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Analysis of particle deformation mechanisms and compact expansion during compaction on a high speed rotary tablet press

University of British Columbia

Pharmaceutical tablets are the most widely used dosage form and are prepared by the high speed compaction of powders or granules in a die on a rotary tablet press. The tablets produced must be coherent and capable of withstanding the stresses of handling and transportation. Successful compact formation depends on the ability of the particles to deform and form interparticulate bonds during compression in the die and the ability of these bonds to withstand elastic expansion during decompression and ejection from the die. Compaction on the high speed rotary presses used in the pharmaceutical industry normally occurs in less than 50 ms. The mechanisms of particle deformation during compaction are often analysed using presses operating at slow speeds or by using specialised equipment which perform tests on either preformed compacts or on single crystals. In the present work a sixteen-station rotary tablet press - a Manesty Betapress - was used to analyse high speed compaction. The analysis involved a study of the relationship between punch force and machine deformation, and its use in understanding the deformation of powder particles during compression and the elastic expansion of compacts during decompression. Rotary presses have been used to analyse compaction previously but either the materials were compressed under static conditions, or the results were obtained by complex viscoelastic modeling. These results were in error because the machine deformation was ignored when the punch displacement was calculated from the machine and punch-head geometry. In contrast, the relationship between machine deformation and punch force was used in this work to calculate punch displacements on the Betapress from the measurements of upper punch force. A previously reported method of calculating the punch displacement (Oates and Mitchell, 1989, 1990) was refined and simplified. This requires only the force versus time data where the force was measured by a strain-gauged upper roll support pin. Since it is relatively easier to measure punch force on a rotary press than make direct measurements of punch displacement, this method offers accurate punch displacement analysis without using complex instrumentation and/or geometric calculations. Over forty solids were studied on the Betapress. The solids were characterized for various physicochemical properties including true and bulk densities, and melting and/or decomposition temperatures. Powder X ray diffraction, melting points and a two-component melting pointcomposition phase diagram of R and S-ibuprofen showed that racemic ibuprofen is a one phase ‘racemic compound’ as opposed to a two phase ‘racemic mixture’. Thus, the USP description of ibuprofen as a ‘± mixture’ is misleading. All solids, including the commercially available S ibuprofen and racemic ibuprofen, were compressed on the Betapress under speed. The force signals from the upper roll support pin were collected as a function of time on a desk-top computer via an analog to digital converter. The compaction cycle was divided into compression and decompression phases by the dead centre position at which the punches are vertically aligned with the centres of the compression roll support pins. The force-time data were analysed using specially written software to obtain several parameters from the compaction cycle. Parameters obtained from the compression phase included peak offset time, decrease in punch pressure during peak offset time, porosity changes, work of compression and yield values of the solids. These parameters related particle deformation to pressure. The relationship between force and machine deformation was used to subtract the machine recovery from the total recovery during decompression. This gave a novel method of estimating tablet expansion during decompression. The tablet expansion data was used to calculate the work of tablet decompression and to estimate the Young’s modulus of several pharmaceutical solids. Since particle deformation during compression is dependent on strain rate, the strain rate during compaction was approximated by using the decrease in volume of the powder bed in the die during compaction, and this, along with the above parameters, was used to ascertain the deformation mechanism of each solid. The solids were categorised into groups ranging from low yield strength ductile solids such as acetylsalicylic acid, ibuprofen and their formulations to high yield-strength brittle solids such as the various calcium phosphates. The tableting parameters of formulated drugs and processed excipients were different from the parent samples. Racemic ibuprofen and S-ibuprofen showed little difference in their tableting parameters, hence a decision to use S-ibuprofen instead of racemic ibuprofen in tableting should be based on differences in other properties such as solubilities and pharmacokinetic differences. A simple and inexpensive method of analysing the behaviour of powder particles during compaction on a high speed rotary press using only force-time measurements is presented. This method is potentially applicable to any tablet press, and can be used for the in-process validation of compaction, for the quality control of raw materials, and for the development of new tablet formulations.

Thesis/Dissertation

application/pdf

2008-12-16

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http://hdl.handle.net/2429/2963

Pharmaceutical Sciences

University of British Columbia

UBCV

DSpace