Characteristics of multi-component formulation granules formed using distributive mixing elements in twin screw...

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Pharmaceutical powder formulation is critical for drug product performance.
• Twin screw granulation (TSG) is a continuous manufacturing process.
• Distributive mixing elements (DMEs) in TSG influence granule properties.

Purpose of the Study:

• To investigate the impact of pharmaceutical powder formulation characteristics on granule properties.
• To examine the influence of drug loading and active pharmaceutical ingredient (API) type on granules produced by DMEs in TSG.
• To understand the relationship between blend properties and final granule attributes.

Main Methods:

• Utilized high and low drug dose formulations with three different APIs.
• Employed twin screw granulation with distributive mixing elements (DMEs).
• Analyzed dry blend particle size distribution, wet blend dynamic yield strength, granule size distribution, and granule porosity.

Main Results:

• API type and concentration significantly affected dry blend particle size distribution and wet blend dynamic yield strength.
• Granule size distribution was not significantly influenced by API type, but by liquid-to-solid ratio and screw element geometry.
• Granule porosity was dependent on both liquid-to-solid ratio and the dynamic yield strength of the blends.

Conclusions:

• This study is the first to explore the effects of drug loading and API type on granule attributes using DMEs in TSG.
• Formulation composition impacts intermediate blend properties, but final granule size is primarily controlled by process parameters and geometry.
• Understanding these relationships is crucial for optimizing continuous granulation processes and ensuring consistent drug product quality.