Quantified Control Of The Formulation And Process Parameters In Fluidized Bed Coating

Fluidized bed coating is the principal method coating on the dosage form with small particles, which includes top spray and bottom spray. In this paper, the parameters of technic process and formulation of these two methods coating on particles with three functions were investigated.Because the spray nozzle is farrer in fluidized bed top spray coating, the effect of technic process and formulation on the coating efficiency were investigated in both aqueous and organic solution formulation. Sand was selected as coating model, the orthogonal experimental results indicated:the amount of plasticizer was the most important effect on the coating efficiency in organic solution coating; in contrast, the atomized pressure was the most one in aqueous coating. This test had a instructive significance in top spray coating of the latter part in this paper.In the taste-masking coating on roxithromycin, roxithromycin was granuled by top spray method at first. The formulation and process were developed based on single-factor test, the optimized formulation were obtained by a central composite design:atomized pressure was 0.40bar, inlet temperature was 36～40℃, peristaltic velocity was 1.5g·min-1:theoretical weight gain was 10%, the amount of PEG6000 was 15%, the amount of talc was 20%. The average particle size was 250μm, the release of roxithromycin was below 38.5μg·ml-1 at 1 min, and almost complete at 10 min. The coated powder could be prepared as oral suspension or dispersion tablets.Top spray method was adopted for moistureproof coating. In order to protect hydrogen peroxide-inclusion compound from moisture regain, the crystal was coated first. The moisture-protect ability of several coating material were investigated and the product Opadry AMB which was based with PVA was selected. Because of its water-solubility, it had no effect of release profiles. The optimized process parameters were:atomized pressure was 0.40bar, inlet temperature was 45～50℃, peristaltic velocity was 1.2 g·min-1, solid content was 10% Opadry AMB. Coated crystal could be pressed successfully. And the bacteriostatic test indicated that the buccal tablets based on hydrogen peroxide-inclusion compound exhibited good bactericidal effect.Sustaind-release coating by fluidized bed bottom spray was investigated in the last chapter. The blank MCC pellets were prepared by centrifugal granulator, then coated with metformin hydrochloride. The pellets were coated with Eudragit RS/RL ethanol solution and Eudragit NE30D aqueous dispersion to be prepared sustaind-release pellets, parameters of the process and formulation were investigated. The optimized formulation was obtained by a central composite design in Eudragit RS/RL ethanol solution coating process:atomized pressure was 0.30bar, inlet temperature was 40℃, peristaltic velocity was 2.3 g·min-1:theoretical weight gain was 13%, Eudragit RS/RL 92:8, the amount of talc was 30%. The release character followed Higuchi equation. The pharmacokinetics of the sustained-release pellets in rabbits were studied. HPLC method was performed to detect the concentration of metformin in plasma and the parameters of pharmacokinetics were counted. The sustained-release pellets had a obviouse delayed Tmax and lower Cmax than uncoated pellets. Sustained-released pellets were correlative well with absorption percentage in vivo and release in vitro.The results indicated that these three functional coating had very good coating effects by quantified control of the formulation and process parameters.