Influence of Drying Methods on Redispersibility and Dissolution of Canagliflozin Nanocrystals: A Comparative Approach

TL;DR

This study compares drying methods to improve the solubility and performance of canagliflozin nanocrystals for better drug delivery.

Contribution

The study introduces a comparative analysis of fluid bed granulation and spray-drying for stabilizing canagliflozin nanocrystals.

Findings

Spray-drying achieved the highest redispersibility index of 94% for canagliflozin nanocrystals.

Spray-dried nanocrystal tablets showed a three-fold increase in drug release compared to the marketed product.

The tablets demonstrated improved dissolution under simulated gastrointestinal pH conditions.

Abstract

Background/Objectives: Canagliflozin (CFZ) is the first sodium glucose co-transporter 2 (SGLT-2) inhibitor and is characterized by poor water solubility and permeability, resulting in low oral bioavailability. In this study, a CFZ nanosuspension (CFZ-NS) was converted into a solid form to improve the physical stability of CFZ nanocrystals (CFZ-NCs) and to enable formulation as a tablet dosage form. Methods: To achieve adequate redispersibility of dried CFZ-NCs, fluid bed granulation and spray-drying methods were employed, and the effects of critical process parameters were investigated. The stability of spray-dried nanocrystal tablets (NCs-SD-TAB) was evaluated over a three-month period under storage conditions of 25 ± 2 °C with 60 ± 5% relative humidity (RH) and 40 ± 2 °C with 75 ± 5% RH. Results: The highest redispersibility index (94%) was obtained using the spray-drying method. Tablets prepared with spray-dried NCs-SD-TAB exhibited a significantly higher in vitro dissolution rate under non-sink conditions compared with control tablets prepared using unprocessed CFZ with the same excipients, as well as the marketed product. NCs-SD-TAB showed an approximately three-fold increase in drug release at 15 min in 0.1 N HCl, with a pH 4.5 acetate buffer and pH 6.8 phosphate buffer, which simulate gastrointestinal pH conditions, relative to the marketed product. Conclusions: Overall, these results indicate that nanocrystal technology represents a promising approach for CFZ as an improved oral drug-delivery system, primarily due to its solubility enhancement capabilities.

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