Process understanding on high shear granulated lactose agglomerates during and after drying

摘要: In 2001 the FDA launched Process Analytical Technology initiative as a response to growing public and industrial awareness that there is lack of process understanding required have an optimal control pharmaceutical manufacturing. The current research project was initiated based upon insight critical product attributes can only be acknowledged thorough understanding. This thesis seen follow up on earlier done wet high shear granulation; key parameters are involved in granulation process, including granule breakage growth were determined. Although relevance these towards formation inhomogeneous granules reported extensively, consequences described in-homogeneity phenomena further processing not elaborated. After drying step always necessary obtain basis for final drug product. but often involves unwanted uncontrolled size reduction. aim this investigate behavior throughout heterogeneity during after process. it shown granular composition, water content quality drying. Granule characterization revealed change (partially) dried follows three phase system characterized by growth, plateau phase. available surface enabling layering coalescence consolidation. Below minimum liquid bridge volume presence very small amounts or solid bridges cannot prevent abundant above content, with Rumpfs’ dynamic strength. More specific, fluid bed bed, size, inter-granular composition totally heterogeneous differentiates rate extent increase reduction different classes relation Near infrared spectroscopy (NIR) versatile method determine factors in-line monitoring attrition effects. By NIR led significantly compositions (non-crystalline crystalline lactose) direct influence functionality such compactibility. Finally, specific degradation steroid lactose concluded granulated dictates both chemical physical stability aspects granules.