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Spherical Agglomerates of Lactose Reduce Segregation in Powder Blends and Improve Uniformity of Tablet Content at High Drug Loads

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Abstract

We report here on improved uniformity of blends of micronised active pharmaceutical ingredients (APIs) using addition of spherical agglomerates of lactose and enhanced blend flow to improve tablet content uniformity with higher API loads. Micromeritic properties and intra-particle porosity (using nano-computed X-ray tomography) of recently introduced spherical agglomerates of lactose and two standard lactose grades for the direct compression processes were compared. Powder blends of the individual lactose types and different micronised API drug loads were prepared and subjected to specific conditions that can induce API segregation. Tablet content uniformity during direct compression was related to the lactose material attributes. The distinctive micromeritic properties of the lactose types showed that spherical agglomerates of lactose had high intra-particle porosity and increased specific surface area. The stability of binary blends after intense sieving was governed by the intra-particle porosity and surface roughness of the lactose particles, which determined the retention of the model substance. Greater intra-particle porosity, powder specific surface area, and particle size of the spherical agglomerates provided greater adhesion of micronised particles, compared to granulated and spray-dried lactose. Thus the spherical agglomerates provided enhanced final blend flow and uniformity of tablet content at higher drug loads.

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  1. Reprinted from International Journal of Pharmaceutics, 516/1–2, Dejan Lamešić, Odon Planinšek, Zoran Lavrič, Ilija Ilić, Spherical agglomerates of lactose with enhanced mechanical properties, 247–257, 2017, with permission from Elsevier.

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Acknowledgements

The authors would like to thank dr. Ilija German Ilić from the Faculty of Pharmacy, University of Ljubljana, for support for the direct compression experiments.

Funding

The authors acknowledge financial support from the Slovenian Research Agency (research core funding, No. P1-0189).

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia

    Dejan Lamešić, Blaž Grilc, Robert Roškar & Odon Planinšek

  2. Catalent Pharma Solutions, Catalent Germany Schorndorf GmbH, Steinbeisstraße 1-2, 73614, Schorndorf, Germany

    Dejan Lamešić

  3. Centre for X-Ray Analytics, Empa, 8600, Dübendorf, Switzerland

    Selina Kolokytha, Jürgen Hofmann, Andreas Malekos & Rolf Kaufmann

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  1. Dejan Lamešić
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Contributions

Dejan Lamešić: concept, design of the work, acquisition, analysis and interpretation of the data, drafting the manuscript.

Blaž Grilc: design of the work, acquisition, analysis and interpretation of the data, revising the work

Robert Roškar: acquisition, analysis and interpretation of the data, revising the work

Selina Kolokytha: acquisition, analysis and interpretation of the data, revising the work

Jürgen Hofmann: design of the work, acquisition, analysis and interpretation of the data, revising the work

Andreas Malekos: acquisition, analysis and interpretation of the data, revising the work

Rolf Kaufmann: design of the work, revising the work

Odon Planinšek: design of the work, revising the work, final approval for published work

Corresponding author

Correspondence to Dejan Lamešić.

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The authors declare the granted patent for spherical agglomerates of lactose (US 10,568,837 B2).

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Lamešić, D., Grilc, B., Roškar, R. et al. Spherical Agglomerates of Lactose Reduce Segregation in Powder Blends and Improve Uniformity of Tablet Content at High Drug Loads. AAPS PharmSciTech 23, 17 (2022). https://doi.org/10.1208/s12249-021-02150-3

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