Tag Archives: canagliflozin

Preparation and evaluation of self-assembling mixed polymeric nanomicelles drug delivery system for canagliflozin

Nizar Awish Jassem

Department of Pharmaceutics, College of Pharmacy, Ashur University, Baghdad, Iraq

DOI: 10.2478/amma-2025-0053

Background and objective: Mixed polymeric nanomicelles are nanoscale structures produced by the self-assembly of two or more amphiphilic polymers in an aqueous solution. These nanomicelles are of great interest in a variety of fields, including medication delivery, due to their capacity to encapsulate both hydrophobic and hydrophilic drugs, as well as their stability and capacity to enhance the solubility and bioavailability of poorly water-soluble medications. Our study focuses on preparing and evaluating mixed polymeric self-nanomicellizing solid dispersions (MP-SNMSD) of Canagliflozin (CFZ), a sodium-glucose co-transporter-2 inhibitor used in managing Type 2 Diabetes Mellitus (T2DM). Its poor aqueous solubility and bioavailability remain significant challenges.
Materials and methods: The solvent evaporation technique was employed to create CFZ-MP-SNMSDs using Soluplus® as a main carrier and Solutol® HS15 or D-α-tocopherol polyethylene glycol succinate (TPGS) as the second carrier.
Results: Ten formulations with high drug loading and stability are prepared. Optimized CFZ-MP-SNMSD formula, consisting of 1:1:4 of CFZ: Solutol® HS15: Soluplus®, exhibited reduced particle size (68.44 nm) and improved dissolution rates under non-sink conditions in phosphate buffer pH 6.8, with a 58% release in 60 minutes compared to 18% for the pure drug. X-ray diffraction revealed a transition of CFZ to an amorphous state in an optimized CFZ-MP-SNMSD formula, enhancing solubility. The MP-SNMSD formulations demonstrated significant enhancements in solubility and dissolution efficiency, which will improve the oral bioavailability of CFZ.
Conclusion: These findings suggest that MP- SNMSD formulations represent a promising approach to overcoming the limitations of CFZ, providing a foundation for more effective oral drug delivery systems of hydrophobic drugs and improving therapeutic outcomes.

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Ex vivo permeability study and in vitro solubility characterization of oral Canagliflozin self-nanomicellizing solid dispersion using Soluplus® as a nanocarrier

Nizar Awish Jassem1, Shaimaa Nazar Abd Alhammid2

1. Department of Pharmaceutics , College of Pharmacy, Al-Ayen Iraqi University, Thi-Qar, Iraq
2. Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq

DOI: 10.2478/amma-2024-0011

Background and objective: Self-nanomicellizing solid dispersion SNMSD is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability.
Materials and Methods: Soluplus® was chosen as a nanocarrier to improve canagliflozin solubility after screening several polymers using a phase solubility study. The solvent evaporation method was selected for preparing the solid dispersion. The optimal formula was characterized through ex vivo permeability and in vitro studies.
Results: The CFZ-SNMSD formula, with a particle size PS of 60.77±1.00 nm and polydispersity index PDI of 0.06±0.02, has a stable distribution upon dilution to 20-fold with water. The apparent solubility of canagliflozin in the optimized CFZ-SNMSD formula was enhanced by 904.40±4 folds due to amorphization and nanomicellization, as demonstrated by transmission electron microscopy. CFZ-SNMSD formula showed a significant enhancement in dissolution rate compared to the physical mixture and pure drugs. The dissolution efficiency parameter confirms these findings (DE30, CFZ-SNMSD = 77.20% compared to DE30, pure drug = 18.28%). Studies show that canagliflozin’s permeability increases exponentially over time due to Soluplus® dispersibility, solubilization, and glycoprotein inhibitory effect, enhancing bioavailability and overcoming GIT membrane barriers.
Conclusions: The study indicates that canagliflozin self-nanomicellizing solid dispersion systems are promising methods for improving the oral bioavailability of canagliflozin medication.

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