The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions
The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions
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DOI：
10.3390/pharmaceutics12030212
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发表时间：
2020-03-01
期刊：
影响因子：
5.4
通讯作者：
Higginbotham, Clement L.
中科院分区：
文献类型：
--
作者：
Hurley, Dean;Davis, Mark;Higginbotham, Clement L.
冷却对多组分热熔挤压固体分散体[SD]的结晶度、固相和溶解性能的影响对于成功制备非晶态十二烷基硫酸钠非常重要，这是一个未见报道的领域，特别是在提高这些特定体系的稳定性的背景下。考察了其热固态性质、结晶度、药物-聚合物相互作用、溶解度和物理稳定性随时间的变化。X-射线粉末衍射仪[XRPD]和超差示扫描量热法[DSC]证实吲哚美辛[INM]已转变为非晶态，但泊洛沙姆407[P407]的加入对SD制剂的结晶度和溶解度有显著影响。光谱分析表明，在pH 1.2条件下，INM的溶出速率高于无定形和纯INM，3h和24 h的动力学溶解度分别为20.63mU g/mL和34.7mU g/mL。XRPD证实，INM在聚乙烯吡咯烷酮-乙酸乙烯酯共聚物[PVP VA64]和塑料S-630[PL-S630]的固溶体中5个月的稳定性测试后仍为无定形。尽管冷却对INM的结晶度和溶解度有显著影响，但所采用的冷却方法对INM随时间的无定形稳定性没有任何显著影响。
The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. The thermal solid-state properties, degree of crystallinity, drug-polymer interactions, solubility and physical stability over time were investigated. X-ray powder diffraction [XRPD] and hyper differential scanning calorimetry [DSC] confirmed that indomethacin [INM] was converted to the amorphous state; however, the addition of poloxamer 407 [P407] had a significant effect on the degree of crystallinity and the solubility of the SD formulations. Spectroscopy studies identified the mechanism of interaction and solubility studies, showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 mu g/mL and 34.7 mu g/mL after 3 and 24 h. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone S-630 [PL-S630]. Although cooling had a significant effect on the degree of crystallinity and on solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time.