Showing papers on "High Shear Granulation published in 2006"

Defining Scaling Criteria in High Shear Granulation

Abstract: Mandated changes in the way pharmaceutical manufacturers are developing products are being ushered by the Food and Drug Administration (FDA) for new drug applications and generic ANDAs. Prior to the phasing in of pharmaceutical quality assessment systems for submission review (chemistry, manufacturing and controls (CMC)) targeting implementation in 1Q2007 [1], development of solid products by granulation was and is still by and large an empirical, ‘look, touch and feel’ exercise. Barriers to progress in this area lay in the reluctance by industry to embrace new methods that may not be readily accepted by the FDA (the perception being that old proven methods were more likely to be accepted by the regulators); but barriers also existed and still exist because of the limited fundamental understanding of the complex materials behaviours and the many mechanisms at work in granulators. Pharmaceutical development requires an understanding of scale up behaviours in manufacturing processes based on predictive characterization of the way granules form via wetting and nucleation, the way granules grow viz a viz consolidation and coalescence and the way they break by attrition. This understanding, however, is in its naissance as the different mechanisms in play need to be separated and studied individually. Scale-up of high shear granulation, therefore in the pharmaceutical industry, has been approached in a number of ways [1-7]. Typically, impeller tip speeds were kept constant as a scale-up parameter (kinematically similar criterion). Froude number was also suggested a scale-up parameter (as a for dynamic similarity criterion) even for geometrically dissimilar granulators [4].

Designing granules for abrasive cleaning (using high-shear granulation).

Abstract: This work investigates the granulation of fine calcium carbonate powder to form microgranules (less than lOOf.lll1). The influence offormulation and operating conditions on granule properties was investigated. This work analyses experimental data using a database approach to relate granulation conditions to granule properties, to fmd propertyto-property relationships and to investigate the influence on the abrasion of Perspex. It was found that the granulation was undertaken in an unstable regime dictated by the need to produce small granules. As a result, it was not possible to achieve reproducibility in making the granules. For the range of granules produced it was difficult to determine variation in abrasiveness within the experimental errors, a detailed error analysis was carried out. A theoretical relationship between strength and porosity is developed and the factors influencing abrasive wear are investigated. Two theoretical models are presented: 1) Impact Failure model and 2) Granule Consolidation model. The impact failure model relates dynamic impact strength to static strength, which enables the prediction of a failure distribution curve (how many particles will fail per hundred impacts as a function of velocity). This is done using a "critical normal impact velocity" determined from the properties of the granule, properties of the impact surface and experimentally measured granule static strength. The granule consolidation model allows the qualitative prediction of the rate and extent of consolidation from granulation conditions. It models the compaction of a granule by descnbing the packing of its primary particles within an imaginary internal granule. Sphere packing is discussed with implications for determining the maximum packing of a primary particle size distribution.