Effects of particle size and tapped density on the content uniformity of repaglinide - metformin fixed dose tablet combination

Abstract

The study proposes a solution to content uniformity problem of repaglinide-metformin HCl fixed dosetablet combination with optimization of particle size distribution and tapped density of repaglinide and metformingranules. The developed dosage forms contain less than 0.5% w/w repaglinide and more than 75% w/w metforminhydrochloride in the composition, resulting in content uniformity problems. A route for, minimizing susceptibility tosegregation during the tablet press operation, thereby improving content uniformity, was studied through adjustingthe particle size distribution and tapped density of the granules. In this study, a new specification in manufacturingmethod was developed for obtaining repaglinide and metformin granules with particle size distribution and tappeddensity properties optimized for tablet homogeneity. Specific particle size distribution and tapped density specificationsbetween metformin HCl and repaglinide granules were described as (i) particle size distribution (D90, D50 and D10) ofmetformin HCl granule should be less than or equal to three times of particle size distribution (D90, D50 and D10) ofrepaglinide granule; and (ii) tapped density of metformin HCl granule should be less than or equal to two times oftapped density of repaglinide granule. Assay and in vitro dissolution rate analysis were performed by validated HPLCmethods.