Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• The pharmaceutical industry is exploring continuous manufacturing for efficiency and cost reduction.
• Transitioning to continuous processing necessitates a deep understanding of fundamental process principles and Quality by Design (QbD).

Purpose of the Study:

• To investigate the interplay between formulation parameters, process parameters, granule attributes, and tablet properties.
• To evaluate four distinct drug-binder formulations under varying manufacturing conditions.

Main Methods:

• Utilized Design of Experiments (DOE) to systematically study formulation and process variables.
• Examined two binders (polyethylene glycol and Soluplus®) with two model drugs (metoprolol tartrate and caffeine anhydrous) of varying miscibility.
• Assessed granule properties (size, shape, density, flowability) and tablet properties (strength, friability, dissolution).

Main Results:

• Granule properties for miscible systems were sensitive to powder feed rate and granulator fill degree.
• Granule properties for immiscible systems were primarily influenced by binder concentration.
• Tablet tensile strength correlated with granule size for amorphous binders, while granule friability was critical for brittle binders, with exceptions for caffeine's polymorphic transformation.

Conclusions:

• Drug-binder miscibility significantly dictates the influence of process parameters on granule characteristics.
• Formulation behavior during processing is crucial for predicting and controlling granule and tablet quality in continuous manufacturing.
• Knowledge of formulation behavior is essential for optimizing continuous pharmaceutical production.