聚合物载体、热熔挤出工艺及下游加工参数对无定形固体分散体吸湿性能的影响。
The effects of polymer carrier, hot melt extrusion process and downstream processing parameters on the moisture sorption properties of amorphous solid dispersions.
作者信息
Feng Xin, Vo Anh, Patil Hemlata, Tiwari Roshan V, Alshetaili Abdullah S, Pimparade Manjeet B, Repka Michael A
机构信息
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA.
Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS, USA.
出版信息
J Pharm Pharmacol. 2016 May;68(5):692-704. doi: 10.1111/jphp.12488. Epub 2015 Nov 21.
OBJECTIVE
The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion and downstream processing parameters on the water uptake properties of amorphous solid dispersions.
METHODS
Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing the hot melt extrusion technology. The sorption-desorption isotherms of solid dispersions and their physical mixtures were measured by the dynamic vapour sorption system, and the effects of polymer hydrophobicity, hygroscopicity, molecular weight and the hot melt extrusion process were investigated. Fourier transform infrared (FTIR) imaging was performed to understand the phase separation driven by the moisture.
KEY FINDINGS
Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity and higher molecular weight could sorb less moisture under the high relative humidity (RH) conditions. The water uptake ability of polymer-drug solid dispersion systems were decreased compared with the physical mixture after hot melt extrusion, which might be due to the decreased surface area and porosity. The FTIR imaging indicated that the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH.
CONCLUSION
Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability.
目的
本研究旨在评估聚合物载体、热熔挤出及下游加工参数对无定形固体分散体吸水性能的影响。
方法
使用三种聚合物和一种模型药物，利用热熔挤出技术制备无定形固体分散体。通过动态蒸汽吸附系统测量固体分散体及其物理混合物的吸附-解吸等温线，并研究聚合物疏水性、吸湿性、分子量及热熔挤出工艺的影响。进行傅里叶变换红外（FTIR）成像以了解水分驱动的相分离。
主要发现
具有较低亲水性、吸湿性和较高分子量的聚合物载体的固体分散体在高相对湿度（RH）条件下可吸收较少水分。热熔挤出后，聚合物-药物固体分散体系统的吸水能力与物理混合物相比有所降低，这可能是由于表面积和孔隙率降低所致。FTIR成像表明，暴露于高RH后，药物在聚合物基质中分子分散的均匀性发生了变化。
结论
了解制剂和加工对固体分散体吸湿性能的影响对于开发具有所需物理和化学稳定性的药品至关重要。
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