Mean Yield Pressure Research Articles

Compaction behavior and deformation mechanism of directly compressible textured mannitol in a rotary tablet press simulator

Textured mannitol powder is widely used as a pharmaceutical excipient for tablet compaction. In order to choose the right tableting parameters, it is necessary to understand its mechanical behavior during deformation under industrial tableting conditions. The aim of this study was to evaluate the mechanical behavior during deformation of a textured mannitol using a rotary tablet press simulator. Mean yield pressure (Py) obtained by Heckel modeling, Walker coefficients (W) and Stress Rate Sensitivity (SRS) were compared to reference excipients, known for either their plastic (microcrystalline cellulose) or fragmentary (lactose and dibasic calcium phosphate) deformation behavior. Py, W and SRS values showed that the studied textured mannitol has a fragmentary deformation mechanism. Furthermore, this mechanical behavior was not sensitive to lubrication, which is characteristic of fragmentary excipients.

Statistical Quantification of the Impact of Surface Preparation on Yield Point Phenomena in Nickel

Nanoindentation was used to evaluate the effect of three surface preparation techniques—mechanical polishing, electropolishing, and ion polishing—on experimental measurements of incipient plasticity in commercially pure Ni 200. Surface preparation techniques are linked to defect densities, estimated with image quality (IQ) and kernel average misorientation (KAM) data obtained from electron backscatter diffraction patterns and the Taylor relation. Minimum yield pressures are insensitive to surface preparation, while mean yield pressure depends on dislocation density, and the maximum yield pressure is likely influenced by defects other than dislocations. KAM coupled with IQ may be a useful non-destructive parameter to relate surface defect density to the resulting changes in the spatial variability of incipient plasticity during a nanoindentation experiment. This analysis makes the assumption that geometrically necessary dislocation density is proportional to total dislocation density; in cases where this condition is not satisfied, the KAM analysis may not be valid.

COMPRESSIONAL PROPERTIES OF PARACETAMOL TABLET FORMULATIONS CONTAINING MODIFIED STARCH, POLYVINYLPYRROLIDONE AND MAIZE STARCH BP AS BINDERS

The compressional properties of paracetamol tablet formulations containing modified starch (acid hydrolysed), Polyvinylpyrrolidone and maize starch as binders have been investigated. Paracetamol granules obtained by wet massing at varying binder concentrations were compacted using a hydraulic press at different tabletting pressures (28.31-141.56 MNm-2). Density measurements and the compression equations of Heckel and Kawakita were used as assessment parameters where the following variables PY, DA, DB, Do, Pk, and DI were investigated. Formulations containing modified starch showed a slower onset of plastic deformation due to a high mean yield pressure while that of PVP showed the highest onset of plastic deformation. Maize starch BP had the lowest PK value indicating the highest total plastic deformation occurring during compression while modified starch had the highest PK value owing to a lesser total plastic deformation showing that there is a correlation between the compression equations of Heckel and Kawakita as assessment parameters and that modified cassava starch could be useful as a binder in paracetamol tablet formulations to produce tablets with desired compressional properties for particular purposes. Keywords: Modified starch, Polyvinylpyrrolidone(PVP), Heckel equation, Kawakita equation, plastic deformation.

Influence of Some Starch Mucilages on Compression Behaviour and Quality Parameters of Paracetamol Tablets

Aims: To evaluate the effect of mucilages of natural and pregelatinized forms of trifoliate yams, rice and official corn starch binders on a paracetamol tablet formulation. Methodology: Natural starches from two trifoliate yam varieties, and rice were isolated and pregelatinized. Both starch forms were then incorporated into a paracetamol tablet formulation as binders. The influence of the binders on compaction of granules and quality of tablets was assessed. Particle, bulk and tapped densities were measured for all the batches of the prepared paracetamol granules. The Heckel and Kawakita plots from which mean yield pressure, Py and another pressure term Pk, which indicates the pressure required to reduce the volume of the granule bed by 50%, were derived respectively. Both were employed to assess the compaction behaviour of the granules. Quality of the compressed tablets was studied using tensile strength, friability, disintegration time and dissolution properties as evaluation parameters. Results: Pregelatinized starch mucilages generally show lower values of both Py and Pk than natural starch mucilages. Increased concentration of starch mucilage binder also yielded lower values of both Py and Pk. Tablets containing natural starches exhibited higher Tensile strength and lower friability than those formulated with pregelatinized starch binders. Generally, Disintegration time (Dt) and the time taken for 80 % paracetamol to be released (t80) were higher for formulations containing natural starch binders than those containing pregelatinized binders The drug dissolution rate constants k1 and k2, were higher for formulations containing pregelatinized binders. Conclusion: The results obtained are suggestive of the fact that the use of mucilage of pregelatinized starch (rather than natural starch), as well as increase in concentration of the material, would yield formulations with faster onset of plastic deformation as well as higher total plastic deformation. The experimental starches compared well with the standard official corn starch and may thus be developed as substitutes in some tablet formulations.

Influence of Some Starch Mucilages on Compression Behaviour and Quality Parameters of Paracetamol Tablets

Aims: To evaluate the effect of mucilages of natural and pregelatinized forms of trifoliate yams, rice and official corn starch binders on a paracetamol tablet formulation. Methodology: Natural starches from two trifoliate yam varieties, and rice were isolated and pregelatinized. Both starch forms were then incorporated into a paracetamol tablet formulation as binders. The influence of the binders on compaction of granules and quality of tablets was assessed. Particle, bulk and tapped densities were measured for all the batches of the prepared paracetamol granules. The Heckel and Kawakita plots from which mean yield pressure, Py and another pressure term Pk, which indicates the pressure required to reduce the volume of the granule bed by 50%, were derived respectively. Both were employed to assess the compaction behaviour of the granules. Quality of the compressed tablets was studied using tensile strength, friability, disintegration time and dissolution properties as evaluation parameters. Results: Pregelatinized starch mucilages generally show lower values of both Py and Pk than natural starch mucilages. Increased concentration of starch mucilage binder also yielded lower values of both Py and Pk. Tablets containing natural starches exhibited higher Tensile strength and lower friability than those formulated with pregelatinized starch binders. Generally, Disintegration time (Dt) and the time taken for 80 % paracetamol to be released (t80) were higher for formulations containing natural starch binders than those containing pregelatinized binders The drug dissolution rate constants k1 and k2, were higher for formulations containing pregelatinized binders. Conclusion: The results obtained are suggestive of the fact that the use of mucilage of pregelatinized starch (rather than natural starch), as well as increase in concentration of the material, would yield formulations with faster onset of plastic deformation as well as higher total plastic deformation. The experimental starches compared well with the standard official corn starch and may thus be developed as substitutes in some tablet formulations.

Relationship between crystal structure and mechanical properties of ranitidine hydrochloride polymorphs

Polymorphism plays a critical role during pharmaceutical development, as it helps in the selection of optimal solid form. In present study, mechanical properties of ranitidine hydrochloride polymorphs were studied using instrumented tablet press, to understand the effect of crystal packing on the compaction behaviour. Out-of-die compressibility plot and Heckel analysis confirmed greater plastic deformation of form II over form I. Detailed crystallographic examination revealed that form I has several weak C–H⋯O interactions across the ‘proposed slip plane’ parallel to (−2 0 2) that prevent slip under compaction pressure. On the other hand, crystal structure of form II was relatively more open and multiple slip were possible under compaction pressure. These crystallographic features offered increased compressibility and deformability to form II. In absence of an active slip plane system, closed crystal structure of form I resists deformation under compaction pressure and hence showed poor compressibility and higher mean yield pressure. However, form I showed greater tabletability at a given compaction pressure, by virtue of its greater bonding strength.

Influence of Concentration of Modified Maize Starch on Compaction Characteristics and Mechanical Properties of Paracetamol Tablet Formulations

know the influence of the increase on compaction characteristics and the quality of resulting tablets. Three formulations coded B-1, B-2 and B-3 with similar constituents but varying amount of modified Maize starch were designed and prepared by wet granulation process to yield granules that were compacted into tablets. Data and information were collected from out-of-die method; using hand operated tablet press at 5 predetermined pressures and fitted into Heckel plots. Compaction behaviours and mechanical properties of the tablets were evaluated. The three formulations showed consolidation by deformation but at different levels. Sample B-3 which has highest concentration of modified Maize starch seemed to perform on the average better than B-2 and B1. Mean yield pressure vindicated the ease of compression of granules to be B-3 > B-1 > B-2. It is inferred that modified Maize starch could be used to moderate the compaction characteristics of pharmaceutical agglomerates and mechanical properties of resulting tablets. Lower values of yield pressure, constant A, and relative density of B-3 justified the increase in concentration to be beneficial to the formulation. B-3 had highest concentration of modified Maize starch and showed less resistance to consolidation, decrease in granules fragmentation and fast onset of deformation.

Counterintuitive Compaction behavior of Clopidogrel Bisulfate Polymorphs

Being a density violator, clopidogrel bisulfate (CLP) polymorphic system (forms I and II) allows us to study individually the impact of molecular packing (true density) and thermodynamic properties such as heat of fusion on the compaction behavior. These two polymorphs of CLP were investigated for in-die and out-of-die compaction behavior using CTC profile, Heckel, and Walker equations. Compaction studies were performed on a fully instrumented rotary tabletting machine. Detailed examinations of the molecular packing of each form revealed that arrangement of the sulfate anion differs significantly in both crystal forms, thus conferring different compaction behavior to two forms. Close cluster packing of molecules in form I offers a rigid structure, which has poor compressibility and hence resists deformation under compaction pressure. This results into lower densification, higher yield strength, and mean yield pressure, as compared with form II at a given pressure. However, by virtue of higher bonding strength, form I showed superior tabletability, despite its poor compressibility and deformation behavior. Form I, having higher true density and lower heat of fusion showed higher bonding strength. Hence, true density and not heat of fusion can be considered predictor of bonding strength of the pharmaceutical powders.

Functional and tableting properties of acetylated and oxidised finger millet (Eleusine coracana) starch

AbstractThe functional and tableting properties of native (NaFM) and chemically modified (by acetylation, AcFM; and oxidation, OxFM) finger millet starches were investigated. The tablet formation properties of the starches were assessed by Heckel and Kawakita analysis. The swelling power and solubility of the starch increased with increase in temperature with AcFM having the highest swelling power, while OxFM had the highest solubility. X‐ray diffractometry showed that the starches had the characteristic ‘A’ pattern with strong peaks at 3.78, 4.37, 4.87, and 5.17 Å. Chemical modification causes rupture of some starch granules as revealed by the Scanning Electron Micrograph. Chemical modification also leads to improved gelatinisation profile, with reduction in ΔHgel from 9.64 J/g (NaFM) to 3.88 J/g (AcFM) and 8.76 J/g (OxFM). The bulk density and Hausner's ratio increased after chemical modification of the starch. Chemical modification reduced the mean yield pressure, Py (Heckel analysis) but increased the deformability Pk (Kawakita analysis) of the starch compacts. Chemical modification also increased the crushing and tensile strength of the starch compacts, but lowered its disintegration time and friability.

Tableting characteristics of micro-aggregated egg albumin particles containing paracetamol.

The tableting characteristics of micro-aggregated egg albumin particles containing paracetamol were evaluated and compared with non-micro-encapsulated paracetamol and coagulated egg albumin particles. Mean yield pressure values of micro-aggregated egg albumin particles containing paracetamol and coagulated egg albumin particles were 30.5 and 49.3 MPa, respectively, which were lower than the mean yield pressure obtained for paracetamol (97.5 MPa). Paracetamol tablets obtained with micro-aggregated egg albumin particles did not show the capping characteristic of conventional paracetamol tablets. Crushing strength of paracetamol tablets obtained with egg micro-aggegated particles was similar to that obtained using paracetamol granulated with povidone and gelatin as binders at 3 and 6% (w/w) concentrations. Drug release from the paracetamol tablets depends on the choice of excipients. Crospovidone showed good protective characteristics for the tableting of micro-aggregated particles. Crushing strength of paracetamol tablets formed from egg albumin-coated particles could be increased using crospovidone or microcrystalline cellulose as fillers and was decreased by the use of magnesium stearate. Nevertheless, magnesium stearate was useful to decrease the ejection force.

The effect of moisture on the heckel and energy analysis of hydroxypropylmethylcellulose 2208 (HPMC K4M).

The influence of moisture content on the Heckel analysis, energy analysis and strain-rate sensitivity of hydroxyproplymethylcellulose 2208 (HPMC K4M) has been evaluated. An increase in moisture content from 0 to 14.9% w/w decreased the mean yield pressure, probably due to a plasticizing effect of moisture which reduced the resistance of particles to deformation. For each moisture content (0, 2.2, 3.8, 5.9, 9.6 and 14.9% w/w), the initial relative density and the extrapolated density from the linear portion of the Heckel plot, tended to decrease with increasing compression speed. Minor changes were observed in the initial relative density due to changes in the moisture content. The strain-rate sensitivity increased from 21.6 to 50.7% as the moisture content increased from 0 to 14.9% w/w, indicating that the plasticity of HPMC increased with increase in moisture content, whereas increase in moisture content from 0 to 14.9% w/w decreased the plastic energy. Increase in compression force or speed of compaction increased both the plastic and elastic energies. An increase in moisture content from 0 to 5.9% w/w slightly reduced the elastic energy but above 5.9% moisture content the elastic energy was unaffected by the moisture content.

Evaluation of Khaya Gum as a Binder in a Paracetamol Tablet Formulation

A study of the comparative effects of khaya gum and two standard binding agents, polyvinylpyrrolidone (PVP) and gelatin, on the compressional characteristics of a paracetamol tablet formulation and on the mechanical properties of the tablets was made. Compressional characteristics were analysed using density measurements and the Heckel and Kawakita plots. The loose initial relative density (D0) of the formulation increased with increased binder concentration while the packed initial relative density (Di) decreased. The degree of densification achieved for the formulation at low pressures (Db) and at both zero and low pressures (Da) decreased with increased binder concentration. The mean yield pressure (Py) for the formulation decreased with increase in binder concentration, with formulations containing khaya gum having the lowest Py values and those containing gelatin exhibiting the highest values. Another pressure term, Pk (an inverse measure of plasticity) decreased with increase in binder concentration, with formulations containing PVP having the lowest Pk values and those containing khaya gum and gelatin having similar Pk values. The tensile strength (T) of the paracetamol tablets increased with increase in binder concentration while the brittle fracture index (BFI) decreased. Tablets containing PVP exhibited the highest T values while those containing khaya gum exhibited the lowest values. The same trend was obtained for the BFI values with tablets containing khaya gum exhibiting the lowest values. The results suggest that khaya gum could be useful as a binding agent for particular tablet formulations.

Method of modelling the compaction behaviour of cylindrical pharmaceutical tablets

The mechanisms involved for compaction of pharmaceutical powders have become a crucial step in the development cycle for robust tablet design with required properties. Compressibility of pharmaceutical materials is measured by a force–displacement relationship which is commonly analysed using a well known method, the Heckel model. This model requires the true density and compacted powder mass value to determine the powder mean yield pressure. In this paper, we present a technique for shape modelling of pharmaceutical tablets based on the use of partial differential equations (PDEs). This work also presents an extended formulation of the PDE method to a higher dimensional space by increasing the number of parameters responsible for describing the surface in order to generate a solid tablet. Furthermore, the volume and the surface area of the parametric cylindrical tablet have been estimated numerically. Finally, the solution of the axisymmetric boundary value problem for a finite cylinder subject to a uniform axial load has been utilised in order to model the displacement components of a compressed PDE-based representation of a tablet. The Heckel plot obtained from the developed model shows that the model is capable of predicting the compaction behaviour of pharmaceutical materials since it fits the experimental data accurately.

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

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 alpha-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 (Es(tot)) and the specific expansion energy (Es(exp)). 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.

Mechanistic investigation on pressure dependency of Heckel parameter

This work proposed to study the influence of varying compaction pressure on the plastic energy, elasticity (Young's modulus), particle yield strength, strain hardening, and applied pressures on derived Heckel parameter using material with different densification and deformation mechanisms: ibuprofen (IBN), paracetamol (PCM) (elastic behavior), methyl cellulose (Me-Cel), microcrystalline cellulose (MCC), sodium chloride (NaCl) (plastic behavior), and dicalcium phosphate (DCP) (brittle fracture). Force–displacement data were captured during in-die compaction for all materials having different deformation behavior. The apparent mean yield pressure (Py), plastic energy, Young's moduli, strain hardening parameter and rate of increase in Py were calculated from force–displacement compaction profiles obtained across a pressure range of 65–260 MPa. Materials under confined compression loading showed pressure dependent biphasic behavior in Py upon increasing pressure from 65 MPa to 260 MPa. IBN and PCM showed pressure dependency due to simultaneous elasticity and strain hardening upon increasing applied pressure. Me-Cel, MCC, and NaCl showed lower pressure dependency while DCP showed higher change in Py upon increasing pressure as a result of higher yield strength of DCP particles. Apparent mean yield pressure from Heckel analysis was significantly affected by the applied pressure, viscoelastic behavior, particle yield strength, and strain hardening. The simultaneously occurring events of elastic deformation and strain hardening give a false increase in Py at higher applied pressures.

Effect of drug content and agglomerate size on tabletability and drug release characteristics of bromhexine hydrochloridetalc agglomerates prepared by crystallo-co-agglomeration

The objective of the investigation was to study the effect of bromhexine hydrochloride (BXH) content and agglomerate size on mechanical, compressional and drug release properties of agglomerates prepared by crystallo-co-agglomeration (CCA). Studies on optimized batches of agglomerates (BXT1 and BXT2) prepared by CCA have showed adequate sphericity and strength required for efficient tabletting. Trend of strength reduction with a decrease in the size of agglomerates was noted for both batches, irrespective of drug loading. However, an increase in mean yield pressure (14.189 to 19.481) with an increase in size was observed for BXT2 having BXH-talc (1:15.7). Surprisingly, improvement in tensile strength was demonstrated by compacts prepared from BXT2, due to high BXH load, whereas BXT1, having a low amount of BXH (BXH-talc, 1:24), showed low tensile strength. Consequently, increased tensile strength was reflected in extended drug release from BXT2 compacts (Higuchi model, R(2) = 0.9506 to 0.9981). Thus, it can be concluded that interparticulate bridges formed by BXH and agglomerate size affect their mechanical, compressional and drug release properties.

Material properties and compaction characteristics of natural and pregelatinized forms of four starches

Material properties and compaction characteristics of natural and pregelatinized forms of white trifoliate (T.) yam, yellow trifoliate (T.) yam, rice and official corn starches were studied. Physico-chemical properties and viscosity profiles of the starches were evaluated. Pregelatinized starches exhibited lower viscosity values than natural starches in the viscoamylography. The pregelatinized starches showed more densification than natural starches during compression and also had lower mean yield pressure, P y. The ranking of P y for the starches was; corn < white T. yam < yellow T. yam < rice. The values of P k, an inverse measure of plasticity, were, however, lower for the natural starches with the ranking for the starches being white T. yam < yellow T. yam < corn < rice. Tablets produced from pregelatinized starches had lower values of tensile strength (T) and brittleness (BFI) than those made from natural starches. The ranking of T for the starches was generally white T. yam > corn > yellow T. yam > rice. The rankings of the BFI for the natural and pregelatinized starches were corn < yellow T. yam < white T. yam < rice; and corn < white T. yam < yellow T. yam < rice, respectively. The material properties of the starches appear to show some limited correlation with their tablet properties. The experimental starches showed similar properties to official corn starch in many cases and could serve as suitable alternatives for particular purposes.

The influence of molecular properties on the mean yield pressure of drugs - are issues of compressibility predictable based on chemical structure?

This article aims to predict the mean yield pressure during tableting using solely the chemical structure. Diverse chemical predictors were calculated using molecular modeling tools and the mean yield pressure was estimated by a partial least square analysis. The model revealed the relevant parameters for plastic deformation during tableting. Accordingly, the number of torsional bonds, molar volume, molecular weight, melting point, and cohesive energy had greatest impact on the mean yield pressure. The response surface plots of these predictors indicated that mainly drugs of lower molecular weight ( 200 °C), and having a low number of torsional bonds (

Evaluation of the mechanical properties of extrusion-spheronized beads and multiparticulate systems

Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate systems has not been adequately studied. Aim: The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads. Method: Heckel analysis (mean yield pressure, Py), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a PressterTM linear rotary tablet machine simulator operating at several combinations of speed and force. Results: The GMS-placebo beads exhibited the lowest Py values (9.1 ± 1.6 MPa) and TWC (1.9 ± 0.3 J) overall and these values steadily increased with increases in both applied speed and force. Although the placebo beads had the lowest ER values of 3.8 ± 0.7%, these beads showed significant time-dependent deformation behavior based on their SRS value of 70.2%. Heckel analysis showed that uncoated theophylline beads containing 58% ethylcellulose were more compressible than control beads containing 58% dicalcium phosphate dihydrate, the latter having the highest overall Py of 79.3 ± 3.8 MPa for the low speed/low force condition. Heckel plots also showed that 50:50 ratios of blends containing drug beads coated with either Surelease® or Eudragit® NE30D behaved similarly under increasing force and speed. Surelease®-coated cimetidine beads gave the highest Py, TWC, and ER values and these values were higher than Eudragit® NE30D-coated beads. The 50:50 blend ratios containing coated cimetidine beads showed higher Py, TWC, and ER values than the 60:40 ratios. Conclusion: Variation in the compressibility of different beads and blends can be attributed to excipients used in their formulation as well as to the drug bead-to-placebo bead ratio.

Selected Physical and Chemical Properties of Feverfew (Tanacetum parthenium) Extracts Important for Formulated Product Quality and Performance

The objectives of this research are: (1) to assess selected formulation-relevant physical properties of several commercial Feverfew extracts, including flowability, hygroscopicity, compressibility and compactibility (2) to develop and validate a suitable extraction method and HPLC assay, and (3) to determine the parthenolide content of several commercial Feverfew extracts. Carr's index, minimum orifice diameter and particle-particle interaction were used to evaluate powder flowability. Hygroscopicity was evaluated by determining the equilibrium moisture content (EMC) after storage at various % relative humidities. Heckle analysis and compression pressure-radial tensile strength relationship were used to represent compression and compaction properties of feverfew extracts. An adapted analytical method was developed based on literature methods and then validated for the determination of parthenolide in feverfew. The commercial extracts tested exhibited poor to very poor flowability. The comparatively low mean yield pressure suggested that feverfew extracts deformed mainly plastically. Hygroscopicity and compactibility varied greatly with source. No commercial feverfew extracts tested contained the label claimed parthenolide. Even different batches from the same manufacturer showed significantly different parthenolide content. Therefore, extract manufactures should commit to proper quality control procedures that ensure accurate label claims, and supplement manufacturers should take into account possible differences in physico-chemical properties when using extracts from multiple suppliers.