Preparation And In Vitro Release Of Metformin Hydrochloride Gastric Floating Sustained Release Tablets

Object:The aim of this paper was to prepare a gastric floating sustained-release tablet and investigate the effects of excipients on floating behavior and drug release.The regular formulations have the problem in low bioavailability of drugs with narrow absorption windows and short half-lives after oral administration.In the experiments a sustained-release tablet had been prepared,and it can float in gastric juice to achieve localized release of drugs in the stomach and enhance drug bioavailability.In addition,the floating mechanism of tablets in the gastric liquid was explored to provide a basis for the experimental design of formulation floating tablets.Methods:Metformin hydrochloride was chosen as the model drug in the study.The influence of controlled release polymers,low-density materials and disintegrants on drug release and floating behavior were investigated with floating lag time(FLT),floating duration time(FDT)and the cumulative drug release as the main indicators.Gabapentin was selected as a model drug to verify the effect of excipients on floating behavior.The swelling and erosion of the tablets,tablet hardness and thickness were utilized to evaluate the performance of floating tablets in vitro.To explore the mechanism of drug release,the dissolution data is fitted using modeled of drug release through Origin2018 software.Results:HPMC with higher viscosity led to stronger ability of gel formation and slower hydration rate.The floating tablet made of HPMC with the grade of K100LV can hydrate fast,and float in a short time,but had a fast drug release.Carbomer with higher viscosity can absorb more water,and took a longer time to float.Tablets made of Carbomer 741 could start to float in 10 minutes,while those made of Carbomer 974 needed 20 minutes to do so.When HPMC was combined with Carbomer to prepare the floating tablets,it was found that the larger the ratio of HPMC to carbomer,the shorter floating lag time(FLT),which was from 1 hour to 10 minutes when the ratio was increased from 1:2 to 2:1.Xanthan gum,HPC and PEO are inferior to HPMC in gel forming and have a longer FLT.For the floating tablets prepared with these excipients at the ratio of 1:1 to Carbomer,the tablets of HPMC started to float in 30 minutes,the tablets of xanthan gum needs 1 hour to float to the surface of liquid,and the tablets containing HPC and PEO erode quickly,and can not float.Polyvinyl alcohol(PVA)and carboxymethyl cellulose sodium(CMC-Na)can be used as drug release modifiers.The disintegrants can shorten FLT of the floating tablet,10%PVPP as a disintegrant can decrease the FLT from 2 hour to 10 minutes.Low-density materials have limited power to decrease the FLT,however they can increase the floating duration time(FDT)significantly.Wet granulation has a significant effect on the hydration of HPMC,the higher the viscosity of HPMC,the greater the impact on hydration.The drug release of gastric floating tablets prepared by K100M through wet granulation was significantly faster than that of tablets through direct compression,and the drug release rate increased from 60.27%to 66.73%at 2 hour,and the FLT was extended from 10 minutes to 1 hour.Hardness has no significant effect on drug release,and has a great impact on floating behavior.When the hardness decreases from 80N to 60N,and the FLT is shortened from 25 minutes to 4 minutes.Drug release data of the floating tablets follow the Fickian diffusion law.The tablets prepared by K100M conforms to the R-P model,while tablets prepared by K100LV conforms to the first-order release model.Conclusion:When there is a large portion of API in the floating tablets,the floating of tablets mainly depends gel materials and swelling materials,the gel material should be selected in consideration of the swelling volume and water absorption weight.For the tablets with low portion of API,a low-density material can be appropriately added to change the inherent density of the tablet and shorten the FLT.Considering the flowability request of the bulk materials during tableting,wet granulation should be a more favorable process choice.In this research,a novel floating controlled release tablet formulation with release period up to 10 hours,was developed with HPMC K100LV and Carbomer 971,and the prepared floating tablet can start to float after immersed into fluid,and can keep floated for 10 hours.