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. 2022 Mar 21;23(4):96.
doi: 10.1208/s12249-022-02248-2.

A Fundamental Study on Compression Properties and Strain Rate Sensitivity of Spray-Dried Amorphous Solid Dispersions

S Doktorovová  1 , E H Stone  2 , J Henriques  3
Affiliations

A Fundamental Study on Compression Properties and Strain Rate Sensitivity of Spray-Dried Amorphous Solid Dispersions

S Doktorovová et al. AAPS PharmSciTech. .

Abstract

Amorphous solid dispersions (ASDs) are a proven method of improving the solubility and bioavailability of poorly soluble compounds. Immediate release tablets are frequently used as final dosage form for ASDs. Increasing tableting process throughput during clinical development requires using larger, faster tablet presses which subject materials to higher strain rate. Many pharmaceutical materials show strain rate sensitivity, i.e., yield pressure sensitivity to compression speed. Currently, there is only scattered information available in scientific literature on how ASDs behave under different tablet compression speeds. The purpose of this study was to examine spray-dried ASDs' sensitivity to strain rate under compression in a comprehensive study. We also investigated the drivers for such a strain sensitive behavior. A set of sample spray-dried powders, selected for their range of properties, were compressed using a simulated Korsch XL100 profile at 3 and 30 RPM and V-profile at 0.1 and 300 mm/s on a Phoenix compaction simulator. The sample set included samples with varying API content (0-50% w/w), stabilizing polymer (HPMC, HPMC-AS, PVP-VA), particle size, and bulk densities, produced on spray driers from lab to commercial scale. We identified that all ASD samples showed plastic flow and deformation behavior and form robust compacts at slow compression speeds. At high speed, tablet defects occurred. The strain rate sensitivity observed in this study was comparable or slightly superior to that observed for microcrystalline cellulose, known to be a mildly strain rate-sensitive material. We showed that compression speed is a critical process parameter for ASD-containing tablets.

Keywords: Amorphous solid dispersion; Compaction simulation; Compression; Strain rate sensitivity; Tableting.

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References

    1. Roberts RJ, Rowe C. 1986. The effect of the relationship between punch velocity and particle size on the compaction behaviour of materials with varying deformation mechanisms. J Pharm Pharmacol 1986; 38 (8): 567–71. https://doi.org/10.1111/j.2042-7158.1986.tb03082.x .
    1. Leane MM, Pitt K, Reynolds GK, Dawson N, Ziegler I, Szepes A, Crean AM, RDallagnol R, The Manufacturing Classification System (MCS) Working Group. Manufacturing classification system in the real world: factors influencing manufacturing process choices for filed commercial oral solid dosage formulations, case studies from industry and considerations for continuous processing. Pharm Dev Tech 2018; 23 (10): 964–77. https://doi.org/10.1080/10837450.2018.1534863 .
    1. Kalaria DR, Parker K, Reynolds GK, Laru J. An industrial approach towards solid dosage development for first-in- human studies : application of predictive science and lean principles. Drug Discovery Today. 2020;25(3):505–18. https://doi.org/10.1016/j.drudis.2019.12.012 . - DOI - PubMed
    1. Roberts RJ, Rowe C. The compaction of pharmaceutical and other model materials - a pragmatic approach. Chem Eng Sci. 1987;42(4):903–11. - DOI
    1. Paul S, Shao Yu Chang SY, and Changquan Calvin Sun CC. The phenomenon of tablet flashing — its impact on tableting data analysis and a method to eliminate it. Powder Technol 2017; 305: 117–24. https://doi.org/10.1016/j.powtec.2016.09.054 .

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