Influence of Simulated Gastrointestinal Fluids on Polymorphic Behavior of Anhydrous Carbamazepine Form III and Biopharmaceutical Relevance

S. B. Bhise; M. Rajkumar

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.

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