A mixture experiment approach for controlling the dissolution rate of a sustained-release tablet

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Sustained-release tablet formulations exhibited instability due to lactose interactions.
• Acceptable pharmacokinetic properties necessitated the development of stable alternatives.

Purpose of the Study:

• To develop stable sustained-release formulations that replicate the in vitro drug release of unstable formulations.
• To identify optimal formulation compositions using a statistically designed experiment.

Main Methods:

• Utilized a statistically designed mixture experiment to generate and test alternative tablet formulations.
• Employed dissolution testing to evaluate drug release characteristics.
• Developed a statistical regression model based on the Higuchi equation to predict dissolution profiles.

Main Results:

• Identified specific ratios of Methocel K4MCR Premium and Methocel K100MCR Premium for stable formulations.
• Demonstrated that replacing lactose with calcium phosphate dibasic anhydrous resolves formulation instability.
• Successfully generated dissolution profiles matching the original unstable formulations.

Conclusions:

• Stable sustained-release tablet formulations can be achieved by careful selection of excipients and their ratios.
• Calcium phosphate dibasic anhydrous is a suitable alternative to lactose for preventing instability in these formulations.
• Statistical modeling effectively guides the development of pharmaceutical formulations with desired drug release characteristics.