The Research Of Sustained-Release Preparations By Film Coating Control

Two drugs, soluble and insoluble, with entirely different characteristics werechosen as model drugs. The film coating prescriptions of sustained-release for solubleand insoluble drugs were made respectively, which are significant for sustained-releasepreparations making with film coating in theory. Using the improved coatingequipment, the quantitative parameters were chosen including the rotate speed of thecoating pot, the temperature in coating pot, the spray volume and the spray pressure,which provides the theoretic data for similar coating equipments in batch production.The quantification control for sustained-release preparations making can insure thedrug release in fixed time and fixed amount to solve the difficult problem of drugrelease instability of these kinds of preparations in production.The soluble drug, Metformin Hydrochloride as a model drug, was prepared tosustained-release tablets by film coating technology. On the former studies the tabletcore formulation was fixed, and then the further research was made on the formulationof Metformin Hydrochloride sustained-release tablets. The formulation factors ascharacteristics and amount of Eudragit(a crylic acid polymer) were studied, andanalysis methods wasmade, and the conditions of drug release in vitro such asmedium, rotate speed of paddle were researched for the effects on coating and drugrelease. Then the process variables were examined emphatically by orthogonal designtest. The result of variance analysis shows that four influencing factors have asignificant influence on the coating effect; the greatest is the spray pressure. Theoptimum conditions of the film coating for the sustained-release tablets are rotatespeed of the pan: 45r/rain; velocity of flow of the coating solution: 2.5mL/min;temperature in pan: 45oC; pressure of spray: 160Mpa. The optimum process andformulation of Metformin Hydrochloride sustained-release tablets with film coating technology was determined, which meets the design demand. Three batches of tabletswere prepared by optimized formulation and coating process to examine the repetitionof the prescription and the process. The basic stability of the tablets was carried outand the drug release mechanism of the sustained-release tablet was studied, too.On the process of Metformin Hydrochloride granules coated, firstly, theformulation factors such as amount, volume of coating liquor and Eudragit RSconcentration, the process variables including rotate speed of the pan, temperature inpan, velocity of flow of the coating solution and pressure of spray, and the conditionsof drug in vitro such as medium, method and rotate speed of paddle were examined tohave effects on coating and drug release through single-factor test. Focus on theprescription, and then obtained the particles coated prescription which release percentmeet standard basically.For insoluble drug, Nisoldipine as model drug was prepared to sustained-releasepellet by film controlled-release technology, first carrying nisoldipine on the vacantpellets and then coating with film. The formulation factors including types ofanti-adhesive, types of Eudragit, amount of Eudragit RL, EC and volume of coatingliquor were studied. The conditions of drug release in vitro including methods androtate speed of basket were tested. The optimized process of carrying drugs on vacantpellets was made. And the three important factors were found, the first is temperaturein coating pot, following by spray volume, and the least one is rotate speed of coatingpot. The temperature in coating pot and spray volume are major factors of affecting thedrug to adhere on vacant pellets. The best operating parameters of coating drugs onvacant pellets are rotate speed of coating pot: 45 r/min; spray volume: 0.9mL/min;temperature in coating pot: 45℃. Ethyl cellulose as coating material was chosen on thedrug pellets for the drug release control. The optimization of the process conditionsand prescription were studied with orthogonal design method. The main factors ofaffecting the quality of coated pellets are: spray pressure＞temperature in coatingpot>rotate speed of coating pot＞spray volume. The result of variance analysis showsthat four influencing factors all have a significant effect on the drug release. The bestoperating parameters of coating for Nisoldipine release control are rotate speed ofcoating pot: 40 r/min; spray volume: 1.2 mL/min; temperature in coated pot: 40℃;spray pressure: 120MPa. The prescription factors of affecting the drug release in vitroare the amount of ethylcellulose＞amount of polyethylene glycol 6000＞amount ofhydroxypropyl methylcellulose. The best prescription of film-coating is drug pellets core: 120g; EC: 0.7g; HPMC: 0.3g; PEG6000: 1.0g; aerosil: magnesium stearate (1:1):0.2g; distilled water: 10mL; 95％ethanol: 90mL. The result shows that thecoated-pellets have sustained-release characteristics obviously in vitro. Drug releasespeed is changed by adjusting the thickness of the film and the amount of solubleadditives.A soluble drug was prepared for sustained-release tablets and an insoluble drugwas prepared for sustained-release pellets by film coating technology according tosome former studying of these processes. Research of granules coating with a solubledrug was for the basic need to make double ingredients sustained-released tablets aswell. The results meet the requirement of designed experiments and achieverequirement of quantification control for sustained-release preparations making.