Impact of Lubrication on tablet properties


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Investigation of Compression Behavior of a Co-processed Mixture of Corn Starch and Pregelatinized Starch as a Direct Compression Excipient AAPS Poster Nov 2009

The use of modified starch products as tablet excipients continues to grow, due to their multifunctional properties, wide regulatory acceptance and availability. The aim of this study was to investigate the compression behavior of a co-processed mixture of corn starch and pregelatinized starch (StarCap 1500®, co-processed starch excipient) under simulated rotary tablet press production conditions.

Matt Roberts (1), Jack Teall (1), Kevin Hughes (2), Ali R. Rajabi-Siahboomi (2)



Compaction of recrystallised ibuprofen Oct 15, 2009

Ibuprofen (_-methyl-4-(isobutyl)phenylacetic acid) was recrystallised from a range of solvents. Particle morphology, crystallinity, melting points and powder flow properties were evaluated. Additionally, the compaction properties of the ibuprofen control and recrystallised samples were assessed at different compaction forces and speeds, before and after blending with an equalamountof lactose, using a Stylcam® 100R rotary press simulator. Recrystallised ibuprofen samples displayed equal or better tablet strength than the control, whilst ibuprofen recrystallised from acetone had improved flowability and ibuprofen recrystallised from 2-ethoxyethyl acetate exhibited lower levels of elastic energy during compaction. Additionally, when formulated with lactose, recrystallised ibuprofen samples displayed lower punch adhesion levels, particularly at a low compaction force.

L. Seton (1), M. Roberts (1), F. Ur-Rehman (1)



The effect of spray drying on the compaction properties of hypromellose acetate succinate July 13, 2010

The aim of this study was to evaluate the compaction behavior of a model two-component amorphous spray-dried dispersion system compared with the unprocessed excipients, using simulated rotary tablet press production conditions. Method: In this study, the stabilizing polymer, hypromellose acetate succinate (HPMCAS), was solubilized and spray dried with and without sodium lauryl sulfate (SLS). The impact of compression force and speed on the tabletting process was quantified by means of tablet tensile strength, compaction energy, and Heckel analysis. Results: Addition of the surfactant SLS, spray dried or as a physical mix, reduced the tablet strength. However, a lesser impact on the unprocessed excipients was observed in comparison with the spray-dried excipients. In the presence of 1% (w/w) SLS, tablets displayed a tendency to cap when compressed at higher speeds, supported by high elastic energy values indicating high uni axial stress upon decompression. In the presence of 3% (w/w) SLS, tablets could not be produced at high speeds. Heckel analysis revealed a greater strain rate sensitivity of HPMCAS when spray dried in the presence of surfactant. Exposure of samples to a range of relative humidities before compaction had no effect on tablet strength. Conclusion: This study has shown that spray drying of HPMCAS in the presence of a surfactant affects the compressibility of the material, resulting in decreased tablet strength, increased elastic deformation, and capping.

Matthew Roberts (4), Touraj Ehtezazi (4), Ann Compernolle (3), Ketan Amin (3) The influence of the STYLCAM Flowmatic feed system on tablet properties The aim of the current investigation was to examine the influence of the flowmatic feed system and the STYLCAM 100R rotary press simulator production speed on the weight uniformity and tensile strength of tablets produced from formulation exhibiting different flow characteristics

Dr M Roberts (1), Dr J. Gilmartin (1)



Evaluation of Engineered Spherical Lactose Particles for Direct Compression using the STYLCAM 100R

The aim was to produce spherical lactose particles (EL) using a novel crystallization technique and to compare their compaction properties with commercial lactose (CL) and microcrystalline cellulose (Avicel PH102).

H. Larhib (1), M. Roberts (1), H Hebet (1), A. M. Dyas (1), J.L. Ford (1)



Development of Hydrocortisone Mini-Tablets for Improved Paediatric Dosing

An improvement in the accuracy of paediatric dosing of hydrocortisone over the practice of manipulating ‘adult’ dosage forms by quartering tablets has been highlighted during this study. The feasibility of industrial scale production of hydrocortisone mini-tablets, with good weight uniformity and consistent dissolution performance has been demonstrated.

M. Roberts (1), F. Mohamed (1), R. Saleem (1), U. U. Shah (7), L. Seton (1), J. L. Ford (1)



Diluent Effects On Drug Release From Sustained Release Compritol® 888 ATO Tablets UK Pharm SCI poster

Introduction: Glyceryl behenate (Compritol® 888 ATO) is commonly used in formulating sustained-release lipid matrices [1]. When compressed, Compritol® 888 ATO forms an insoluble network structure, allowing water to penetrate and subsequent drug release to occur through diffusion. The aim was to assess the effects of various diluents on the release of the soluble drug, theophylline, from Compritol® 888 ATO matrices produced via direct compression under simulated production conditions using a Stylcam® 100R rotary press simulator. Conclusion: Robust tablets capable of sustaining drug release over 12 h using Compritol® 888 ATO as the lipid matrix were successfully manufactured at conditions analogous to rotary tablet press production. The type of diluent and compaction force used in producing lipid based matrices via direct compression has a significant impact on the drug release profiles obtained.

G. Treanor (1), M. Roberts (1), S. Mostafa (9), C. Miolane (10)



Evaluation of a Rotary Tablet Press Simulator as a Tool for the Characterization of Compaction Properties of Pharmaceutical Products

28th December 2009

Abstract: The Stylcam 100R, a rotary press simulator, was designed to simulate speed profiles of rotary tablet presses. Such a simulator was qualified by numerous laboratories and, actually, its ability to be used for studying the behaviour of powders under pressure should be examined. Then, the purpose of this work was to investigate the performances of the Stylcam 100R for characterizing the compaction behaviour and the tabletting properties of pharmaceutical powders. The compressibility of three pharmaceutical excipients (microcrystalline cellulose, dicalcium phosphate dihydrate and a-lactose monohydrate) was studied. Four compression speeds were used on the compaction simulator. Force–displacement cycles were associated with two energy parameters, the specific total energy (Estot) and the specific expansion energy (Esexp). The mean yield pressure was calculated from Heckel’s plots obtained with the in-die method. The diametral tensile strength of compacts was measured in order to evaluate mechanical properties. To evaluate the accuracy of all these parameters, a comparative study was carried out on an eccentric instrumented press. The values of energy parameters and tensile strengths of tablets are close between the eccentric press and the compaction simulator, whatever the compression speed on the latter. The mean yield pressure values obtained using the two presses are different. Finally, the Stylcam 100R seems to be a good tool for characterising tabletting properties of powders, except for the Heckel’s model probably due to an unadapted equation of deformation and a lack of accuracy of the displacement transducers. Future improvements should allow correcting these two points. 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2874–2885, 2010 Keywords: tablet press simulator; tabletting; excipients; compressibility; compression speed; energy parameters; mean yield pressure; mechanical properties

F. Michaut (11), V. Busignies (11), C. Fouquereau (12) , B. Huet de Barochez (12), B. Leclerc (11), P. Tchoreloff (11)



2012 STYLCAM 200R


2013 On the Links Between Elastic Constants and Effective Elastic Behavior of Pharmaceutical Compacts: Importance of Poisson's Ratio and Use of Bulk Modulus

The elastic properties of pharmaceutical powders and compacts are of great interest to understand the complex phenomena that occur during and after the tableting process. The elastic recovery after compression is known to be linked with adverse phenomena such as capping or delamination of tablets. Classically, the elastic behavior is modeled using linear elasticity and is characterized using only Young's modulus (E), often by using a value extrapolated at zero porosity. In this work, four pharmaceutical products were studied. The elastic behavior of compacts obtained using a large range of applied pressure was characterized. First, it was found more suitable to use apparent elastic moduli than extrapolations at zero porosity. Then, the results indicate that there was not always a good correlation between the values of Young's modulus and the actual elastic recovery of the compacts. Poisson's ratio (v), which differs from one product to another and is porosity-dependent, must be taken into account. Finally, the bulk modulus (K), which combines E and v, was shown to be well correlated with the elastic recovery of the compacts and can be considered as a relevant parameter to characterize the elastic behavior of pharmaceutical compacts. ⃝C 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

Vincent Mazel, Virginie Busignies, Harona Diarra, Pierre Tchoreloff



2013 Image Analysis Quantification of Sticking and Picking Events of Pharmaceutical Powders Compressed on a Rotary Tablet Press Simulator

Purpose The aim of this work was to develop a quantification method based on image analysis, able to characterize sticking during pharmaceutical tableting. Relationship between image analysis features and relevant mechanical parameters recorded on an instrumented tablet press simulator were investigated. Methods Image analysis, based on gray levels co-occurrence matrices (GLCM), generated textural features of the tablet surface. The tableting simulator (Stylcam® 200R, Medelpharm), instrumented with force and displacement transducers, provided accurate records. The tablet defects and compaction process parameters were studied using three pharmaceutical powders (Fast-Flo® lactose, anhydrous Emcompress® and Avicel® PH200 microcrystalline cellulose), five compression pressures (60 to 250 MPa), five lubricating levels, and three types of punches (standard steel, amorphous hard carbon and anti-sticking punches).
Results Texture parameters made it possible to quantify with precision tablets' aspect. The selected parameter IC2 (Informa- tion on Correlation 2) plotted versus the ratio between the ejection shear stress (Esh) and the compression pressure (Cp) let appear a relevant knowledge space where it was possible to identify a normal and a degraded tableting mode. A positive link between those two parameters was shown.
Conclusion Since the Esh/Cp ratio was related to image anal- ysis results, it proved to be an interesting defect tag.

Germinal Mollereau, Vincent Mazel, Virginie Busignies, Pierre Tchoreloff, Fabrice Mouveaux, Philippe Rivière



2013 FEM simulation of the die compaction of pharmaceutical products: Influence of visco-elastic phenomena and comparison with experiments

This work studies the influence of visco-elastic behavior in the finite element method (FEM) modeling of die compaction of pharmaceutical products and how such a visco-elastic behavior may improve the agreement between experimental and simulated compression curves.
The modeling of the process was conducted on a pharmaceutical excipient, microcrystalline cellulose (MCC), by using Drucker–Prager cap model coupled with creep behavior in Abaqus® software. The exper- imental data were obtained on a compaction simulator (STYLCAM 200R). The elastic deformation of the press was determined by performing experimental tests on a calibration disk and was introduced in the simulation. Numerical optimization was performed to characterize creep parameters.
The use of creep behavior in the simulations clearly improved the agreement between the numeri- cal and experimental compression curves (stresses, thickness), mainly during the unloading part of the compaction cycle. For the first time, it was possible to reproduce numerically the fact that the minimum tablet thickness is not obtained at the maximum compression stress.
This study proves that creep behavior must be taken into account when modeling the compaction of pharmaceutical products using FEM methods.

Harona Diarra*, Vincent Mazel, Virginie Busignies, Pierre Tchoreloff



2012 Stylcam 200R Prediction of the compressibility of complex mixtures of pharmaceutical powders

The development of predictive models for the pharmaceutical compaction process is of great interest for not only the formulation step but also in the context of the quality by design development. This paper deals with the prediction of the compressibility, i.e. the prediction of the evolution of the density and the porosity of the compact along with the compaction pressure, both "in-die" (during the compaction) and "out-of-die (after the ejection of the compact). For this purpose, four different mixtures composed of five different pharmaceutical products were studied using a rotative press simulator. The excipients and formulations were chosen to be as near as possible to real industrial formulations. Using the volume as an additive property and a reformulation of the Kawakita equation as a function of the density, it was possible to predict the density of the compact both "in-die" and "outof- die" with a good accuracy (residuals <3.5%). In most of the cases, for the pressure levels used in the pharmaceutical industry, the absolute error on the prediction of the porosity was below 2%. This study demonstrates that this approach could be well suited to predict the compressibility of real pharmaceutical formulations in the industrial context.

V. Busignies*, V. Mazel, H. Diarra, P. Tchoreloff



2012 Stylcam 200R Measurements of Elastic Moduli of Pharmaceutical Compacts: A New Methodology Using Double Compaction on a Compaction Simulator

The elastic properties of pharmaceutical powders play an important role during the compaction process. The elastic behavior can be represented by Young's modulus (E) and Poisson's ratio (v). However, during the compaction, the density of the powder bed changes and the moduli must be determined as a function of the porosity. This study proposes a new methodology to determine E and v as a function of the porosity using double compaction in an instrumented compaction simulator. Precompression is used to form the compact, and the elastic properties are measured during the beginning of the main compaction. By measuring the axial and radial pressure and the powder bed thickness, E and v can be determined as a function of the porosity. Two excipients were studied, microcrystalline cellulose (MCC) and anhydrous calcium phosphate (aCP). The values of E measured are comparable to those obtained using the classical three-point bending test. Poisson's ratio was found to be close to 0.24 for aCP with only small variations with the porosity, and to increase with a decreasing porosity for MCC (0.23–0.38). The classical approximation of a value of 0.3 for ν of pharmaceutical powders should therefore be taken with caution. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2220–2228, 2012

Vincent Mazel, Virginie Busignies, Harona Diarra, Pierre Tchoreloff





Comparing the simulation of a Fette 102i by the STYLCAM 200R March 20th, 2010 – Malta

Summary and Outlook: The Stylcam is a rotary tablet press simulator with just one pair of standard punches. To this end it needs small amounts of powder which is very important in early stages of development. At various velocities, the original force-time profiles of a Fette 102i and the Stylcam simulated ones are quite similar as to the time lag between pre and main compaction, and the curve progression of the main compaction. Also the properties of tablets produced with the Fette 102i and the Stylcam simulating the Fette 102i, are comparable. Achieving high tableting speed like the one prevailing on rotary tablet presses, it is possible to detect capping tendencies at different speeds or speed sensitivity of a formulation in early stages of development. Next step will be to compare the filling construction Fill-O-Matic of the Fette 102i to the different fill shoes of the Stylcam.

K. Duchatsch (4), B. Fretter (4), R.F. Lammens (5), K.J. Steffens (4)



The STYLCAM 200 R, a Rotary Tablet Press Simulator optimising the instrumentation: Correcting for machine deformation upon measuring in-die tablet height April 10th, 2008 – Barcelona

Summary: It is possible to measure the in-die tablet height correctly with the four additional transducers. If the height measurement is not corrected for punch deformation, an error of about 150 μm at 50 kN occurs. By correcting data for the machine deformation the height can be measured with the two pre-mounted transducers but a higher measurement error has to be accepted.

B.Fretter (4)



The Stylcam 200 R, a Rotary Tablet Press Simulator - Optimising the Instrumentation: Characterising the Displacement Measurement System

Conclusion: It is possible to measure the densification part of “force-displacement” curves with sufficient accuracy, because the relation between core position and output signal of the displacement measurement system being used is far more better than their specified precision. Due to the excellent reproducible deviation from linearity, a polynomial regression may be used for discribing this relation. For the examined displacement transducers, it is necessary to prevent the plunger from rotation.

B. Fretter (4), R.F. Lammens (5), K.J. Steffens (4)



Working with Heckel Plots: Method for checking the Plausibility of Force Displacement AAPS Nov 2010, New Orleans

Conclusion: It is possible to obtain exact Heckel Plots with concave punches under conditions close to production (effective dwell time of 7.5 ms).Determining the reference positions for the in-die height measurement with a highly densified tablet seems to be a good method although the precision can be optimised slightly for example by using reference tablets with a smooth surface. To check the plausibility of Heckel data, a set of experiments made at different maximum compaction pressures up to 400 to 600 MPa is strongly recommended. Moreover, the shape of each Heckel curve must be scrutinised. As obvious from the data, Heckel Plots are an error-prone method describing deformation behaviour of powders, due to the difficulties in measuring the in-die tablet height sufficiently accurately. Therefore, it might be difficult to evaluate literature data of Heckel Plots properly. First results show, that internal displacement transducers of the Stylcam mounted outside the tabletting zone can measure the in-die tablet height in good accordance to the external ones. Closer investigations on the comparability of the two systems are on-going. The external measurement configuration described in this paper has the advantage of being able to calculate the deformation from the punch geometry. It can be adapted for most single-punch tablet presses. The internal measurement setup of the Stylcam has the advantage of location and is therefore easy to use.

K. Duchatsch (5), J. Falconet (13), G. Tardy (13), R.F. Lammens (6), B. Fretter (5)



A compaction simulator shared for E-Tabletting, remote tablet formulation STP Pharma Pratiques – September-October 2010

Although its wide use in pharmaceutical industry, powder compression remains complex to handle. It is essential to control a lot of factors and settings to ensure success in its implementation. Nowadays, pharmaceutical labs trend in the use of machines that allow precise process study, in order to develop robust formulations, foresee industrial transfer trouble and reduce a product time-to-market. A state of the art compaction simulator and E-Tabletting concept help industrials study and optimize tablet manufacturing, from drug development to production (reformulation, raw material or rotary tablet press change, etc.) through industrial scale-up. Key words: Tablet – Compression – Simulation – Development – Production – Scale-up – Trouble-shooting.

S. Amoussou-Guenou (14)

1. Liverpool John Moores University, School of Pharmacy and Chemistry, Liverpool, U.K.;

2. Colorcon, Inc., 415 Moyer Boulevard, West Point, PA 19486, USA (www.colorcon.com/about/contact)

3. Janssen Pharmaceutica NV, Beerse, Belgium

4. School of Pharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool , UK

5. Department of Pharmaceutical Technology, University of Bonn, Bonn, Germany

6. TSCL Technical Services Consult Lammens, Leverkusen, Germany

7. Medicines for Children Local Research Network, Alder Hey Children's NHS Foundation Trust, Liverpool, UK

8. Not used

9. Gattefossé (UK) Ltd, Bracknell, UK

10. Gattefossé SA, St Priest, France

11. EA401, Materiaux et Sante, IFR-141, Innovation Therapeutique: du Fondamental au Medicament, Universite Paris Sud-XI, Chatenay-Malabry, France

12. Laboratoires Servier Industrie, Gidy, France

13. MEDELPHARM S.A.S, Bourg en Bresse, France

14. Institut de la Garonne, Estillac, Agen, France