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Decoding Fine API Agglomeration as a Key Indicator of Powder Flowability and Dissolution: Impact of Particle Engineering

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Abstract

Purpose

Fine API agglomeration and its mitigation via particle engineering, i.e., dry coating, remains underexplored. The purpose was to investigate agglomeration before and after dry coating of fine cohesive APIs and impact on powder processability, i.e., flowability (FFC), bulk density (BD), and dissolution of BCS Class II drugs.

Method

Ibuprofen (three sizes), fenofibrate, and griseofulvin (5–20 µm), before and after dry coating with varying amounts of hydrophobic (R972P) or hydrophilic (A200) nano- silica, were assessed for agglomeration, FFC, BD, surface energy, wettability, and dissolution. The granular Bond number (Bog), a dimensionless parameter, evaluated through material-sparing particle-scale measures and particle-contact models, was used to express relative powder cohesion.

Results

Significant powder processability improvements after dry coating were observed: FFC increased by multiple flow regimes, BD increased by 25–100%, agglomerate ratio (AR) reduction by over an order of magnitude, and greatly enhanced API dissolution rate even with hydrophobic (R972P) silica coating. Scrutiny of particle-contact models revealed non-triviality in estimating API surface roughness, which was managed through the assessment of measured bulk properties. A power-law correlation was identified between AR and Bog and subsequently, between AR and FFC & bulk density; AR below 5 ensured improved processability and dissolution.

Conclusion

Agglomeration, an overlooked material-sparing measure for powder cohesiveness, was a key indicator of powder processability and dissolution. The significant agglomerate reduction was possible via dry coating with either silica type at adequate surface area coverage. Reduced agglomeration after dry coating also countered the adverse impact of increased surface hydrophobicity on dissolution.

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank Hira Khurshid for her assistance in sample preparation and testing from, and Roopal Bhat, Christopher Kossor, and Siddharth Tripathi for their editorial input. The authors have no conflicts of interest or sources of competing interest to declare. Partial support for this work from IFPRI is gratefully acknowledged.

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  1. New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Newark, New Jersey, 07102, USA

    Sangah Kim, Mirna Cheikhali & Rajesh N. Davé

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  1. Sangah Kim
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  2. Mirna Cheikhali
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  3. Rajesh N. Davé
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Correspondence to Rajesh N. Davé.

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Kim, S., Cheikhali, M. & Davé, R.N. Decoding Fine API Agglomeration as a Key Indicator of Powder Flowability and Dissolution: Impact of Particle Engineering. Pharm Res 39, 3079–3098 (2022). https://doi.org/10.1007/s11095-022-03293-z

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  • DOI: https://doi.org/10.1007/s11095-022-03293-z

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