Preparation Of Dextromethorphan Hydrobromide Floating Sustained Release Tablets

The ?oating drug delivery systems designed on the basis of hydrodynamically balanced system, which enable prolonged and continuous input of the drug to the upper parts of the gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new strategy is proposed for the development of gastroretentive dosage forms for dextromethorphan hydrobromide (DMB) preferably once daily. The design of the delivery system was based on the sustained release formulation, with ?oating and swelling features in order to prolong the gastric retention time, reduce the dosage frequency and increase patient compliance.According to the literature, ultraviolet spectrotometry method was developed for determination the release of DMB during the study of in vitro release. High performance liquid chrmatograhy (HPLC) method was developed for assaying the content of DMB in the DMB sustained-release (SR) floating tablet. The analytical methods above were proved to be simple, reliable and sensitive. In the floating test, different concentrations of hydrochloric acid solution (pH 1.2, 3.0, 5.0) were used as floating medium. The ?oating lag time and the total ?oating time were seleceted as determination index. These researches provide a reliable basis for the next formulation study and stability study.Basing on the preformulation study, influence of formulation and manufacture on the drug release and ?oating characteristics was investicated and an orthogonal experiment design method was used to select the optimized formulation. The optimized tablets were prepared by wet granulation method using hydroxypropyl methylcellulose (HPMC) K4M as hydrocolloid gelling agent (25 mg), sodium bicarbonate as gas-generating agent (20 mg), hexadecanol as ?oating assistant agent (18 mg), microcrystalline cellulose (MCC) and lactose as bulking agent, 4% ethanol solution of ethylcellulose (w/v) as binding agent. The prepared tablets could ?oat within 3min and maintain for more than 24 h. Drug release at 12 h was more than 85%.The data of physical parameters like weight, hardness, friability and drug content were all lie within the limits.The release mechanism of DMB was studied by comparing with Zero-order Model, First-order Model, Higuchi Model, Hixson-Crowell Model and Ritger-Peppas Model. Release data was in good linearization with the First-order Model and the prevailing release mechanism was diffusion with erosion as a supplementary release mechanism. Stability studies of DMB on light, temperature and moisture were determined and accelerated test and long-term test was taken to estimate the stability of the floating tablet. The results showed that appearance, content, drug release, and flotation were all stable under these tests.