Enhancing dissolution rate of carbamazepine via cogrinding with Crospovidone and hydroxypropylmethylcellulose

Abstract

Carbamazepine belongs to the class II biopharmaceutical classification system (BCS) which is characterized by a high per-oral dose, a low aqueous solubility and a high membrane permeability. The bioavailability of such a drug is limited by the dissolution rate. In order to increase the drug dissolution, its solid dispersions were prepared by the cogrinding technique using an insoluble but highly hydrophilic crospovidone and soluble hydroxypropylmethylcellulose (HPMC) as the carriers. The ratios of drug to carrier were 1:1, 1:5 and 1:10. Comparison of the dissolution of the drug from its cogrounds with that of the unground drug, its ground form and the corresponding physical mixtures revealed considerable differences. The percentage of drug dissolved during the first 30 min, (%D-30.), for the ground and coground drug was 75-95, whereas the %D-30. for unground drug and its physical mixtures ranged from 41-62. FT-IR spectra indicated no intraction between the drug and the carriers in the cogrounds. But reduced crystallinity of the drug in the ground and cogrounds was evident in the x-ray diffraction patterns. The decreased crystallinity together with a reduced particle size, enhanced deaggregation and increased wettability of the drug. This could be accounted for the increased dissolution from the cogrounds. From the dissolution point of view, the physical mixtures of HPMC were inferior to the cogrounds, but were slightly superior to the physical mixtures of crospovidone due to the solubilization effect of HPMC.