Role of polymer chemistry in influencing crystal growth rates from amorphous felodipine
Role of polymer chemistry in influencing crystal growth rates from amorphous felodipine
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DOI：
10.1039/c001905d
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发表时间：
2010-01-01
期刊：
影响因子：
3.1
通讯作者：
Taylor, Lynne S.
中科院分区：
文献类型：
--
作者：
Kestur, Umesh S.;Taylor, Lynne S.
抑制有机无定形固体的结晶目前在制药领域引起很大兴趣，因为药物的无定形形式可以增强药物递送。已发现聚合物是许多有机玻璃和过冷液体的有效结晶抑制剂。本研究的目的是研究药物-聚合物氢键与晶体生长抑制之间的潜在相关性。使用各种聚合物制备疏水性药物模型非洛地平的淬火冷却样品：聚（乙烯基吡咯烷酮）（PVP）、乙酸琥珀酸羟丙甲基纤维素（HPMCAS）、聚（乙烯基吡咯烷酮）/乙酸乙烯酯（PVP/VA）和聚（乙酸乙烯酯）（PVAc）。在存在和不存在 3% w/w 聚合物的情况下，使用光学显微镜测量晶体生长速率作为温度（70-110 摄氏度）的函数。差示扫描量热法（DSC）用于评估玻璃化转变温度（T-g）和熔点。红外（IR）光谱用于探测药物-聚合物氢键相互作用。发现各种聚合物不同程度地抑制晶体生长。缓蚀效果的顺序为 PVP > PVP/VA > HPMCAS > PVAc，其中 PVP 是所用聚合物中最好的缓蚀剂。聚合物存在下的生长速率与高温下单独药物的生长速率相似，但随着温度降低而显着降低。药物-聚合物分散体的 T-g 与纯药物的 T-g 没有显着差异。药物-聚合物氢键相互作用的强度/程度的顺序为PVP > PVP/VA > HPMCAS >= PVAc。因此，能够与药物形成更强/更广泛氢键的聚合物似乎是更好的结晶抑制剂。
The inhibition of crystallization from organic amorphous solids is currently of great interest in the pharmaceutical field, since the amorphous form of the drug can enhance drug delivery. Polymers have been found to be effective crystallization inhibitors for many organic glasses and supercooled liquids. The objective of this study was to investigate potential correlations between drug-polymer hydrogen bonding and crystal growth inhibition. Quench cooled samples of a model hydrophobic drug, felodipine, were prepared with various polymers: poly(vinylpyrrolidone) (PVP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) and poly(vinyl acetate) (PVAc). Crystal growth rates as a function of temperature (70-110 degrees C) were measured using optical microscopy, in the presence and absence of 3% w/w polymer. Differential scanning calorimetry (DSC) was used to evaluate glass transition temperatures (T-g) and melting points. Infrared (IR) spectroscopy was used to probe drug-polymer hydrogen bonding interactions. The various polymers were found to inhibit the crystal growth to different degrees. The order of inhibition effectiveness was PVP > PVP/VA > HPMCAS > PVAc with PVP being the best inhibitor among the polymers used. The growth rates in the presence of the polymers were similar to those of the drug alone at high temperatures but showed a significant reduction as the temperature was reduced. The T-g's of the drug-polymer dispersions were not significantly different from that of the pure drug. The order of the strength/extent of drug-polymer hydrogen bonding interactions was PVP > PVP/VA > HPMCAS >= PVAc. Hence polymers which can form stronger/more extensive hydrogen bonds with the drug appear to be better crystallization inhibitors.