In vivo brain microdialysis as a formulation-screening tool for a poorly soluble centrally acting drug

Abstract

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.

• Carbamazepine
• co-crystal
• dissolution
• dopamine
• pharmacodynamic
• solubility
• stereotaxic
• ventral hippocampus

Declarations of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

The authors acknowledge the financial support of the Pharmaceutical Sciences department of St. John’s University.