title: 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.
  
  
  CONCLUSIONS
  Hence, brain microdialysis was successfully used to evaluate a dissolution rate enhancing formulation.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University , Jamaica, NY , USA.
authors.forename: Murali Mohan
authors.initials: MM
authors.lastname: Bommana
authors.forename: Bharat
authors.initials: B
authors.lastname: Kirthivasan
authors.forename: Abhijat
authors.initials: A
authors.lastname: Shikhar
authors.forename: Simerdeep Singh
authors.initials: SS
authors.lastname: Gupta
authors.forename: Emilio
authors.initials: E
authors.lastname: Squillante
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004298:Dopamine / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009536:Niacinamide / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013997:Time Factors; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D047408:gamma-Cyclodextrins; D009536:Niacinamide; D002220:Carbamazepine; D004298:Dopamine