Ibuprofen agglomerates preparation by phase separation.

The compression ability and dissolution rate of ibuprofen are poor. There are many processes to optimize these properties through adapted formulations. However, it would be more satisfactory to obtain directly during the crystallization step crystalline particles that can be directly compressed and quickly dissolved. This was the aim of this work. Ibuprofen spherical agglomerates were obtained using a very simple method based on the difference of solubility of ibuprofen in ethanol and in water. By cooling down an ibuprofen-saturated solution in an ethanol/water 50/50 mixture from 60 degrees C to room temperature under stirring, a phase separation occurs. Ibuprofen crystallizes in separated water droplets. After separation by sieving and drying, spherical agglomerates were obtained. A study of the physical properties of ibuprofen agglomerates was carried out using electron scanning microscopy and X-ray powder diffraction. The compression ability was tested using an instrumented tablet machine, and the dissolution rate was measured using continuous flow cells. An improvement in compression and dissolution properties of the spherical agglomerates produced was observed. The process of crystallization in a separated dispersed phase could be envisaged each time a drug exhibits opposite solubilities in two miscible solvents.

Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man.

The bioavailability of two oral formulations of trimipramine, tablets and solution, was performed in twelve healthy volunteers, in a cross-over study. Each formulation was administered in the morning after a fasted period, and in the evening after a meal, in order to evaluate the role of both administration time and food consumption on the plasma kinetic parameters, under usual therapeutic conditions. A high interindividual variability of data was found. First, the extent of bioavailability was identical for the two formulations but the rate of bioavailability seemed to be different, with the p.o. solution, being more rapidly absorbed (tmax = 1.50 h). The effect of administration time was more obvious for the solution as shown by a lower quantitative absorption as well as a delay in time to reach the maximal concentration. Regardless of formulation and administration time, the t1/2 beta was about 10 hours and the mean MRT value was 11 hours.