Chien Y W, Jefferson D M, Cooney J G, Lambert H J
J Pharm Sci. 1979 Jun;68(6):689-93. doi: 10.1002/jps.2600680608.
The effects of progesterone hydroxylation on silicone matrix drug release kinetics and thermodynamics were investigated. Hydroxylation at positions 11, 17, and/or 21 substantially reduced progesterone release. The magnitude of this reduction depended on the number and position of the hydroxy groups and could be attributed to decreased polymer matrix diffusivity (Dm) and polymer solubility (Cp). Thermodynamically, hydroxy group addition to positions 11 and/or 21 reduced the activation energy for matrix diffusion (Ed,m) but increased the solvation energy for dissolution in silicone polymer (delta HT,m)). Adding an hydroxy group to position 17 increased the Ed,m but decreased the delta HT,m. The overall (Ed,m) + delta H(T,m)) values were relatively constant and independent of hydroxylation.
研究了孕酮羟基化对硅酮基质药物释放动力学和热力学的影响。在11、17和/或21位进行羟基化显著降低了孕酮的释放。这种降低的幅度取决于羟基的数量和位置，可归因于聚合物基质扩散率（Dm）和聚合物溶解度（Cp）的降低。从热力学角度来看，在11和/或21位添加羟基降低了基质扩散的活化能（Ed,m），但增加了在硅酮聚合物中溶解的溶剂化能（δHT,m））。在17位添加羟基增加了Ed,m，但降低了δHT,m。总的（Ed,m）+δH(T,m)）值相对恒定，且与羟基化无关。
