Showing papers on "High Shear Granulation published in 2009"

Monitoring and end-point prediction of a small scale wet granulation process using acoustic emission.

Abstract: A study to establish if acoustic emission could be used to monitor a small scale (120 g batch size) high shear granulation process and predict the process end-point, is reported. The robustness of the prediction model was further assessed by changing process variables. It is demonstrated that the technique is capable of repeatedly producing granules with consistent physical characteristics, such as particle size distribution and bulk density, despite changes in batch size and liquid dose rates. It is demonstrated that the model was affected by changes in impeller speed such that it was unable to identify a process end-point.

Comparison of low-shear and high-shear granulation processes: effect on implantable calcium phosphate granule properties

Abstract: Background: Calcium phosphate porous ceramics present a great interest not only as complex bone defect fillers but also as drug delivery systems. Most of the methods described in the literature to fabricate pellets are based on compaction, casting into spherical molds, or on processes such as liquid immiscibility or foaming. Despite wet granulation is used in a wide range of applications in pharmaceuticals, food, detergents, fertilizers, and minerals, it is not applied in the biomaterial field to produce granules. Methods: In this study physicochemical and in vitro drug delivery properties of implantable calcium phosphate granules, produced by two wet agglomeration processes, were compared. Pellets obtained by high shear granulation (granulation in a Mi-Pro apparatus) were shown to be more spherical and less friable than granules elaborated by low shear process (granulation in a Kenwood apparatus). Although Mi-Pro pellets had a slightly lower porosity compared to Kenwood granules, ibuprofen loading effici...

Difference in the lubrication efficiency of bovine and vegetable-derived magnesium stearate during tabletting.

Abstract: The purpose of this work was to evaluate and compare the functionality of bovine fatty acids-derived (MgSt-B) and vegetable fatty acids-derived (MgSt-V) magnesium stearate powders when used for the lubrication of granules prepared by high-shear (HSG) and fluid bed (FBG) wet granulation methods. The work included evaluation of tablet compression and ejection forces during tabletting and dissolution testing of the compressed tablets. Granules prepared by both granulation methods required significantly lower ejection force (p < 0.01) when lubricated with the MgSt-V powder as compared to those lubricated with the MgSt-B powder. Granules prepared by the HSG method and lubricated with the MgSt-V powder also required significantly lower compression force (p < 0.01) to produce tablets of similar weight and hardness as compared to those lubricated with the MgSt-B powder. The dissolution profiles were not affected by these differences and were the same for tablets prepared by same granulation method and lubricated with either magnesium stearate powder. The results indicate significant differences (p < 0.01) between lubrication efficiency of the MgSt-B and the MgSt-V powders and emphasize the importance of functionality testing of the MgSt powders to understand the impact of these differences.

Switch from single pot to multiphase high shear wet granulation process, influence of the volume of granulation liquid in a pilot scale study

Abstract: Among the high shear wet granulation equipments used in the pharmaceutical industry, two configurations are current: single pot process for which blending, granulation and drying are performed in the same apparatus and multiphase process that usually associates a mixer granulator and a fluid bed dryer. Pharmaceutical formulations are often developed with regard to a specific industrial apparatus, but production imperatives may require a switch to another type of equipment. In this work, granulation process switch was investigated at pilot scale on a first intention excipient formulation and with two drug substances chosen as model drugs on the basis of their different water solubility. Each one was tested at two concentrations, 1 and 25%. The volume of granulation liquid was first fixed at the same level whatever the granulation equipment and the formulation. In the second part of the study, the effect of the volume of granulation was highlighted. Regardless of the formulation tested, single pot granules, compared to multiphase one, had improved flow properties, compressibility and tablet cohesion but higher sticking phenomenon was observed when tableting. In the second part, the effect of an adjustment of the volume of granulation liquid for horizontal transposition between high shear granulation processes was discussed.

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

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