Amorphous carbamazepine stabilization by the mesoporous silicate SBA-15

The poor solubility carbamazepine (CARBA) is the main responsible for its low and variable bioavailability. This problem is strictly connected to the high energy required for CARBA crystal lattice disruption that represents the rate determining step of the dissolution process. CARBA dissolution enhancement can be achieved by converting the crystals ordered structure in the amorphous solid state in which the molecules show a high mobility, requiring less energy for intermolecular bond breaking. Unfortunately CARBA amorphous form is unstable and turns into the crystalline one. The aim of this work was the improvement of CARBA dissolution by its conversion in the amorphous form and its stabilization by inclusion in the mesoporous silica material SBA-15. CARBA was loaded by a simple, safe and eco-friendly method obtaining a high final drug loading (40% wt.). The obtained inclusion product showed improved drug dissolution and good physical stability in comparison to crystalline CARBA. Interesting results were obtained also for the physical mixture of SBA-15 and CARBA which showed an increase of drug dissolution. Moisture effects on drug amorphous form stability are discussed as well. (C) 2013 Elsevier Inc. All rights reserved.