Research on Enhancing the Solubility and Bioavailability of Canagliflozin Using Spray Drying Techniques with a...

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Formulation Science

Background:

• Canagliflozin (CFZ) is a BCS class IV drug with poor solubility and bioavailability.
• Enhancing CFZ solubility is crucial for improving its therapeutic efficacy as an SGLT2 inhibitor.

Purpose of the Study:

• To enhance the solubility and oral bioavailability of canagliflozin (CFZ).
• To optimize CFZ-loaded solid dispersions (CFZ-SDs) using a Quality-by-Design (QbD) approach and spray drying technique.

Main Methods:

• A Box-Behnken design (BBD) was employed to optimize CFZ-SD formulation parameters.
• Spray drying was used to create amorphous solid dispersions.
• In vitro and in vivo studies were conducted to evaluate the optimized formulation.

Main Results:

• Optimized CFZ-SDs exhibited significantly improved solubility (9941 μg/mL) and reduced particle size (5.89 μm).
• Spray drying induced amorphization of CFZ, confirmed by SEM, DSC, and PXRD.
• In vitro dissolution rates increased 3.58-fold and 3.84-fold at pH 1.2 and 6.8, respectively, compared to Invokana®.
• In vivo studies showed a 1.9-fold increase in AUC for CFZ-SD compared to CFZ.

Conclusions:

• A QbD-optimized spray-dried solid dispersion formulation effectively enhances CFZ solubility and oral bioavailability.
• This approach offers a promising strategy for improving the delivery of poorly soluble drugs like canagliflozin.