Fluidized bed granulation of an ordered powder mixture.

The phenomenon of ordered unit segregation is of paramount importance in determining the homogeneity of an ordered mixture. This problem can be avoided by using a monodisperse carrier, but it is uneconomic. The fluidized bed granulation of a 0.1% ordered mixture has been studied as a method of reducing the effects of segregation. The ordered units were stable when fluidized and no significant loss of the microfine adsorbed material occurred during processing. The distribution of the minor component in the granules was significantly more uniform than in the original ordered mixtures. The demixing potential (formula: see text) (where p = proportion of cohesive minor component and w is the weight % of carrier material in a particular size range) was used to quantify the distribution of the minor component as a function of particle size. DP is a coefficient of variation and can be directly compared with the specification standard deviation sigma A. Batches of granules were compressed into 100 or 350 mg tablets, containing approximately 100 and 350 micrograms of model drug substance. The weight and content coefficients of variation (c.v.) were determined for 20 tablets. All batches had a weight c.v. less than or equal to 1.5% and a content c.v. less than or equal to 4.6%. Granulation of an ordered mixture greatly reduces the potential for segregation to decrease the mixture homogeneity. It also provides a solution to the problems which may be encountered when the mixing of small quantities of cohesive materials during conventional fluidized bed granulation is attempted.