Solubility and Stability of Lorazepam in Bile Salt/Soya Phosphatidylcholine–Mixed Micelles

Abstract

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°C to 60°C, a shelf stability of about 10 months could be calculated for BS/SPC-MM at 5°C. The solubility studies in BS/SPC-MM showed a recrystallization and a polymorphic transition from modification II to I.

Key Words:

• Arrhenius Plot
• BS/SPC-MM
• Lorazepam
• Polymorphism
• Solubilization
• Stability
• Surface tension
• X-ray diffraction