The effect of crystal forms of some barbiturates on their pharmaceutical properties. Part 1: Phenobarbitone.

ABSTRACT

Up to 13 polymorphic forms of phenobarbitone have been reported in the literature. By melting the commercial sample and cooling under specified controlled conditions, three polymorphic forms II, II, XII, and a mixed form of II and III were obtained. The interconversion of the different forms was studied by special procedures including suspension in water, heating, and heavy dry grinding. The hydrated form XIII and a new hydrated one, designated XIV, were produced by suspending different other forms in water. Heating was found to affect transformation from any form to form I. IR spectroscopy and hot stage microscopy were used for the identification of the different polymorphic forms. Initial dissolution rate studies were carried out on only five forms. The dissolution rate constants were in the following decreasing order II greater than III greater than I greater than XIV greater than XIII. Form II was found to dissolve at a rate constant about twice that of both hydrated forms.