Exploring the Impact of High Shear Mixing Process Parameters on the Physical Characteristics of Excipient Powder Blend by Design of Experiments

Béla Kovács; Erzsébet Orsolya Tőkés; Éva Katalin Kelemen; Katalin Zöldi; Edit Suba; Boglárka Kovács-Deák; István Székely-Szentmiklósi; Francisc Boda; Tibor Casian

doi:10.2478/amma-2024-0016

Béla Kovács 1. Department F1, Biochemistry and Environmental Chemistry, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania 2. Gedeon Richter Romania, 540306 Târgu Mureș, Romania
Erzsébet Orsolya Tőkés 1. Gedeon Richter Romania, 540306 Târgu Mureș, Romania 2. The Doctoral School of Medicine and Pharmacy, Institution Organizing University Doctoral Studies, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
Éva Katalin Kelemen Gedeon Richter Romania, 540306 Târgu Mureș, Romania
Katalin Zöldi Gedeon Richter Romania, 540306 Târgu Mureș, Romania
Edit Suba Gedeon Richter Romania, 540306 Târgu Mureș, Romania
Boglárka Kovács-Deák The Doctoral School of Medicine and Pharmacy, Institution Organizing University Doctoral Studies, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
István Székely-Szentmiklósi 1. Gedeon Richter Romania, 540306 Târgu Mureș, Romania 2. The Doctoral School of Medicine and Pharmacy, Institution Organizing University Doctoral Studies, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
Francisc Boda Department F1, General and Inorganic Chemistry, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
Tibor Casian Department of Pharmaceutical Technology and Biopharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania

DOI: https://doi.org/10.2478/amma-2024-0016

Keywords: placebo, design of experiments, full factorial, manufacturing technology optimization

Abstract

Objective: Dry-route manufacturing technology development poses challenges to formulating scientists, 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 fulfillment 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.