Research On The Combination Of Hydrophilic Matrices And Membrane Control For Extended-release Of Water-soluble Drugs

Ambroxol hydrochloride was first producted by Germany Boehringer Ingelheim,in 1978.Ambroxol hydrochloride is a water-soluble model drug,which belongs to BCS I.To explore the potential utility of combination of hydrophilic matrix with membrane-controlled technology,the present study prepared extended-release tablets of ambroxol hydrochloride,through process of direct compression and spray coating.Hypromellose,Surelease~?and Opardy~?was selected as matrix material,barrier and pore former,separately.This study established and validated analytical methodology for the quality control of ambroxol hydrochloride sustained-release tablets,including cumulative release and assay.With the cumulative release as main index,Single factor experiments were accomplished to optimize the formulation.The type and amount of filler,the hardness range of the tablet and the coating curing time were selected.Various release rates could be easily obtained by adjusting the viscosity and amount of hypromellose,pore former ratios in coating dispersions and coating weight gains.Dissolution profiles of coated tablets displayed initial delay,followed by near zero-order kinetics.The tablets were tested by reciprocating cylinder.The results indicated that the application of coating film could make drug release more robust.The results of stress testing showed that the formulation had good stability.However,humidity should be controlled during storage of tablets.The study also established and validated an LC-MS/MS method for determining the blood concentration of ambroxol hydrochloride in Beagle dog plasma.In vivo pharmacokinetics was then performed to evaluate the necessity and feasibility of further development of this simple process and low cost approach.The pharmacokinetic study of different formulations showed that lag time became longer as the permeability of coating membrane decreased,which was consistent with the in vitro drug release trend.Besides,DAS 3.2.2 software was used to calculate the in vivo absorbance(Fa),and linear regression was performed with the corresponding in vitro cumulative release(Ft)to obtain the in vivo and in vivo correlation.The results indicated that coated tablets exhibited a good correlation between in vitro release and in vivo absorption.The results,therefore,demonstrated that barrier-membrane coated matrix formulations were extremely promising for further application in extended-release of water-soluble drugs.