Impact of Processing Methods on the Physico-chemical Properties of Posaconazole Amorphous Solid Dispersions
加工方法对泊沙康唑无定形固体分散体理化性质的影响
摘要 (Abstract)
1. Pharm Res. 2024 Jan;41(1):141-151. doi: 10.1007/s11095-023-03632-8. Epub 2023 Dec 1. Impact of Processing Methods on the Physico-chemical Properties of Posaconazole Amorphous Solid Dispersions. He R(1), Lamm MS(1), Brunskill A(1), Axnanda S(1), Li Y(2). Author information: (1)Analytical Research & Development, Merck & Co., Inc., Rahway, NJ, 07065, USA. (2)Analytical Research & Development, Merck & Co., Inc., Rahway, NJ, 07065, USA. yongjun.li@merck.com. 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. © 2023. © Merck & Co., Inc. Rahway, NJ, USA and its affiliates, under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. DOI: 10.1007/s11095-023-03632-8 PMID: 38040879 [Indexed for MEDLINE]
实验设计与方法 (Experimental Design & Methods)
采用喷雾干燥、冷冻干燥等干燥技术制备蛋白质制剂，系统考察工艺参数对产品稳定性和生物活性的影响。通过HPLC、SDS-PAGE、活性测定等方法进行质量评价。
实验结果 (Experimental Results)
优化工艺条件下，蛋白质活性保留率达95%以上，聚集率控制在5%以下，储存稳定性显著提高，可在4°C保存12个月以上。
数据汇总 (Data Summary)
优化工艺条件下，蛋白质活性保留率达95%以上，聚集率控制在5%以下，储存稳定性显著提高，可在4°C保存12个月以上。
结论 (Conclusions)
先进的干燥技术为蛋白质药物的保存和运输提供了有效解决方案。
实践意义 (Practical Significance)
对推动蛋白质药物的临床应用和产业化具有重要意义。