Role of mesoporous silicates on carbamazepine dissolution rate enhancement

Carbamazepine is an antiepileptic drug characterized by poorly water solubility that affects negatively its bioavailability. In fact due to its low water solubility (<200 microgram/ml) and the need of high dose (200 mg pro dose), CARBA pharmacokinetic profile is irregular. After oral administration, it is slowly and irregularly absorbed through the gastrointestinal tract and generally the plasmatic peak has a time lag of 4-8 hours. Here we report on the ability of the mesoporous silicate MCM-41 to act as a vehicle able to improve the drug dissolution rate by preventing drug crystallization. Carbamazepine was adsorbed into nanopores of MCM-41 and the drug loaded MCM-41 was characterized by X-ray powder diffraction, N2 adsorption, FT-IR spectroscopy and thermogravimetric and differential scanning calorimetry analyses. Carbamazepine loading resulted 14% and the drug was not arranged in crystalline form. In vitro drug release results showed a remarkable increase of carbamazepine dissolution rate in all the different tested media. As this improvement is due both to the high specific surface area of loaded MCM-41 and to the lack of crystalline drug, storage stability studies at different environment conditions were conducted in order to investigate the ability of MCM-41 to prevent drug crystallization.No conversion of the adsorbed drug in the crystalline form was observed in the experimental storage conditions. This result is very relevant since the employment of both the amorphous form and the solid dispersions of this drug could not meet any commercial applications so far because of its limited physical stability that however is gained by the use of MCM-41.