RESUMO
OBJECTIVE: Efficacy of a formulation of a poorly soluble centrally acting drug was evaluated by measuring dopamine responses using in vivo brain microdialysis. METHODS: Co-crystals (1:1) of carbamazepine and nicotinamide (CBZ-NCT) were complexed with cyclodextrins (γ-CDs) using supercritical fluid processing. Phase solubility and intrinsic dissolution were studied. Pharmacodynamic studies were performed on rats divided into three groups getting either CBZ-NCT in CD (20 mg/kg CBZ), pure CBZ solution or vehicle. A guide cannula was implanted to attach the microdialysis probe. Dialysate samples were analyzed for dopamine levels, which were compared between groups. RESULTS: The optimized CBZ formulation (5% w/w in γ-CD) with solubility - 10 mg/mL showed stepwise increase in dopamine response (maximum 250% of baseline) compared to neat CBZ or vehicle (p < 0.05). The pharmacokinetics of the drug required 30 min to elicit CNS response, which peaked at about 1.5-2 h. CONCLUSION: Hence, brain microdialysis was successfully used to evaluate a dissolution rate enhancing formulation.
