Worku Zelalem Ayenew, Aarts Jolie, Van den Mooter Guy
Drug Delivery and Disposition, KU Leuven , Herestraat 49, 3000 Leuven, Belgium.
Mol Pharm. 2014 Apr 7;11(4):1102-8. doi: 10.1021/mp5001313. Epub 2014 Feb 26.
Solid dispersions are preferentially formulated as solid dosage forms such as tablets and capsules. The structural stability of the solid dispersions has not been adequately explored during post spray drying manufacturing processes. In this paper, we describe the influence of compression forces on solid dispersions made up of naproxen and PVP-VA 64 prepared by spray drying. Compression of the solid dispersion containing 30% (w/w) of naproxen led to low intensity of the powder X-ray diffraction (PXRD) halo pattern maxima at 2θ = 16.11°, and the uncompressed samples also exhibit higher glass transition broadening than the compressed samples after 21 days storage at 75% RH at ambient temperature which indicates structural changes in the solid dispersion. The intensity of the vibration band at 1654 cm(-1) originating from the interaction between the hydrogen of the carboxylic acid moiety of NAP and the amide carbonyl moiety of PVP-VA 64 was increased for the compressed samples. The consequence of compression was further amplified after a long-term stability study (5 months) where the compressed 40 and 50% (w/w) NAP/PVP-VA 64 solid dispersions showed less crystallinity than the uncompressed samples. This suggests that compression improved the physical stability of the solid dispersions as a result of enhanced drug-polymer interactions.
固体分散体优先被制成片剂和胶囊等固体剂型。在喷雾干燥后的制造过程中，固体分散体的结构稳定性尚未得到充分研究。在本文中，我们描述了压缩力对通过喷雾干燥制备的由萘普生和PVP-VA 64组成的固体分散体的影响。对含有30%（w/w）萘普生的固体分散体进行压缩，导致在2θ = 16.11°处粉末X射线衍射（PXRD）晕环图案最大值的强度较低，并且在室温下75%相对湿度储存21天后，未压缩样品的玻璃化转变加宽程度也高于压缩样品，这表明固体分散体发生了结构变化。对于压缩样品，源自萘普生羧酸部分的氢与PVP-VA 64的酰胺羰基部分之间相互作用的1654 cm⁻¹处振动带的强度增加。在长期稳定性研究（5个月）后，压缩的40%和50%（w/w）萘普生/PVP-VA 64固体分散体的结晶度低于未压缩样品，压缩的影响进一步放大。这表明压缩由于增强的药物-聚合物相互作用而提高了固体分散体的物理稳定性。
