title: Influence of Simulated Gastrointestinal Fluids on Polymorphic Behavior of Anhydrous Carbamazepine Form III and Biopharmaceutical Relevance.
abstract: The dissolution behavior and bioavailability of carbamazepine (CBZ) is rate-limited by formation of carbamazepine dihydrate (CBZ-D) in dissolution fluids. The present investigation involves formation and biopharmaceutical evaluation of CBZ-D obtained from simulated gastrointestinal fluids. The results obtained from solubility studies revealed that formation of CBZ-D was pH-dependent. The minimum solubility of 115 ± 1.7 mg/L obtained with simulated gastric fluid without pepsin indicates that the strongly acidic pH favors formation of CBZ-D and it was confirmed by the powder X-ray diffractography. Differential scanning calorimetry thermograms of samples revealed formation of CBZ-D and subsequent transition of CBZ form I. The percentage relative crystallinty for dihydrate was found to be 77.51%. Triton X present in fasted-state simulated gastric fluid (FaSSGF) increased the extent of crystallinty in dissolution media upto 86.50%. However, CBZ-D obtained from FaSSGF showed highest solubility of 335.36 ± 4.813 mg/L and dissolution of 36.74% in 60 min. This may be due to presence of surfactant on the surface of CBZ-D. The linear correlation was established between pH of simulated gastrointestinal fluids and percentage relative crystallinty with a correlation coefficient of 0.9904. CBZ form I had a better dissolution profile than any of the other polymorphs. Stabilization of CBZ form I in in vitro and in vivo conditions using pharmaceutical polymers in dosage form may bring better clinical outcomes than present-day therapies.
authors.affiliation: Biopharmaceutical Research Group, Department of Biopharmaceutics, Govt. College of Pharmacy, Karad, India.
authors.forename: S B
authors.initials: SB
authors.lastname: Bhise
authors.forename: M
authors.initials: M
authors.lastname: Rajkumar
mesh_terms: D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D011208:Powders; D012995:Solubility; D013501:Surface-Active Agents
chemical_list: D011208:Powders; D013501:Surface-Active Agents; D002220:Carbamazepine