Friesen Dwayne T, Shanker Ravi, Crew Marshall, Smithey Daniel T, Curatolo W J, Nightingale J A S
Bend Research Inc., 64550 Research Road, Bend, Oregon 97701, USA.
Mol Pharm. 2008 Nov-Dec;5(6):1003-19. doi: 10.1021/mp8000793.
Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (Tm)/glass-transition temperature (Tg) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.
已使用聚合物羟丙基甲基纤维素乙酸琥珀酸酯（HPMCAS）制备了低溶解度药物的喷雾干燥分散体（SDD）。对于多种药物结构，这些SDD在体外溶出度测定中提供过饱和，并且在体内显著提高生物利用度。在胆盐/卵磷脂体外溶液中，相对于结晶或无定形药物，这些SDD提供无定形药物/聚合物胶体以及游离药物和胶束中药物浓度的增加。作为干粉，SDD是单一的无定形相，其中药物保持无定形且分散，并且在与实际药物产品相关的储存时间内不会结晶。139种配制成SDD的化合物的熔点（Tm）/玻璃化转变温度（Tg）（K/K）与log P图为具有各种物理性质的低溶解度药物提供了合适的制剂策略视角。
