Development Of Dextromethorphan Developmentof Hydrobromide Sustained Release Tablets Hydrobromidesustained

Dextromethorphan hydrobromide is a safe and effective antitussive drug, which has acentral action on the cough center in the meduia and used in the treatment of all kinds ofcough in clinic. This drug is absorbed quickly after taking orally, but has a short half-life andthe recommended oral dose for adults is three to four times a day, the fluctuation of blooddrug level is comparatively large, which cause some adverse effects such as dry mouth,constipation, nausea et al. Therefore, sustained release dosage forms were necessarilydeveloped to avoid repeated administration. This dosage form is designed to decreaseadministration frequency and keep steady blood drug level. Combining with other excipients,a dextromethorphan hydrobromide sustained release tablet was prepared by usinghydroxypropyl methylcellulose as basic matrix material.According to the literature, UV spectrotometry was developed for the determination ofdextromethorphan hydrobromide during the study of release. We also developed aHPLC method for the determination of drug content and detection of in vivo blood druglevel. These methods were accurate and quick which coμLd meet the requirement of theanalysis perfectly.Basing on the studies of the influence of formulation and manufacture on the release,optimal formulation modified to release drug over 8 h was obtained by star point design–response surface optimization method and the optimal tablets administrated twice a day wasscreened.Stability studies of dextromethorphan hydrobromide demonstrated that light,temperature, moisture and air had little effect on the content and release behavior of thedrug. By accelerated test and long-term test we predicted the period of validity was twoyears.The release mechanism of dextromethorphan hydrobromide was studied bycomparing with Zero-order Model,First-order Model,Higuchi Model and Ritger-PeppasModel et al, Release data was in good linearization with the Higuchi equation with correlationcoefficient r value of 0.9963. The release data also fitted Ritger-Peppas equation withcorrelation coefficient r value of 0.9965 and n value of 0.4825, between 0.45-0.89, indicatingthat diffusion was the prevailing release mechanism with erosion as a supplementary release mechanism.A simple HPLC method with fluorometric detection was established for thedetermination of dextrorphan and levofloxacin was used as internal standard. The standardcurve was linear in the range of 10.1～2508.4 ng·mL-1 for dextrorphan with correlationcoefficient r value of 0.9947. The recovery, was meeting the requirement of the analysis ofthe blood drug.The pharmacokinetic of dextromethorphan hydrobromide sustained release tablets inthe subjects was evaluated in this study. The commercial immediate release tablets wereserved as the control. After of single oral administration of the two formμLation, AUC0-∞ofthe two dosage forms were 2472.12±281.42 and 2732.54±313.76 ng.h.mL-1, respectively. Tmaxwere1.75±0.71 and 3.63±0.52 h and Cmax were 628.76±64.69 and 454.02±23.85 ng·mL-1; t1/2were2.71±0.90 and 2.56±0.6 h, respectively; The relative bioavailability was 110.72±7.51%.The results showed that Cmax of dextromethorphan hydrobromide sustained release tabletwas lower than that of the immediate release tablet, but Tmax and MRT were longer than theimmediate release tablet, indicating the sustained-release characteristic of the sustainedrelease preparation.