APPLICATION OF COMPACTION EQUATIONS FOR POWDERED PHARMACEUTICAL MATERIALS

Transcription

1 APPLICATION OF COMPACTION EQUATIONS FOR POWDERED PHARMACEUTICAL MATERIALS Maroš ECKERT, Peter PECIAR, Alexander KROK,2, Roman FEKETE Institute of Process Engineering, Faculty of Mechanical Engineering, Slovak University of Technology in Bratislava, Námestie Slobody 7, 82 3, Bratislava, Slovakia. Slovakia. 2 Department of Chemical and Process Engineering, Faculty of Engineering and Physical Sciences, University of Surrey, Guidford, GU2 7XH, United Kingdom. a.krok@surrey.ac.uk Keywords: powder compaction, Heckel, Kawakita, Cooper-Eaton Abstract The paper is focused on an analysis of the most frequently used compaction s for powdered materials such as Heckel, Kawakita and Cooper-Eaton. Compacting powdered materials is accompanied by various mechanisms of densification dependent on the properties of the compressed material, which makes the more satisfactory for a certain group of materials and for another groups less so, or makes the completely unsuitable. To determine the suitability of the experimental measurements have to be implemented on an instrumented laboratory press. Then these obtained data are approximated by the specific compaction and use the regression analysis to determine the parameters describing the required material or physical properties of the compressed material. INTRODUCTION Compaction is one of the most common methods of processing powdered materials in industries such as powder metallurgy, powder ceramics or in the production of pharmaceutical drugs. Currently in the pharmaceutical industry die compaction has an irreplaceable role and drugs in a tablet form represent 90 % of the total production of drugs. Therefore, it is necessary to know the behavior of a powder during the die compaction process and to be able to qualitatively and quantitatively describe the process using parameters characterizing some specific material property. Then the data can be compared and so also qualify a powder material, determine the suitability of the material for such treatment or the possibility of improving its features. 2 ANALYSIS OF COMPACTION EQUATIONS Compacting powders into a tablet form is a process of reducing porosity and of forming materials into a solid compact. The structure of powders changes during compression and densification takes place mainly due to the rearrangements of particles, their fragmentation and plastic deformation. The compression of powdered into a tablet form is a complex and irreversible dynamic process. Several relationships between stress-strain, pressure-volume, pressure-porosity or pressure-density have been proposed to define the compaction behavior of powders, since natural strain is proportional to changes in powder-bed height or volume under applied pressure.

2 Compaction s put into relation the state of compaction parameters such as porosity, volume or density with respect to the applied pressure. In the interpretation of the data of compaction it is important to know what compaction mechanisms operate at different levels of pressure. 2. HECKEL EQUATION Heckel [,3] is one of the most common s describing the mechanism of reducing volume during compaction. It is based on the assumption that powder compression follows first-order kinetics with the interparticulate voids as the reactant and the densification of the powder as the product. Then the degree of compaction with increasing compressing pressure is proportional to the porosity thusly: ρ =ε, () where ρ is relative density at applied pressure and ε is porosity. Relative density is defined as the ratio between the density of the compact at pressure and the true density of the solid particles. Porosity is given by: ε = = ρ, (2) then the () can by expressed as: ρ = ρ, (3) and by solving the differential (3): ln ρ =+, (4) Plotting the value of ln/ ρ against applied pressure leads to the plot with a linear section with a slope and intercept. The reciprocal of the parameter expresses the constant dependent on the material known as yield pressure, which is inversely related to the ability of the material to deform plastically under pressure. Thus, the lower values indicate the onset of plastic deformation at lower pressures. Intercept expresses the parameter dependent on the original compact volume during die filling and the initial particle rearrangement. The Heckel plot has three stages of densification. 2.2 KAWAKITA EQUATION Kawakita [,3] was developed to study powder densification using the degree of reduction in volume expressed as: = =, (5) (5) can be rearranged to give: = +, (6)

3 where is the initial volume of the powder and is the volume of the powder at pressure. Constants and are obtained from the slope and intercept of the / versus plot. The constant expresses the minimum porosity of the powder before compressing and the value of indicates initial relative density ρ. The constant, also known as the coefficient of compression, is related to the plastic material properties. Its reciprocal expresses the pressure parameter, which is the pressure required to reduce the volume of the powder by 50 %. For plastic materials, the value of is inversely proportional to the degree of the plastic deformation during the compaction process, therefore lower values of indicate a higher degree of plastic deformation. 2.3 COOPER-EATON EQUATION Cooper-Eaton [3] assumes that the compression of powders follows a two-step process. The first step is the rearrangement of particles so that the particles fill those voids that are larger than or of the same size as that of the particles. In the second stage there occurs deformation (elastic, plastic, fragmentation), whereby the voids that are smaller than that of the particles are filled due to applied pressure. Cooper-Eaton is expressed in the form: ρ ρ = exp + exp, (7) ρ where ρ is the initial relative density of the powder, ρ is the relative density at pressure, constants, indicate the proportion of the total compaction achieved by filling those voids larger or of the same size ( ) and smaller ( ) than the actual particles. Constants and describe the pressures at which this two-stage densification is thought to occur. Graphical evaluation is the relationship between applied pressure and fractional volume compression, which is expressed by the left side of the (7). All of the constants can be determined by a nonlinear plot. 3 EXPERIMENTAL MEASUREMENTS 3. EXPERIMENTAL STATION The measurement is performed on a KISTLER electromechanical press (Figure a). The press contains a force sensor and a sensor of punch position. The maximum press force is 60 kn and the range of displacement of the punch is 200 mm. Compression of the powder was carried out in a die tools (Figure b). It consists of a steel die and a punch with a diameter of 20 mm. 3.2 EXPERIMENTAL MATERIAL The material used in the measurements was Avicel PH 02. This material belongs among the oldest type of microcrystaline cellulose (MCC) and is one of the most widely used pharmaceutical excipients. The cellulose is used in powdered and also in microcrystalline form. Its properties make it ideal for formulating dosage forms with controlled release of the drug to assure a prolonged, delayed or pulsed effect of the drug substance in a living organism.

4 a) b) Figure : a) KISTLER Electomechanical press, b) Tabletting die - compressing punch, 2 - die, 3 - compressing powder, 4 - base of the die tools 3.3 RESULTS OF EXPERIMENTAL MEASUREMENTS Experimental measurements were carried out at a constant compression speed of 00 mm/s and the pressing force was 50 kn which, after calculation with respect to the surface of the compressing punch, represent a pressure of 59,6. Parameters of compaction such as relative density and powder volume were determined by the measured values of the punch position. Consequently, plots of each compaction were made and the parameters of the s were determined by regression analysis. Regresion Heckel Slope =+ ln ρ =+ = 0,0277 Parameter = 78,3 Intercept = 0,4822 Coefficient of deter. 0,99856 Figure 2: Heckel plot of the MCC Avicel PH 02 Table : Parameters of the linear regression of Heckel

5 Regresion Kawakita =+ = + Slope =,2904 Figure 3: Kawakita plot of the MCC Avicel PH 02 Parameter 0,775 Parameter ρ = 0,225 Intercept = 6,334 0,0789 Constant Parameter = 2,67 Coefficient of deter. 0,99983 Table 2: Parameters of the linear regression of Kawakita Regresion = exp + exp + Cooper-Eaton ρ ρ = exp + exp ρ Parameter = 0,38864 Figure 4: Cooper-Eaton plot of the MCC Avicel PH 02 Parameter = 0,58875 Parameter = 2,09623 Parameter = 7,487 Coefficient of deter. 0,99865 Table 3: Parameters of the non-linear regression of Cooper-Eaton

6 4 CONCLUSION It can be concluded on the basis of graphical evaluation that all the compaction s are suitable for describing the process of compressing powdered material on the MCC Avicel PH 02. In the case of the Heckel and Kawakita plots, there is a significant linear correlation describing the main mechanism of the compaction through plastic deformation of the powder particles. Heckel plot shows that the curve begins to adopt a tendency corresponding to the elastic deformation of the solid compact and therefore further compression does not affect the plastic deformation of the particles and also does not affect the formation of new bonds between the particles. Kawakita with a very good accuracy gives the initial relative density ρ and indicates that a volume reduction of 50 % was achieved at a relatively low compression pressure, which is primary caused by rearrangement and by filling the voids of the particles. A more detailed description of the mechanisms of densification is provided by the Cooper-Eaton plot. It reflects that plastic deformation occurring at low applied pressures had a greater impact on the overall compaction. Fragmentation occurred to a very small degree, because Avicel contains elastic particles and thus there was no overlapping of the three mechanisms of compaction, which caused a significant transition between these mechanisms. ACKNOWLEDGMENTS This article was created with the support of the Ministry of Education, Science, Research and Sport of the Slovak Republic within the Research and Development Operational Programme for the project "University Science Park of STU Bratislava", ITMS , co-funded by the European Regional Development Fund. This article was created within the grant project "Analysis of the thermo-mechanical properties of powder material during uniaxial compression in the pharmaceutical industry" within The program of support for excellent teams of young researchers at the Slovak University of Technology. REFERENCES [] DENNY, P.J Compaction s: A comparison of the Heckel and Kawakita s. In Powder Technology. 2002, vol. 27, pp [2] ODEKU, O.A The compaction of pharmaceutical powders [review]. Available: powders/ [3] SONNERGAARD, J.M Impact of particle density and initial volume on mathematical compression models. In European Journal of Pharmaceutical Sciences. 2000, vol., pp [4] WU, C.Y., et. al Modeling the mechanical behavior of pharmaceutical powders during compaction. In Powder technology. 2005, vol. 52, pp. 07. [5] CHEN, W. - MALGHAN, S.G Investigation of compaction s for powders. In Powder Technology. 994, vol. 8, pp