Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
Pharm Res. 2012 Jan;29(1):271-84. doi: 10.1007/s11095-011-0540-4. Epub 2011 Jul 22.
Understanding the critical factors governing the crystallization tendency of organic compounds is vital when assessing the feasibility of an amorphous formulation to improve oral bioavailability. The objective of this study was to investigate potential links between viscosity and crystallization tendency for organic compounds from the undercooled melt state.
Steady shear rate viscosities of numerous compounds were measured using standard rheometry as a function of temperature through the undercooled melt regime. Data for each compound were fit to the Vogel-Tamman-Fulcher (VTF) equation; kinetic fragility via strength parameter (D) was determined.
Compounds with high crystallization tendencies exhibited lower melt viscosities than compounds with low crystallization tendencies. A correlation was observed between rate of change in viscosity with temperature and crystallization tendency, with slowly crystallizing compounds exhibiting larger increases in viscosity as temperature decreased below T(m). Calculated strength parameters indicated all compounds were kinetically fragile liquids; thus, kinetic fragility may not accurately assess glass-forming ability from undercooled melt state.
A link was observed between the viscosity of a compound through the undercooled melt regime and its resultant crystallization tendency, indicating viscosity is a critical parameter to fully understand crystallization tendency of organic compounds.
在评估无定形制剂提高口服生物利用度的可行性时，了解有机化合物结晶倾向的关键因素至关重要。本研究的目的是研究从过冷熔体状态下有机化合物的粘度和结晶倾向之间的潜在联系。
通过标准流变学测量了许多化合物的稳态剪切速率粘度，作为过冷熔体区域温度的函数。对每个化合物的数据进行了 Vogel-Tamman-Fulcher（VTF）方程拟合；通过强度参数（D）确定了动力学脆性。
结晶倾向高的化合物的熔体粘度低于结晶倾向低的化合物。在粘度随温度的变化率与结晶倾向之间观察到相关性，结晶速度较慢的化合物在温度低于 T（m）时粘度增加较大。计算出的强度参数表明所有化合物都是动力学脆性液体；因此，动力学脆性可能无法从过冷熔体状态准确评估玻璃形成能力。
在过冷熔体区化合物的粘度与其结晶倾向之间观察到联系，表明粘度是充分了解有机化合物结晶倾向的关键参数。
