Study On Nitrendipine Sustained-release Floating Microspheres

Oral ingestion is the predominant and most preferable route for drug delivery. People have tried a lot to develop oral sustained-release preparation in order to improve the bioavailability and decrease administration times. As far as the controlled drug delivery systems, it is necessary to control its dissolution rate from the preparation and prolong its residence time in the stomach. Nitrendipine was selected as the model drug to prepare floating hollow microspheres (microballoons) with emulsion solvent diffusion method. The aim of this paper is to prolong the drug's action time, decrease administration times and increase the bioavailability.Ultraviolet-visible spectrophotometry (UV) method was developed for in vitro assay of drug content in NTD microspheres and used to study the release of drug from the formulations. High-performance liquid chromatography (HPLC) method with UV detector was applied to determine the concentration of related substance of nitrendipine.The solvent evaporation-deposition method was selected to prepare the floating microspheres. Applying incorporation efficiency, efficiency, buoyancy and release profiles as main indexes, formulation factors and technology factors were investigated and optimized by the single factor test. The investigation on the drug release mechanisms indicated that drug release from microspheres accorded with non-Fick diffusion model. Results of stability studies on nitrendipine microspheres showed that the microspheres were stable when exposed to high temperature and high humidity, but sensitive to light. The accelerating test showed that the stability of the formulation was strengthened at dark place.The gamma scintigraphy of both the ^99mTc-labeled floating microspheres and non-floating microspheres were carried out in volunteers to comparing the gastric residence time. The gastric residence time (GRT) was 5.0 and 1.5 h, respectively.HPLC method was developed to quantify the drug plasma concentration of rabbits, and the studies of Pharmacokinetics were performed after oral administration of two formulations. The pharmacokinetic parameters of sustained-release floating microspheres and domestic tablets were as below: T_max were 6.67±1.21 and 2.58±0.80 h, respectively. C_max were 96.14±30.07 and 132.32±59.13 ng·ml^-1, respectively. AUC_0-t were 897.64±282.95 and 542.17±191.34 ng·h·ml^-1, respectively. The relative bioavailability of sustained-release floating microspheres was 166.01% compared with domestic tablets. In a word, the preparation of sustained-release floating microspheres of nitrendipine was feasible, and could achieve the primal purpose to prolong the drug's action time, decrease administration times and increase the bioavailability.