PHYSICOCHEMICAL CHARACTERIZATION OF PHENOBARBITAL POLYMORPHS AND THEIR PHARMACEUTICAL PROPERTIES

Simple and reproducible methods of preparing six modifications (forms A, B, C (monohydrate), D (dioxane solvate), E (hemihydrate) and F of p henobarbital were established from those previously reported. The phys icochemical properties of these modifications were measured using X-ra y diffractometry, Fourier-transformed infrared spectrophotometry, diff erential scanning calorimetry, thermogravimetry, scanning electron mic roscopy, solubility and others. The dissolution properties of all modi fications in JP XI, Ist fluid (pH 1.2) were evaluated at 37 degrees C containing 0.5% gelatin to prevent polymorphic transformation during t he test. Forms A and D showed comparatively higher solubilities among all modifications. The tapping rate constants (kr 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 ha rdness after compression at 1000 kg/cm(2) 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.