Use of 3-D modelling in early development phase of pectin tablets

This study examines the contribution of a 3-D model in an early development of pectin tablets. The aim of this work was to extract as much information of the compression behavior from as few tablets as possible. Pectins with various degrees of methoxylation (DM) were studied (4%-72%). The compressibility was evaluated using classic “in-die” Heckel and Kawakita analyses in addition to the 3-D modeling. For validation purposes well-known reference materials were included. 3-D modeling applied to data of single tablets yielded some information on their compressibility. When several tablets with different maximum relative densities (rel, max) were included, no additional information was obtained through classic evaluation. However, the 3-D model provided additional information through the shape of the 3-D parameter plot. Pectins with a DM $ 25% consolidated predominantly by elastic deformation similarly to the 3-D parameter plot of pregelatinized starch (PGS). The 3-D analysis also suggests some degree of fragmentation and, for some of the low-methoxylated pectins (DM # 10%), viscoelastic deformation. This study showed that by applying 3-D modeling it is possible to differentiate between elastic and viscoelastic materials for tablets with different  rel, max values.

[1]  Kimio Kawakita,et al.  Some considerations on powder compression equations , 1971 .

[2]  J. Nordström,et al.  A statistical approach to evaluate the potential use of compression parameters for classification of pharmaceutical powder materials. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[3]  J. Nordström,et al.  A particle rearrangement index based on the Kawakita powder compression equation. , 2009, Journal of pharmaceutical sciences.

[4]  J. Sonnergaard Impact of particle density and initial volume on mathematical compression models. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  A. Bauer-Brandl,et al.  On the physical interpretation of the initial bending of a Shapiro-Konopicky-Heckel compression profile. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  P. Sriamornsak,et al.  Studies on pectins as potential hydrogel matrices for controlled-release drug delivery. , 1999, Drug development and industrial pharmacy.

[7]  C. Nyström,et al.  Studies on direct compression of tablets XVII. Porosity—pressure curves for the characterization of volume reduction mechanisms in powder compression , 1986 .

[8]  Sarsvatkumar Patel,et al.  Effect of Particle Size and Compression Force on Compaction Behavior and Derived Mathematical Parameters of Compressibility , 2006, Pharmaceutical Research.

[9]  K. Picker-Freyer,et al.  Tableting and tablet properties of alginates: characterisation and potential for Soft Tableting. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[10]  K. Picker,et al.  True density of swellable substances at different relative humidities : a new approach to its determination , 1996 .

[11]  Katharina M. Picker-Freyer,et al.  The 3‐D model: Experimental testing of the parameters d, e, and ω and validation of the analysis , 2007 .

[12]  Ingunn Tho,et al.  Application of multivariate methods to compression behavior evaluation of directly compressible materials. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  M. H. Rubinstein,et al.  A comparative investigation of compression simulators , 1989 .

[14]  Katharina M. Picker,et al.  The 3-D model: Comparison of parameters obtained from and by simulating different tableting machines , 2008, AAPS PharmSciTech.

[15]  K. Picker-Freyer,et al.  Evaluation of powder and tableting properties of chitosan , 2006, AAPS PharmSciTech.

[16]  G. Alderborn,et al.  Analysis of the Compression Mechanics of Pharmaceutical Agglomerates of Different Porosity and Composition Using the Adams and Kawakita Equations , 2000, Pharmaceutical Research.

[17]  S. A. Sande Pectin-based oral drug delivery to the colon , 2005, Expert opinion on drug delivery.

[18]  P. Paronen Heckel Plots as Indicators of Elastic Properties of Pharmaceuticals , 1986 .

[19]  G. Bolhuis,et al.  Studies on tableting properties of lactose , 1985, Pharmaceutisch Weekblad.

[20]  Aditya Mohan Kaushal,et al.  Mechanistic investigation on pressure dependency of Heckel parameter. , 2010, International journal of pharmaceutics.

[21]  C. Lerk CONSOLIDATION AND COMPACTION OF LACTOSE , 1993 .

[22]  J. Rokem,et al.  In Vitro Evaluation of Calcium Pectinate: A Potential Colon-Specific Drug Delivery Carrier , 1993, Pharmaceutical Research.

[23]  R C Rowe,et al.  The effect of punch velocity on the compaction of a variety of materials , 1985, The Journal of pharmacy and pharmacology.

[24]  Ingunn Tho,et al.  Multivariate analysis of relationships between material properties, process parameters and tablet tensile strength for alpha-lactose monohydrates. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[25]  Ingunn Tho,et al.  Comparative evaluation of the powder and compression properties of various grades and brands of microcrystalline cellulose by multivariate methods , 2009, Pharmaceutical development and technology.

[26]  K. Picker-Freyer,et al.  Material and tablet properties of pregelatinized (thermally modified) Dioscorea starches. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[27]  A. McKenna,et al.  Effect of particle size on the compaction mechanism and tensile strength of tablets , 1982, The Journal of pharmacy and pharmacology.

[28]  J. Sonnergaard,et al.  A critical evaluation of the Heckel equation. , 1999, International journal of pharmaceutics.

[29]  A. Bauer-Brandl,et al.  Direct Compression Behavior of Low- and High-Methoxylated Pectins , 2009, AAPS PharmSciTech.

[30]  R. Rowe,et al.  The effect of the relationship between punch velocity and particle size on the compaction behaviour of materials with varying deformation mechanisms , 1986, The Journal of pharmacy and pharmacology.

[31]  L L Augsburger,et al.  Plastic flow during compression of directly compressible fillers and its effect on tablet strength. , 1977, Journal of pharmaceutical sciences.

[32]  A. Bauer-Brandl,et al.  Effect of degree of methoxylation and particle size on compression properties and compactibility of pectin powders , 2012, Pharmaceutical development and technology.

[33]  J. Nunthanid,et al.  Swelling and erosion of pectin matrix tablets and their impact on drug release behavior. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[34]  Katharina M. Picker,et al.  “Soft Tableting”: A New Concept to Tablet Pressure Sensitive Materials , 2004, Pharmaceutical development and technology.

[35]  Katharina M. Picker,et al.  The 3D Model: Explaining Densification and Deformation Mechanisms by Using 3D Parameter Plots , 2004, Drug development and industrial pharmacy.

[36]  K M Picker,et al.  A new theoretical model to characterize the densification behavior of tableting materials. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[37]  D. Attwood,et al.  Studies on pectin formulations for colonic drug delivery , 1994 .

[38]  Changquan Calvin Sun,et al.  Influence of Elastic Deformation of Particles on Heckel Analysis , 2001, Pharmaceutical development and technology.

[39]  G. Bonacucina,et al.  Differences between eccentric and rotary tablet machines in the evaluation of powder densification behaviour. , 2005, International journal of pharmaceutics.

[40]  Ichiro Hattori,et al.  Characteristic Constants in Kawakita's Powder Compression Equation , 1974 .