studies is deeply acknowledged.

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Correspondence to Neena Bedi.

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Singh, D., Singh, A.P., Singh, D. et al. Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm. DARU J Pharm Sci (2020). https://doi.org/10.1007/s40199-020-00330-3

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