Physicochemical Characterization of Phenobarbital Polymorphs and Their Pharmaceutical Properties

Abstract

Simple and reproducible methods of preparing six modifications (forms A, B, C (monohydrate), D (dioxane solvate), E (hemihydrate) and F of phenobarbital were established from those previously reported. The physicochemical properties of these modifications were measured using X-ray diffractometry, Fourier-transformed infrared spectrophotometry, differential scanning calorimetry, thermogravimetry, scanning electron microscopy, solubility and others. The dissolution properties of all modifications in JP XI, 1st fluid (pH 1.2) were evaluated at 37°C containing 0.5% gelatin to prevent polymorphic transformation during the test. Forms A and D showed comparatively higher solubilities among all modifications. The tapping rate constants (k) of all crystal forms were estimated based on Kuno's equation, the k value for form F being the largest, whereas that of form D, the smallest, and the order of k of magnitude of the constant was F > B > E > C > A > D. The tablet hardness after compression at 1000 kg/cm² depended on the polymorphic form. Form D was the hardest, while forms B and F were the softest, in the order D > A > C > E > B = F.