Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous...

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Chemical Engineering

Background:

• High-drug loading formulations present manufacturing challenges, including poor flow and tableting difficulties.
• Canagliflozin (CNG) formulations with over 70% drug loading exhibit poor flow and tableting properties.
• Reducing dosage form size through drug loading maximization can decrease manufacturing costs.

Purpose of the Study:

• To address the poor flow and tableting issues of high-drug loading canagliflozin formulations.
• To optimize the moisture-activated dry granulation (MADG) process for canagliflozin.
• To evaluate the impact of granulation fluid level and wet massing time on formulation properties.

Main Methods:

• Moisture-activated dry granulation (MADG), a green granulation process omitting heating and drying steps.
• A 3^2 full-factorial design to optimize granulation fluid level (X1) and wet massing time (X2).
• Granulation of canagliflozin with polyvinylpyrrolidone, followed by tablet compression.

Main Results:

• Regression analysis confirmed significant effects of granulation fluid level and wet massing time on granule and tablet properties (p ≤ 0.05).
• The MADG process significantly improved the flow properties and tableting performance of canagliflozin.
• Optimized conditions (3.41% w/w granulation fluid, 1.0 min wet massing time) yielded good granule flow and acceptable tablets.

Conclusions:

• The MADG process effectively ameliorates poor flow and tableting problems in high-drug loading canagliflozin formulations.
• This green granulation method allows for the use of lower excipient amounts, crucial for uniform dosage unit development.
• MADG offers a viable and cost-effective approach for manufacturing challenging high-drug loading formulations.