DEVELOPMENT OF THE COMPOSITION OF GML-1 TABLETS OBTAINED BY WET GRANULATION: THE CHOICE OF A FILLER AND A BINDER

Introduction. The new original pharmaceutical substance (PS) N-benzyl-N-methyl-1-phenylpyrrolo[1,2-α]pyrazine-3-carboxamide (GML-1) that has anxiolytic activity has been synthesized at the V.V. Zakusov Research Institute of Pharmacology. Objective: to develop the composition and technology of GML-1-based tablets, by justifying the choice of excipients that allows the preparation of tablets of a required quality. Material and methods. The investigators studied the parameters of PS, which determined the choice of a technology for manufacturing tablets: namely: determination of the granulometric composition and shape of the crystals of PS GML-1, solubility and technological characteristics. The latter of PS GML-1 and model compounds were measured according to the procedure set out in the State Pharmacopoeia of the Russian Federation, 13th edition. The granulometric composition of PS was determined by the laser diffraction technique described in the pharmacopeia. The mathematical desirability function of Harrington was used for the statistical processing of the results. Results. The wet granulation method enables one to ensure uniformity of low-dose GML-1 tablets. It was established that excipients should be incorporated to optimize the technological parameters of PS. The moisture absorbing ability of the selected fillers and the choice of a binder for the preparation of a solution for moistening were examined. Conclusion. The optimal filler-binder combination is that of microcrystalline cellulose 101 and polyvinylpyrrolidone, which can minimize the disintegration time of a tablet that has a sufficient strength. This is confirmed by the calculated index of generalized Harrington’s desirability (D = 0.7031).