Abstract
The co-grinding technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental stand point, as the technique does not require any toxic organic solvents. The present work is an attempt to use d-glucosamine HCl (G-HCl) as a potential excipient to improve dissolution rate of carbamazepine (CBZ) from physical mixtures and co-grinding formulations. The effect of order of grinding on dissolution of CBZ was also investigated. Co-ground of drug and G-HCL were prepared using different ratios using ball mill. The samples were subjected to different grinding times. In order to investigate the effect of grinding process on dissolution behaviour of CBZ, the drug was ground separately in the absence of glucosamine. Then the mixture of ground CBZ and un-ground d-glucosamine HCl were prepared. Physical mixtures of CBZ and G-HCl were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FT-IR, SEM, XRPD, and DSC. These results showed that the presence of glucosamine can increase dissolution rate of CBZ compared to pure CBZ. The results showed the order of grinding had a big impact on the dissolution performance of CBZ formulations containing glucosamine. All dissolution profiles generally showed that the fastest dissolution rate was obtained when ground CBZ was mixed with un-ground glucosamine. This was closely followed by the co-grinding of CBZ with glucosamine where lower grinding times showed the fastest dissolution. XRPD showed that the grinding of CBZ can reduce the percentage crystallinity of drug crystals. DSC study of ground CBZ showed that the grinding induced polymorphism transformations in the CBZ crystals and the limit and type of these transformations were related to the grinding time.
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