Release Characteristics of Commercially Available Ambroxol Hydrochloride Sustained-release Capsules:an in vitro and in vivo Study
The differences in formulations and manufacturing processes will lead to the distinct in vitro and in vivo release properties of sustained-release preparations.According to the standards of imported registered drugs,Chinese Pharmacopoeia and relevant guidelines,the in vitro release curves and ethanol-induced dose-dumping behaviors of ambroxol hydrochloride sustained-release capsules from four different domestic and foreign manufacturers were systematically evaluated.Because of the different drug release mechanisms,the 24 h cumulative release amount of the drug from wax-matrix sustained-release capsules(Mucosolvan® Retard)was only 25.6％,while the 4-6 h cumulative release amounts of the other three film-controlled sustained-release capsules were more than 85％.The differences of drug release were also found in other pH media and ethanol-induced dose-dumping studies.Therefore,Mucosolvan® Retard and one commercially available film-controlled sustained-release capsule were selected for further release studies in simulated gastro-intestinal fluids and pharmacokinetics studies in beagle dogs.In the fasted state simulated gastric fluid(FaSSGF)medium,the release of Mucosolvan® Retard and the film-controlled sustained-release capsules at 2 h were 16.0％and 67.2％,respectively.The pharmacokinetic results showed that the cmax of film-controlled sustained-release capsules was 1.41 times higher than that of Mucosolvan® Retard.The reason for the different in vivo release results was speculated to be related to faster release of film-controlled sustained-release capsules in the acidic medium of upper digestive tract.Finally,based on the BCS classification of ambroxol hydrochloride,the results of this study and the reported human pharmacokinetics results,the key factors for the consistent development of this generic products were discussed.
万方数据
维普
