Cocrystallisation of carbamazepine with ascorbic acid: impact of additives on morphology, thermal stability, and dissolution properties

In this study, an antisolvent cocrystallisation of the BCS II drug carbamazepine (CBZ) with ascorbic acid (ASC) was investigated, utilising ultrasonic horn and overhead stirrer methods in the presence of various additives such as Hydroxypropyl Methyl Cellulose (HPMC), Bovine Serum Albumin (BSA), Tween 80, and Sodium Dodecyl Sulphate (SDS). The objective was to examine the effects of these additives on the morphology, thermal stability, crystallinity, and dissolution behaviour of CBZ-ASC cocrystals. The newly formed CBZ-ASC cocrystal with a 1:1 molar ratio and 5% additive concentration was thoroughly characterised using X-ray diffraction, differential scanning calorimetry (DSC), and fourier transform infrared (FTIR) spectroscopy. The packing diagrams and FTIR analyses confirmed molecular interactions within the cocrystal structure. Interestingly, the CBZ-ASC cocrystal exhibited higher endothermic peaks (at 187 and 190 °C) compared to the individual starting materials (188.6 °C for CBZ and 192 °C for ASC) when synthesised using both ultrasonic horn and overhead stirrer methods as per the to DSC analysis. The addition of the aforementioned additives influenced the morphology of the cocrystals significantly. For instance, SDS resulted in a mixture of plate-like and needle-like cocrystals, while BSA, HPMC, and Tween 80 induced the formation of various structures such as plates, blocks, and plate-like shapes, depending on the method used (ultrasonic horn or overhead stirrer). Dissolution studies indicated a modest enhancement in the dissolution rate of the cocrystals (18-22%) in the presence of additives, although the increase was not significant compared to the cocrystals (10%) without additives. In summary, this research provides valuable insights into the controlled cocrystallisation of CBZ with ASC and elucidates the impact of different additives on the properties and morphology of the resulting cocrystals. These findings contribute to the understanding of cocrystal engineering and its potential applications in pharmaceutical development.