Solubility and stability of lorazepam in bile salt/soya phosphatidylcholine-mixed micelles
Solubility and stability of lorazepam in bile salt/soya phosphatidylcholine-mixed micelles
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DOI：
10.1081/ddc-100102190
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发表时间：
1999-01-01
影响因子：
3.4
通讯作者：
Müller, BW
中科院分区：
文献类型：
--
作者：
Hammad, MA;Müller, BW
本文研究了药物劳拉西泮在胆盐/大豆磷脂酰胆碱混合胶束（BS/SPC-胶束）中的溶解性和稳定性。劳拉西泮在不同胆汁盐和糖醚中的溶解度均显著增加，而在Pluronic F68（Pl.F68）中的溶解度较低。此外，将SPC加入到不同的BS溶液中大大提高了它们对劳拉西泮的增溶能力;这可能与所形成的MM降低表面张力的能力有关。稳定性研究表明，劳拉西泮降解遵循磷酸盐缓冲液中的表观一级降解动力学，以及在BS/SPC-MM中，后者系统中的稳定性大大增强。在三羟基BS的情况下，BS/SPC-MM的稳定效果高于二羟基BS。根据具有30 ℃至60 ℃温度范围内降解常数的Arrhenius图，可以计算BS/SPC-MM在5 ℃下约10个月的货架稳定性。在BS/SPC-MM中的溶解度研究显示从改性II到I的重结晶和多晶型转变。
In the present study, the solubility and stability of the drug lorazepam, which was solubilized in bile salt/soya phosphatidylcholine-mixed micelles (BS/SPC-MMs), were investigated. The solubility of lorazepam could be enhanced substantially in different bile salts and also in sugar ether, whereas the solubility in Pluronic F68 (Pl.F68) was of lower order. Moreover; the addition of SPC to different BS solutions greatly enhanced their solubilizing capacities toward lorazepam; this could be correlated with the ability of the formed MM to reduce the surface tension. The stability study showed that lorazepam degradation followed apparent first-order degradation kinetics in phosphate buffer, as well as in the BS/SPC-MM, with highly enhanced stability in the latter system. The stabilizing effect of BS/SPC-MM was higher in the case of trihydroxy BS than for dihydroxy BS. From an Arrhenius plot with degradation constants in a temperature range from 30 degrees C to 60 degrees C, a shelf stability of about 10 months could be calculated for BS/SPC-MM at 5 degrees C. The solubility studies in BS/SPC-MM showed a recrystallization and a polymorphic transition from modification II to I.