Effects of High-Shear Granulation on Granulate Homogeneity

Abstract

This study considers the effects of particle size of the powder constituents, and of impeller speed on the homogeneity of drug distribution on granulations produced in high-speed mixers. When a micronized low-dose steroid hormone was granulated together with unmicronized lactose in a Vactron75 high-shear granulator at 250 rpm, strong inhomogeneities of the drug distributionarose. The coarse particle size fractions of the granules were found to besuperpotent up to 150% of the mean drug content, whereas the fine size fractionshowed a corresponding subpotency of 50%. Both particle size and impellerspeed attributed to this phenomenon. At an impeller speed of 75 rpm, a significantlybetter drug distribution was obtained. Results show that the inhomogeneitiesfound are mainly a consequence of the balance between the impact pressureas exerted by the impeller on the one hand and the shear resistance of thenuclei on the other hand. At a speed of 250 rpm, the tensile strength of 3× 103 N/m2 ofthe initially formed nuclei is too weak to resist an impact pressure of 30× 103 N/m2. Forthat reason, particle rearrangement takes place, which results in inhomogeneity.Because an impeller speed of 75 rpm is equal to an impact pressure of 2.6× 103 N/m2, significantlyless demixing occurs. Similar results can be obtained when the particle sizeof all constituents is reduced, which increases the tensile strength of thenuclei.