Konno Hajime, Taylor Lynne S
Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
Pharm Res. 2008 Apr;25(4):969-78. doi: 10.1007/s11095-007-9331-3. Epub 2007 May 23.
To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture.
Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose (HPMC) were exposed to different storage relative humidities and nucleation rates were measured using polarized light microscopy. Solid dispersions were further characterized using differential scanning calorimetry, infrared spectroscopy and gravimetric measurement of water vapor sorption.
It was found that the polymer additive reduced nucleation rates whereas absorbed water enhanced the nucleation rate as anticipated. When both polymer and water were present, nucleation rates were reduced relative to those of the pure amorphous drug stored at the same relative humidity, despite the fact that the polymer containing systems absorbed more water. Differences between the stabilizing abilities of the various polymers were observed and these were explained by the variations in the moisture contents of the solid dispersions caused by the different hygroscopicities of the component polymers. No correlations could be drawn between nucleation rates and the glass transition temperature (Tg) of the system. PVP containing solid dispersions appeared to undergo molecular level changes on exposure to moisture which may be indicative of phase separation.
In conclusion, it was found that for a given storage relative humidity, although the addition of a polymer increases the moisture content of the system relative to that of the pure amorphous drug, the crystallization tendency was still reduced.
研究在存在吸湿的情况下，各种聚合物抑制非晶态非洛地平从非晶态分子分散体中结晶的能力。
将非洛地平与聚维酮（PVP）、醋酸羟丙甲纤维素琥珀酸酯（HPMCAS）和羟丙甲纤维素（HPMC）的旋涂膜暴露于不同的储存相对湿度下，并使用偏光显微镜测量成核速率。使用差示扫描量热法、红外光谱法和水蒸气吸附重量法对固体分散体进行进一步表征。
发现聚合物添加剂降低了成核速率，而吸湿如预期的那样提高了成核速率。当聚合物和水都存在时，尽管含聚合物体系吸收了更多的水，但相对于在相同相对湿度下储存的纯非晶态药物，成核速率降低了。观察到了各种聚合物稳定能力之间的差异，这些差异可以通过组成聚合物不同吸湿性导致的固体分散体水分含量变化来解释。成核速率与体系的玻璃化转变温度（Tg）之间没有相关性。含PVP的固体分散体在暴露于湿气时似乎发生了分子水平的变化，这可能表明发生了相分离。
总之，发现在给定的储存相对湿度下，尽管添加聚合物相对于纯非晶态药物增加了体系的水分含量，但结晶倾向仍然降低。
