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.