Mixing of pharmaceutical powders with small-sized granules. II. Mixed state of small-sized granules and micronized powders (author's transl)

Abstract

Investigation was made on the rate and degree of mixing of a micronized lactose powder (containing eosine as tracer ; weight mean diameter, 17 μm) with small-sized lactose granules (177-500 μm) by using a vertical shaking vessel at a frequency of 150 cycle/min and the amplitude of 30 cm. The mixture was compressed in its intact state and the compressed sample was divided into 16 segments to measure individual powder content of these segments. The coefficient of variation with respect to the powder content was then calculated. Analysis of the particle motion has revealed that the granules were separated easily from the bottom of the vessel during mixing to cause a dispersion of the cohesive powder capable of floating only as agglomerates. At the initial stage of mixing, the agglomerates thus formed were random-mixed with the granules ; however the granule-intake by the agglomerate was observed to form agglomerate complexes. Through the special agglomeration process as such, the mixture was found to become homogeneous and the coefficient of variation gave the minimum of 4% (with the sample obtained by mixing for 1-2 min). Such a homogeneous mixture was formed at a powder content of 10%, but not at 5 and 25%. Prolongation of the shaking time over five minutes caused fine particles to be shaken off to sediment onto the bottom. The homogeneous mixture, formed intermediately as has been stated above, was obteined specifically in the system composed of a fine powder and small-sized granules whose cohesive and adhesive forces (0.022 and 0.026 dynes, respectively) were in balance ; the mixture is therefore different from a simple rendomized-mixture or from an ordered one.