| Fluvoxamine maleate(FLM), commonly used in clinical depression and related symptoms and the treatment of obsessive-compulsive disorder. Because of depression, obsessive-compulsive disorder patients usually require long-term medication, to the multiple dosing of drugs, the fluvoxamine maleate sustained-release preparation can be used to reduce the frequency of administration, thus greatly improving the patient’s medication compliance; at the same time, it can be used to provide a smooth, long-lasting effective blood concentration, and avoid or reduce concentration fluctuations. Then the preparation of FLM will improve the safety of drug, reduce adverse drug reactions. And the present, there is no research on FLM sustained-release formulation, development fluvoxamine maleate sustained-release pellets capsules can play a better effect.The relationship between particle size and water content of the pellets was investigated with microcrystalline cellulose, the results showed that pellets prepared by centrifugal granulation, the water content of pellets was closely related to particle size. When moisture content of the material was about 35%, it should be stopped for liquid, otherwise, in the next few minutes, the particle size growth becomes uncontrollable. Pellets yield, friability, bulk density, angle of repose and particle size distribution were used as evaluation to examine the influences of liquid supply rate, blast frequency, rotary speed, air temperature, spray pressure and rounded time on the physical state of pellets, each single factor influence trends were prepared the foundation for the pellets.The UV spectrophotometry was established to determine the in vitro release of FLM and HPLC method was established to determine the content of the FLM. Preformulation studies showed FLM powder can be dissolved in 5min more than 85%, it was considered that the rate and extent of FLM absorption in vivo was not affected by the rate of gastric emptying. Decomposition products does not affect the determination of the main substance of the FLM. During the preparation of FLM pellets, high temperatures and iron vessel should be avoided, in order to provide a reliable basis for the subsequent analysis.The FLM matrix pellets were prepared with centrifugal granulation, the prescription was selected as 30% FLM, 20% HPMC K15 M, 5% lactose and 45% microcrystalline cellulose. An orthogonal experiment was designed to optimize the preparation process, the optimal process was a liquid supply rate of 10-6m L?min-1, blast frequency 5-7Hz, rotary speed 12-14 Hz, roll balls time was 18 min. In vitro release profile of the pellets conform Higuch equation.The FLM film-controlled pellets were prepared with centrifugal granulation, Coating materials, anti-sticking agents, opacifiers, induced pore-forming agent was investigated and an orthogonal experiment was designed to optimize the prescription, the best prescription was 33 ml NE 30 D, NE 30 D solid content: Talc was 1: 0.9,1.18 g DCP and the amount of titanium dioxide to form 100 ml coating solution for 100 g pellets. An orthogonal experiment was designed to optimize the liquid supply speed, wheel speed, blowing frequency, atomization pressure, and the best process was to fixed the air temperature at 45 ℃, the liquid supply rate of 4 m L?min-1, the frequency of the blast was 6Hz, rotary speed was 4Hz, atomization pressure was 0.20 Mpa. Pellets release fitting comply Ritger-Peppas equation. The stability study of membrane-controlled pellets showed that the system FLM pellets should be stored away from light and cool, dry place. |
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