Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Leuven, Belgium.
Pharm Res. 2012 Jan;29(1):251-70. doi: 10.1007/s11095-011-0539-x. Epub 2011 Jul 20.
To investigate the influence of solvent properties on the phase behavior and physical stability of spray-dried solid dispersions containing naproxen and PVP K 25 prepared from binary cosolvent systems containing methanol, acetone and dichloromethane.
The viscosity, polymer globular size and evaporation rate of the spray-drying feed solutions were characterized. The solid dispersions were prepared by spray-drying drug-polymer solutions in binary solvent blends containing different proportions of each solvent. The phase behavior was investigated with mDSC, pXRD, FT-IR and TGA. Further, physical stability of solid dispersions was assessed by analyzing after storage at 75% RH.
The solid dispersions prepared from solvent/anti-solvent mixture showed better miscibility and physical stability over those prepared from the mixtures of good solvents. Thus, solid dispersions prepared from dichloromethane-acetone exhibited the best physicochemical attributes followed by those prepared from methanol-acetone. FT-IR analysis revealed differential drug-polymer interaction in solid dispersions prepared from various solvent blends, upon the exposure to elevated humidity.
Spray-drying from a cocktail of good solvent and anti-solvent with narrower volatility difference produces solid dispersions with better miscibility and physical stability resulting from the simultaneous effect on the polymer conformation and better dispersivity of drug.
研究溶剂性质对含萘普生和 PVP K25 的喷雾干燥固体分散体的相行为和物理稳定性的影响，这些固体分散体是由甲醇、丙酮和二氯甲烷组成的二元共溶剂系统中的喷雾干燥进料溶液的粘度、聚合物球粒大小和蒸发速率来表征。将药物-聚合物溶液在含有不同比例各溶剂的二元溶剂混合物中喷雾干燥制备固体分散体。用 mDSC、pXRD、FT-IR 和 TGA 研究相行为。此外，通过分析在 75% RH 下储存后的固体分散体的物理稳定性。
与由良溶剂混合物制备的固体分散体相比，由溶剂/反溶剂混合物制备的固体分散体表现出更好的混溶性和物理稳定性。因此，由二氯甲烷-丙酮制备的固体分散体表现出最好的物理化学性质，其次是由甲醇-丙酮制备的固体分散体。FT-IR 分析表明，在暴露于高湿度时，由各种溶剂混合物制备的固体分散体中药物-聚合物的相互作用不同。
从具有较窄挥发性差异的良溶剂和反溶剂的混合物中喷雾干燥可以产生具有更好混溶性和物理稳定性的固体分散体，这是由于聚合物构象的同时作用和药物更好的分散性所致。
