Effect of varying quantities of polymer on preparation and stability evaluation of carbamazepine cocrystals with dicarboxylic acid coformers.

The current study is an attempt to explore the effect of varying quantities of hydroxypropyl cellulose (HPC) polymer on carbamazepine (CBZ) cocrystal formation with dicarboxylic acid coformers i.e., malonic acid (MA), succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The cocrystals were first prepared without polymer by slurry crystallization method and then tried with different quantities of the polymer. The prepared samples were characterized by Powder X-ray Diffraction (XRPD). The characterization results indicate that in methanol pure carbamazepine-malonic (CBZ-MA) and carbamazepine-adipic acid (CBZ-AA) cocrystal can be prepared, while in ethanol and acetone pure carbamazepine-succinic (CBZ-SA) and carbamazepine-glutaric acid (CBZ-GA) cocrystals can be obtained respectively. The same cocrystals were tried using HPC polymer in three different quantities. The characterization results showed that a higher quantity of HPC polymer transforms CBZ-MA cocrystal polymorph-I to polymorph-II. The CBZ-SA and CBZ-GA cocrystal formation somehow inhibited as the concentration of HPC polymer increases. But on the other side, the formation of CBZ-AA cocrystal utterly not inhibited in the presence of varying quantities of HPC polymer. Furthermore, 11 different quantities of HPC were tried to know about the inhibitory concentration of HPC on CBZ-AA cocrystal formation. The CBZ-AA cocrystal preparation was not inhibited even at higher quantities of HPC compared to the coformer. Additionally, the effect of three different quantities of HPC on the thermal stability of the CBZ-AA cocrystal was investigated. Moreover, the stability of pure CBZ at 92% relative humidity (RH) condition was compared to CBZ-AA cocrystal with and without HPC polymer. The CBZ-AA cocrystal with and without HPC polymer was more stable than pure CBZ.