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Powder flowability is one of the key parameters in the pharmaceutical tabletting process. The flowability is affected by both the particles' properties and the tabletting equipment characteristics. Although it is generally accepted that powder flowability increases with an increase in particle size, quantitative studies and comprehensive theoretical insights into the particle property effects are still lacking. In this paper, ibuprofen, a non-steroidal drug widely used as an anti-inflammatory analgesic was chosen as a model material to assess the effect of particle properties on its flowability. Ibuprofen typically has a needle shaped morphology. The flowability of ibuprofen size fractions was studied in detail using two flow measurement methods. The separated fractions were also compared to magnesium stearate lubricated ibuprofen and its size fractions. The experimental results showed that powder flowability is significantly affected by both the particle size and size distribution. The finest size fraction that is separated from the bulk ibuprofen powder flows better than the bulk powder. For powders with narrow size distributions, the flowability increases significantly with the increase in particle size. In addition, admixing magnesium stearate to ibuprofen not only increases the flow function of the powder, but also reduces the internal friction angle. A theoretical analysis based on the limiting tensile strength of the powder bed was carried out and the flow conditions for particles of different size and shape were developed.

To quantify the crystallization of racemic ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] from aqueous ethanol it is necessary to know the growth rate kinetics. Growth rates were measured by adding SPG (size proportional growth) seed crystals to an isothermal non-nucleating batch crystallization and sampling during the batch. The supersaturation was measured by refractive index and the crystal size by laser light scattering (Malvern). To ensure the batch was non-nucleating the supersaturation was kept within the narrow secondary MZ (metastable zone). Measurements were made at three temperatures, 10, 25 and 40 °C. The growth rate was proportional (first order kinetics) to the solution supersaturation, expressed in mass ratio of ibuprofen to ethanol units. Despite the narrow MZ, the initial growth rates were substantial (up to 1 µm/min). Temperature has a large effect on growth rate with an activation energy of 13.7 kj/mol. The water content affects the growth rate coefficient differently depending on the temperature. [ABSTRACT FROM AUTHOR]