Microdynamic flowability for early API characterisation: A case study on Palbociclib

Abstract

This study explores microdynamic flowability as an innovative approach for early active pharmaceutical ingredient (API) characterisation, when compounds are often scarce and/or expensive. By incorporating small-scale flow measurements during the pre-formulation stage, we aim to support strategic decision-making in formulation development and process design.

Highlights

• Powder flow measurements are integrated into the earliest stages of drug development.
• Pre-formulation flow data relevant to R&D tablet presses can now be generated.
• Micronisation enhances dissolution but worsens flowability due to agglomeration.
• Advanced image analysis enables quantitative detection of powder agglomeration.
• Microdynamic flow studies aid early formulation development and process design.

Laboratory-scale micronisation of the poorly water-soluble drug Palbociclib, while enhancing dissolution, was found to adversely affect flowability. Agglomeration driven by cohesive forces was quantitatively described for the first time via image analysis using sample quantities of less than 200 mg. Our findings demonstrate that microdynamic flow studies provide critical insights into the processability of APIs under low-stress conditions, such as those relevant to research and development (R&D) tablet presses.

These results highlight the value of advanced flowability analysis in early-stage development, enabling improved understanding and control of powder processing in pharmaceutical manufacturing and particle engineering.

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Materials

Traditional mechanical milling was applied to a BCS Class II (poor water-soluble) drug candidate, Palbociclib (MSN Pharmaceuticals Inc., New Jersey, USA), which requires to be processed to enhance dissolution and bioavailability. As a cornerstone therapy for advanced or metastatic breast cancer, its high cost and limited availability during early-stage development further highlight the importance of emerging powder flow analytical techniques that minimise sample consumption. Untreated API was used as reference to evaluate the effect of milling on flow and dissolution properties.

Standard microcrystalline cellulose (MCC) grades, including Vivapur® 101 (Ph. Eur grade, JRS Pharma, Rosenberg, Germany), Avicel® PH-102 (Ph. Eur grade, FMC BioPolymer, Ireland), and Avicel® PH-200 (Ph. Eur grade, JRS Pharma, Rosenberg, Germany), were employed as reference materials to rank the API’s flow behaviour. These MCC grades span a spectrum of flow properties typically encountered in die-filling processes during pharmaceutical manufacturing. Their inclusion provided a comprehensive framework for benchmarking and validation, since traditional bulk flow measuring techniques could not be applied in this study.

David Blanco, Nicolas Pätzmann, Pablo García-Triñanes, Microdynamic flowability for early API characterisation: A case study on Palbociclib, Pharmaceutical Science Advances, Volume 3, 2025, 100069, ISSN 2773-2169, https://doi.org/10.1016/j.pscia.2025.100069.

Read also our introduction article on Microcrystalline Cellulose here: