Solubility and stability of lorazepam in bile salt/soya phosphatidylcholine-mixed micelles

In the present study, the solubility and stability of the drug lorazepam, w hich was solubilized in bile salt/soya phosphatidylcholine-mixed micelles ( BS/SPC-MMs), were investigated. The solubility of lorazepam could be enhanc ed substantially in different bile salts and also in sugar ether, whereas t he solubility in Pluronic F68 (Pl.F68) was of lower order. Moreover; the ad dition 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 tha t lorazepam degradation followed apparent first-order degradation kinetics in phosphate buffer, as well as in the BS/SPC-MM, with highly enhanced stab ility 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 d egrees C, a shelf stability of about 10 months could be calculated for BS/S PC-MM at 5 degrees C. The solubility studies in BS/SPC-MM showed a recrysta llization and a polymorphic transition from modification II to I.