Optimization And Quantitative Control On Process Variables In Centrifugal Granulation

Centrifugal granulation is an advanced method of producing drug-layered pellets. The main purpose of the present study was to investigate the effect of process variables on properties of pellets in MCC beads preparation. With the Metformin Hydrochloride as model, drug-layered pellets were prepared in solution/suspension layering and powder layering. Additionally, the feasibility of centrifugal granulating technique for preparing matrix pellets were also studied.The common fillers were identified and evaluated in order to find the suitable initial material. The effect of the five independent process variables (rotor rotation speed, slit air flow rate, flow rate, spray air pressure and the temperature) on the expected yield, mean size and shape characteristics were studied using single factorial design. The results suggested that MCC be the best starting material for preparing by the centrifugal granulating process and pellets size prepared by this method was between 60 to 10 mesh. The amount of water and spray flow rate behave a crisscross effect on pellet size distribution.With the same mount of water,the pelltets size distribution became larger as the spray rate raised. The best ratio of MCC to water was between 1.2 and 1.4. The rotor rotation speed was found to have no obvious effects on pellets formation but can influence the expected yield. The best slit air flow rate was 28L·min-1.A set of optimal process variables was made on the basis of exerimental data.As regards the drug-layering process, Drug-layered pellets with a spherical shape, higher density and flowability were obtained by increasing the rotor rotation speed and spray air rate. As the rotor rotation speed and the slit air flow rate were increased, both the amount of drug loss and the agglomerates increased. In addition to the main effects, there were some significant paired interaction between slit air flow rate and spray air as well as rotor rotation speed and slit air flow rate. The significance of both material and process parameters, however, should be taken into account in the preparation of pellets by this method. The technical parameter optimized by orthogonal design in the centrifugal process were that the flow rate is 8ml·min-1, the temperature is 55℃and the spray pressure is 0.6Bar.Considering the powder rate between 30～90g·min-1, the flow spray rate is supposed to be 60～160ml·min-1.Prepare the sustained-release matrix pellets by powder layering with the MCC pellets which size between 40 and 60 mesh as initial beads. The pellets prepared with HPMC K15M of 45% amount behave a good release profile and release rate in vitro was conformed to conform Higuchi equation.In conclusion, centrifugal granulation is a convenient and flexible technique for producing MCC beads and respective drug-layered pellets.