The primary prerequisites for powder mixtures/granules intended for tableting is to posses the quality of (i) homogenous composition; (ii) acceptable flowability, (iii) sufficient compressibility; and (iv) anti-adhesiveness. The most important prerequisite for these powder mixture/granulates is undoubtedly the ability to flow, due to its effect on product quality, especially dose and dosage form uniformity. A comprehensive literature study on the flowability of powders revealed that flow is affected by physical properties such as molecular- and interparticle forces, particle size and size distribution, particle shape, particle density, surface structure of the particle, and particle packing geometry. Various flow tests are available to determine powder flow, each measuring a variety of the properties mentioned above, resulting in different flow results and a subsequent variation in the classification of powders. Particle characterization of a wide range of pharmaceutical fillers through SEM and particle size analysis, indicated considerable differences between physical properties of the various fillers, which suggested significant differences in their flow behaviour. Flow tests were conducted determining the critical orifice diameter (COD); percentage compressibility (%C); angle of repose (AoR) and flow rate (FR) of the fillers in the absence and presence of a glidant (0.25% Aerosil® 200). The results confirmed the expected differences in flow obtained from the various tests, with no one of the fillers achieving the same flow behaviour in all the tests. The difference in flow amongst the fillers for a specific test could, to a large extent, been correlated with specific physical properties of the particles within the powder bed. COD results illustrated the influence of particle size and shape and surface structure on the flowability of these materials, with fillers with a smaller average particle size, less spherical shaped particles and uneven / rough surface structures performing poorer than their counterparts. The percentage compressibility (%C) of the materials was affected by the shape and size of the particles and the density of the materials, whilst the packing geometry also affected flow behaviour. Particles with high density and a low internal porosity tended to posses free flowing properties. Powders with a larger difference in the ratio between their respective bulk and tapped densities/volumes presented better flow results. The AoR of the fillers was affected by the cohesiveness and friction between the particles as well as the shape, surface structure and size of the particles. This method was less discriminative in terms of indicating differences in the flow of powders with comparable physical properties. A further drawback of this method was the variation in results between repetitions, which is affected by the way the samples were handled prior to measurement. The flow rate (FR) of the fillers was predominantly affected by the density of the materials and the size, shape, and surface structure of the particles. Powders with a higher density seemed to exhibit a better flow rate, although some of the other factors affected the flow rate more when the densities were very close or identical. The following general rank order for the various fillers (as an average of their performance in all the tests) were established (with no glidant present): Cellactose® 80 > FlowLac® 100 > Prosolv® HD90 * Ludipress® > Emcompress® >Avicel® PH200 > Starlac® » Emcocel® 50M * chitosan » lactose monohydrate. Addition of a glidant failed to change the rank order significantly. During the final stage of the study an attempt was made to modify and/or refine the composite flow index (CFI) proposed by Taylor ef a/. (2000:6) through (i) inclusion of flow rate results in its computation and/or (ii) varying the contribution (percentage) of each test to the CFI (Taylor & co-workers used equal contributions, namely 33 V* %, in their calculation of the CFI). The results indicated that including the results from the flow rate test was not beneficial in terms of providing a more representative CFI (in fact it reduced the accuracy of the index). Next various weight ratios for COD, %C and AoR was used to determine the CFI of each filler, and an optimum ratio was found at 50%:40%:10% (COD:%C:AoR) resulting in the highest CFI for each powder and the widest range for the CFI (largest difference between minimum and maximum values). This ratio was found in the presence and absence of a glidant. At this ratio the CFI discriminated well between the different powders in terms of their flowability. Lastly, the flowability scale for powders as used by the USP (20007:644) for %C and AoR results was adapted and fitted on the CFI results obtained for the various powders. This scale provided an exceptional fit for the powders both in the absence and presence of a glidant) and offered an excellent means for the grouping and classifcation of powders based on their CFI. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

The primary prerequisites for powder mixtures/granules intended for tableting is to posses the quality of (i) homogenous composition; (ii) acceptable flowability, (iii) sufficient compressibility; and (iv) anti-adhesiveness. The most important prerequisite for these powder mixture/granulates is undoubtedly the ability to flow, due to its effect on product quality, especially dose and dosage form uniformity. A comprehensive literature study on the flowability of powders revealed that flow is affected by physical properties such as molecular- and interparticle forces, particle size and size distribution, particle shape, particle density, surface structure of the particle, and particle packing geometry. Various flow tests are available to determine powder flow, each measuring a variety of the properties mentioned above, resulting in different flow results and a subsequent variation in the classification of powders. Particle characterization of a wide range of pharmaceutical fillers through SEM and particle size analysis, indicated considerable differences between physical properties of the various fillers, which suggested significant differences in their flow behaviour. Flow tests were conducted determining the critical orifice diameter (COD); percentage compressibility (%C); angle of repose (AoR) and flow rate (FR) of the fillers in the absence and presence of a glidant (0.25% Aerosil® 200). The results confirmed the expected differences in flow obtained from the various tests, with no one of the fillers achieving the same flow behaviour in all the tests. The difference in flow amongst the fillers for a specific test could, to a large extent, been correlated with specific physical properties of the particles within the powder bed. COD results illustrated the influence of particle size and shape and surface structure on the flowability of these materials, with fillers with a smaller average particle size, less spherical shaped particles and uneven / rough surface structures performing poorer than their counterparts. The percentage compressibility (%C) of the materials was affected by the shape and size of the particles and the density of the materials, whilst the packing geometry also affected flow behaviour. Particles with high density and a low internal porosity tended to posses free flowing properties. Powders with a larger difference in the ratio between their respective bulk and tapped densities/volumes presented better flow results. The AoR of the fillers was affected by the cohesiveness and friction between the particles as well as the shape, surface structure and size of the particles. This method was less discriminative in terms of indicating differences in the flow of powders with comparable physical properties. A further drawback of this method was the variation in results between repetitions, which is affected by the way the samples were handled prior to measurement. The flow rate (FR) of the fillers was predominantly affected by the density of the materials and the size, shape, and surface structure of the particles. Powders with a higher density seemed to exhibit a better flow rate, although some of the other factors affected the flow rate more when the densities were very close or identical. The following general rank order for the various fillers (as an average of their performance in all the tests) were established (with no glidant present): Cellactose® 80 > FlowLac® 100 > Prosolv® HD90 * Ludipress® > Emcompress® >Avicel® PH200 > Starlac® » Emcocel® 50M * chitosan » lactose monohydrate. Addition of a glidant failed to change the rank order significantly. During the final stage of the study an attempt was made to modify and/or refine the composite flow index (CFI) proposed by Taylor ef a/. (2000:6) through (i) inclusion of flow rate results in its computation and/or (ii) varying the contribution (percentage) of each test to the CFI (Taylor & co-workers used equal contributions, namely 33 V* %, in their calculation of the CFI). The results indicated that including the results from the flow rate test was not beneficial in terms of providing a more representative CFI (in fact it reduced the accuracy of the index). Next various weight ratios for COD, %C and AoR was used to determine the CFI of each filler, and an optimum ratio was found at 50%:40%:10% (COD:%C:AoR) resulting in the highest CFI for each powder and the widest range for the CFI (largest difference between minimum and maximum values). This ratio was found in the presence and absence of a glidant. At this ratio the CFI discriminated well between the different powders in terms of their flowability. Lastly, the flowability scale for powders as used by the USP (20007:644) for %C and AoR results was adapted and fitted on the CFI results obtained for the various powders. This scale provided an exceptional fit for the powders both in the absence and presence of a glidant) and offered an excellent means for the grouping and classifcation of powders based on their CFI. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.