Exploring the impact of high shear mixing process parameters on the physical characteristics of excipient powder blend by design of experiments

Abstract

Objective: Dry-route manufacturing technology development poses challenges to pharmaceutical technology research specialists, relying on active substance characteristics, excipient selection, and parameter optimization. Amongst various technological possibilities high shear mixing generally ensures dosage uniformity and tablet dissolution through influential shear forces, potentially enhancing dry powder blend processability. This study explores the processability of a placebo formulation within the quality by design framework to address some of the aforementioned challenges. Methods: A 24 full-factorial experimental design was used to assess the manufacturability of a placebo formulation via high shear mixing. The effect of impeller and chopper speed, high shear mixing time, and homogenization/lubrication times on powder blend rheology and compression properties was investigated. Results: The findings of the present study showed that product critical quality attributes like resistance to crushing or disintegration time are mainly dependent on the mixing efficiency translated by the impeller speed and high shear mixing time. Software augmented process development enabled the attainment of the design space, ensuring the fulfilment of desired product performance criteria. Furthermore, the study has also shown that the careful selection of excipients is crucial in the case of dry-route manufacturing technologies, as sodium lauryl sulphate can noticeably influence the processability of powder blends due to its lubricant properties. Conclusions: Considering the advantages and challenges raised by high-shear mixing, software aided data analysis can further augment the formulation, scale-up and lifecycle management of products developed using this technological process.