SOLUBILITY AND RELATED PHYSICOCHEMICAL PROPERTIES OF NARCOTIC ANALGESICS
SOLUBILITY AND RELATED PHYSICOCHEMICAL PROPERTIES OF NARCOTIC ANALGESICS
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DOI：
10.1023/a:1015994030251
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发表时间：
1988-09-01
影响因子：
3.7
通讯作者：
FLYNN, GL
中科院分区：
文献类型：
--
作者：
ROY, SD;FLYNN, GL
考察了部分阿片类药物和苯丙哌啶类麻醉性镇痛剂的物理化学性质。测定了它们在正己烷和水中的溶解度，以及吗啡在其他有机溶剂中的溶解度。正规溶液理论似乎适用于吗啡在缺少强偶极子和氢键的溶剂中的溶解行为。根据吗啡在伦敦溶剂中的溶解度和理想溶解度确定了吗啡的最佳溶解度参数为13.2(卡/厘米~3)1/2。仅从吗啡正己烷的溶解度和熔融性质计算吗啡的S溶解度参数，得到相应的delta2值。这些测量的溶解度参数略大于由摩尔吸引常数估算的溶解度参数。根据正己烷的溶解度、熔点和熔化热计算了氢吗啡酮、可待因、芬太尼和舒芬太尼的溶解度参数，分别为11.7、10.9、9.8和9.7(卡/厘米~3)1/2。对于这些化合物，实验溶解度参数与由摩尔吸引常数估算的溶解度参数一致。由于度冷丁、芬太尼和舒芬太尼表现出低水平的晶体内凝聚力，低熔点和相对适中的熔化热反映了这一点，理论上预测的它们在有机溶剂中的理想溶解度比测定的吗啡及其类似物高得多。与溶解度一致的是，两个4-苯胺哌啶类似物和美比妥的辛醇-水分配系数比阿片类药物大几个数量级，证明了度冷丁、芬太尼和舒芬太尼比阿片类药物更亲油的事实。
The physicochemical properties of select opioid and anilinopiperidine narcotic analgesics were investigated. The solubilities of the nacrotics in hexane and water and, for morphine, in other organic solvents were determined. Regular solution theory seems to be applicable to the solubility behavior of morphine in solvents that lack strong dipoles and hydrogen bonds. A best-fit solubility parameter of 13.2 (cal/cm3)1/2 for morphine was determined from its solubilities in London solvents and its ideal solubility. Calculation of morphine''s solubility parameter from its hexane solubility alone and its melting properties gave a corresponding .delta.2 value. These measured solubility parameters were appreciably larger than the solubility parameter estimated from molar attraction constants. Solubility parameters of hydromorphone, codeine, fentanyl, and sufentanil were also calculated from respective hexane solubilities, melting points, and heats of fusion and were 11.7, 10.9, 9.8, and 9.7 (cal/cm3)1/2. For these compounds, experimental solubility parameters agreed with solubility parameters estimated from molar attraction constants. Because meperidine, fentanyl, and sufentanil exhibit low levels of intracrystalline cohesion, as reflected in low melting points and relatively modest heats of fusion theoretically projected ideal solubilities in organic solvents measured for them were considerably higher than determined for morphine and its analogues. Consistent with the solubilities, the octanol-water partition coefficients of the two 4-anilinopiperdine analogues and of merperidine were several orders of magnitude larger than those of the opioids, evidencing the fact the meperidine, fentanyl, and sufentanil are substantially more lipophilic than the opioids.