Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, USA.
Mol Pharm. 2010 Aug 2;7(4):1328-37. doi: 10.1021/mp1001153.
In this study, the ability of 7 chemically diverse polymers [Eudragit E100 (E100), poly(acrylic acid) (PAA), poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone-vinyl acetate) (PVPVA), poly(styrene sulfonic acid) (PSSA), hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose acetate succinate (HPMCAS)] to inhibit the crystallization of 8 readily crystallizable model compounds [benzamide (BD), phenacetin (PH), flurbiprofen (FB), flufenamic acid (FFA), chlorpropamide (CP), chlorzoxazone (CZ), bifonazole (BI) and lidocaine (LI)] was investigated. Films of the different drug-polymer combinations were prepared by rapid evaporation from solution, using a spin coating method. A total of 7 different drug/polymer weight ratios [90/10, 75/25, 60/40, 50/50, 40/60, 25/75 and 10/90 (w/w)] were evaluated for each drug-polymer combination. Crystallization behavior of the films was monitored using polarized light microscopy over 7 days of room temperature storage under dry conditions. It was observed that compounds having a higher crystallization tendency for the pure compound tended to be more difficult to stabilize using the polymeric additives; more polymer was required. In addition, the stabilizing ability of the polymers varied considerably for the individual compounds, with the acidic polymers PAA and PSSA showing the most extreme behavior. The acidic polymers were good stabilizers for the drugs with basic and amide functional groups, but extremely poor stabilizers for acidic drugs. A reasonable correlation between crystallization inhibition in spin coated films versus bulk powders (prepared by rotary evaporation) was observed. The small scale screening method is thus a potentially useful technique to evaluate the role of drug-polymer chemistry in the stabilization of amorphous solid dispersions.
在这项研究中，研究人员考察了 7 种化学性质不同的聚合物（Eudragit E100（E100）、聚丙烯酸（PAA）、聚维酮（PVP）、聚维酮-醋酸乙烯酯（PVPVA）、聚苯乙烯磺酸（PSSA）、羟丙基甲基纤维素（HPMC）和羟丙基甲基纤维素醋酸琥珀酸酯（HPMCAS））抑制 8 种易结晶模型化合物（苯甲酰胺（BD）、非那西汀（PH）、氟比洛芬（FB）、氟芬那酸（FFA）、氯丙酰胺（CP）、氯唑沙宗（CZ）、比呋唑酮（BI）和利多卡因（LI））结晶的能力。通过旋转涂层法，从溶液中快速蒸发制备不同药物-聚合物组合的薄膜。对于每种药物-聚合物组合，评估了 7 种不同的药物/聚合物重量比[90/10、75/25、60/40、50/50、40/60、25/75 和 10/90（w/w）]。在室温干燥条件下储存 7 天时，使用偏光显微镜监测薄膜的结晶行为。结果表明，对于纯化合物具有较高结晶趋势的化合物，使用聚合物添加剂更难以稳定；需要更多的聚合物。此外，聚合物对各化合物的稳定能力差异很大，酸性聚合物 PAA 和 PSSA 表现出最极端的行为。酸性聚合物是碱性和酰胺官能团药物的良好稳定剂，但对酸性药物的稳定性极差。在旋涂薄膜与旋转蒸发制备的块状粉末之间观察到结晶抑制的合理相关性。因此，这种小规模筛选方法可能是一种有用的技术，可以评估药物-聚合物化学在无定形固体分散体稳定化中的作用。
