PURPOSE: Glibenclamide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Therefore, to enhance the drug dissolution, serum concentrations and its hypoglycemic effects, it was formulated as solid dispersions and evaluated the relevant in vitro and in vivo parameters. METHODS: The drug solid dispersions were prepared by solvent deposition technique using microcrystalline cellulose as the carrier in different ratios and their dissolution rates were compared to those of pure drug and its physical mixture with carrier. Drug serum concentrations and hypoglycemic effects in rabbits of pure drug, a physical mixture and the corresponding solid dispersion were investigated. In order to elucidate the observed in vitro and in vivo differences, IR spectroscopy and x-ray diffraction patterns of the formulations were studied. RESULTS: The solid dispersion with the drug to carrier ratio of 1:19 showed the highest dissolution rate with the dissolution efficiency (DE) of 44.42 in comparison to pure drug (DE = 3.82), physical mixture (DE = 4.91) and other solid dispersions (DE between 13.85-39.94) and also produced higher drug serum concentrations (more than 4 times at 6th hour post dose) as well as enhanced hypoglycemic effects relative to pure drug and its corresponding physical mixture. CONCLUSIONS: Solvent deposition technique was proved an effective tool of increasing dissolution probably due to enhanced wettability and reduced drug particle size, which in turn led to enhance drug serum concentrations and its hypoglycemic effects. Strong quantitative correlations were established between dissolution parameter and parameters related to serum concentrations as well as hypoglycemic effects.
PURPOSE:Glibenclamide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Therefore, to enhance the drug dissolution, serum concentrations and its hypoglycemic effects, it was formulated as solid dispersions and evaluated the relevant in vitro and in vivo parameters. METHODS: The drug solid dispersions were prepared by solvent deposition technique using microcrystalline cellulose as the carrier in different ratios and their dissolution rates were compared to those of pure drug and its physical mixture with carrier. Drug serum concentrations and hypoglycemic effects in rabbits of pure drug, a physical mixture and the corresponding solid dispersion were investigated. In order to elucidate the observed in vitro and in vivo differences, IR spectroscopy and x-ray diffraction patterns of the formulations were studied. RESULTS: The solid dispersion with the drug to carrier ratio of 1:19 showed the highest dissolution rate with the dissolution efficiency (DE) of 44.42 in comparison to pure drug (DE = 3.82), physical mixture (DE = 4.91) and other solid dispersions (DE between 13.85-39.94) and also produced higher drug serum concentrations (more than 4 times at 6th hour post dose) as well as enhanced hypoglycemic effects relative to pure drug and its corresponding physical mixture. CONCLUSIONS: Solvent deposition technique was proved an effective tool of increasing dissolution probably due to enhanced wettability and reduced drug particle size, which in turn led to enhance drug serum concentrations and its hypoglycemic effects. Strong quantitative correlations were established between dissolution parameter and parameters related to serum concentrations as well as hypoglycemic effects.
Authors: Eva C Arrua; Olga Hartwig; Duy-Khiet Ho; Brigitta Loretz; Xabier Murgia; Claudio J Salomon; Claus-Michael Lehr Journal: Pharm Res Date: 2021-05-17 Impact factor: 4.200