Flow properties of selected pharmaceutical powders
In the pharmaceutical industry uniform flow of powders is one of the most important considerations in solid dosage manufacture. Improper feeding of powders from storage hoppers into dye-presses can lead to inconsistent product quality, causing economic and health impacts. Investigation into the properties affecting powder flow is crucial. There were four objectives of the current research: 1. To determine the effect of moisture on the flow (Jenike flow index, Hausner Ratio and Carr Index, static and dynamic angle of repose) of selected pharmaceutical powders. 2. To study the effect of particle shape and size on Jenike flow index for selected starch and pharmaceutical powders. 3. To determine the effect of mixture compositions on the Jenike flow index of ordered mixtures of selected pharmaceutical powders. 4. To develop a novel flowability tester based on electrical capacitance tomography (ECT) that measures the dynamic angle of repose of powders.To address the first objective, to determine the effect of moisture content on the flow of four pharmaceutical powders; an active pharmaceutical ingredient (API), aspartame, hydroxypropyl methylcellulose (HPMC), and Respitose® ML001 were selected. The API and Respitose® powders were found to be nonhygroscopic and were tested at near zero moisture contents only (in this case 0.31% and 0.19% respectively). Aspartame was tested at moisture contents of 0%, 2%, 5% and 8% and HPMC at moisture contents of 0%, 2%, 5% and 10%. Powder flowability was measured using the Jenike shear index, the Hausner Ratio, the Carr Index and the static and dynamic angles of repose. The Jenike flow index of aspartame increased from 0.885 to 3.65 with an increase in moisture content, which was attributed to the formation of large, round agglomerates. The Jenike flow index of HPMC decreased from 3.28 to 2.65 with an increase in moisture content, which was attributed to the increasing strength of liquid bridges. The Jenike flow index was the only flowability indicator to capture this complex behaviour. In order to address the second objective, five starches (cow cockle, barley, rye, rice and tapioca), as well as four pharmaceutical ingredients (an API, aspartame, HPMC, and Respitose® ML001), were characterised for size and shape, and then tested for flowability. Powder flowability was measured using the Jenike shear test, the most widely accepted flowability standard in the pharmaceutical industry. It was found that the Jenike flow index decreased linearly with decreasing aspect ratio and decreasing roundness for the powders investigated. It was also determined that particle shape had a greater impact on flowability than size for powders under 30 microns in diameter. To address the third objective, ordered mixtures of pharmaceutical powders were examined to determine their flowability. Six combinations of Respitose® ML001, hydroxypropyl methylcellulose (HPMC), and an active pharmaceutical ingredient (API) in varying concentrations were selected for investigation. Powder flowability was measured using the Jenike shear test, the most widely accepted flowability standard in the industry. The Jenike flow indices of the ordered mixtures were indistinguishable from the Jenike flow index of pure Respitose® at the alpha = 0.1 level.The fourth objective, to develop a novel flowability tester using electrical capacitance tomography to measure the dynamic angle of repose, was investigated at the same time as the effect of moisture content. It was determined that the results of the novel dynamic angle of repose tester did not correlate well with the Jenike shear test. More development is needed before the novel flowability tester is ready for industrial use. The Jenike shear cell remains the only acceptable flow test for complex flow behaviour.
powder flow, Jenike shear test
Master of Science (M.Sc.)