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

Year 2021, Volume: 25 Issue: 3, 331 - 340, 27.06.2025

Onur Pınarbaslı , Gülistan Pelin Gurbetoğlu Bahar Köksel Özgen , Nagehan Sarracoglu , Asuman Aybey

https://doi.org/10.29228/jrp.23

Abstract

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

Keywords

Repaglinide , metformin HCl , fixed dose combination , content uniformity , particle size distribution , tapped density

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