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Impact of Processing Methods on the Physico-chemical Properties of Posaconazole Amorphous Solid Dispersions

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Abstract

Background & Purpose

Different methods have been exploited to generate amorphous solid dispersions (ASDs) of poorly water-soluble drugs. However, the impact of processing methods on drug stability and dissolution hasn’t been studied extensively. The purpose of the current study is to investigate the impact of the two common ASD processing methods, hot-melt extrusion (HME) and spray drying, on the chemical/physical stability and supersaturation of Posaconazole (Posa) based ASDs.

Methods & Results

ASDs with 25% drug loading in hydroxypropylmethylcellulose acetate succinate were prepared using HME, and two types of spray dryers, a Procept Sprayer (ASD-Procept) and a Nano Sprayer (ASD-Nano). The relative physical stability of these ASDs upon exposure to heat and crystalline API seeding followed the order: ASD-Nano > ASD-Procept ≈HME. ASD-Procept and ASD-Nano showed similar chemical stability, slightly less stable than HME under 40°C/75%RH. All three ASDs demonstrated similar supersaturation induction times, and de-supersaturation kinetics with or without crystalline seeds.

Conclusions

Posa ASDs prepared via spray drying were chemically less stable compared with HME, which can be attributed to their smaller particle size and hollow structure allowing oxygen penetration. For ASD-Procept and HME, the detailed phase changes involving recrystallization of amorphous Posa and a solid-solid phase transition from Posa Form I to Form Ia during the seed-induced studies were proposed. Similar dissolution and supersaturation-precipitation kinetics of three Posa ASDs indicated that any residual nanocrystals in the bulk ASDs were not enough to induce crystallization to differentiate ASDs made by three processing methods.

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Acknowledgements

We would like to acknowledge Dr. Justin Newman for assisting with variable temperature XRD experiments.

Funding

All work described here was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

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Authors and Affiliations

  1. Analytical Research & Development, Merck & Co., Inc., Rahway, NJ, 07065, USA

    Ru He, Matthew S. Lamm, Andrew Brunskill, Stephanus Axnanda & Yongjun Li

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  1. Ru He
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Correspondence to Yongjun Li.

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The authors (employment by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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He, R., Lamm, M.S., Brunskill, A. et al. Impact of Processing Methods on the Physico-chemical Properties of Posaconazole Amorphous Solid Dispersions. Pharm Res 41, 141–151 (2024). https://doi.org/10.1007/s11095-023-03632-8

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