Heckel Equation Research Articles

Preparation and standardization of a herbal agent for the therapeutic management of asthma

This study aims to develop a suitable single tablet dosage form containing a mixture of hot water stem back extracts of Anogeissus leiocarpus and Prosopis africana (AA1), suitable for use in the therapeutic management of asthma. The compaction characteristics of the oven-dried hot water extract (HWE) were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AA1 exhibited high densification due to dye filling while the subsequent rearrangement of the granules did not contribute, significantly, to their densification. The granules had enhanced plasticity as shown by the low yield point, Py. The tablets produced from the extract had good mechanical properties, with hardness increasing with compression pressure while the friability decreased. Of the four disintegrants tested, tablets containing Explotab had the shortest disintegration time of 11 min while tablets containing Prosolv had the longest disintegration time of 40 min. The order of disintegrant property is Explotab > Cellactose > Emcocel > Maize starch > Prosolv. Dissolution results (t90%) show that tablets containing Explotab released 100% of the drug in 20 min proving to be the most suitable in acute asthma attack. The order of dissolution is Explotab > Cellactose > Maize starch > Prosolv > Emcocel. It is concluded that incorporation of Explotab (10%w/w) as a disintegrant in AA1 preparation produced tablets of suitable compressional properties and ensured adequate drug release for the management of acute asthma.

Compaction studies of alternate solid forms of celecoxib

The aim of this study was to compare the compaction behavior of crystalline celecoxib (CryCEL), amorphous celecoxib (AmCEL) and celecoxib (CEL) – polyvinyl pyrolidone (PVP) – meglumine (MEG) solid dispersion (Ter-Mix) using texture analyzer and hydraulic press for low and high pressures, respectively. Pressure induced devitrification in the amorphous and ternary system was also studied using PXRD. Elastic energy/plastic energy (EE/PE) ratio of AmCEL, CryCEL and Ter-Mix was found to be 1.71, 2.32, and 1.91, respectively at 6.35 MPa. Similar trend was observed at all studied compaction pressures. AmCEL showed significant devitrification, while Ter-Mix showed degree of crystallinity (DOC) of 11.9%, when compacted at tableting pressures of 109 MPa. Parameters ‘ a’, ‘1/ b’, and ‘Py’ obtained using Kawakita equation and Heckel equation gave values of 0.86, 5.2, and 253.4 MPa for CryCEL, 0.89, 4.85, and 103 MPa for AmCEL and 0.68, 16.1, and 169.6 MPa for Ter-Mix, respectively. The study revealed significant differences in compaction properties of CryCEL, AmCEL, and Ter-Mix. AmCEL was not suitable for compacted solid dosage forms due to pressure induced devitrification. However, stabilized AmCEL in Ter-Mix showed relatively lesser devitrification and can be developed as compacted dosage forms.

Evaluation of the material and tablet formation properties of modified forms of Dioscorea starches

Starches obtained from four different Dioscorea species—namely, White yam (Dioscorea rotundata), Bitter yam (Dioscorea dumetorum), Chinese yam (Dioscorea oppositifolia), and Water yam (Dioscorea alata)—were modified by cross-linking, hydroxypropylation, and dual modification—cross-linking followed by hydroxypropylation. The physicochemical, material, and tablet properties of the modified starches were investigated with the aim of understanding their properties to determine their potential use for different applications. The tablet formation properties were assessed using 3D modeling, the Heckel equation, and force-displacement profiles. The analyzed tablet properties were elastic recovery, compactibility, and disintegration. The result indicates that the modifications generally increased the swelling power for all the starches in the rank order hydroxypropyl > hydroxypropylated cross-linked > cross-linked (CL) while the solubility did not show a clear-cut pattern. This indicates that hydroxypropylation generally showed the strongest effects on swelling. Furthermore, hydroxypropylation improved the hot water swelling of the CL starches. The modifications did not cause any detectable morphological change in the starch granules shape or size although slight rupture was observed in some granules. CL starch had the lowest water sorption capacity and hydroxypropylation increased the sorption capacity of the CL starches. The material property results indicate that hydroxypropylation and cross-linking did not significantly improve the flowability and compressibility but improved bonding, which resulted in an increased compaction and higher tablet crushing force even though they all disintegrated rapidly. Thus, the modified Dioscorea starches showed potentials for development as new excipients in solid dosage form design, and they could be useful as disintegrants or for Soft tableting.

Multivariate analysis of relationships between material properties, process parameters and tablet tensile strength for α-lactose monohydrates

The present work describes an approach to quantify relationships between the material properties of various α-lactose monohydrate grades (αLM), process parameters (punch velocity, lubricant fraction) and the tablet tensile strength (TS). Milled, sieved, agglomerated and spray-dried αLMs were studied. Each material was tableted (11 mm flat punches, constant true volume of 0.2833 cm 3) on a compaction simulator at a pressure of 104.4 ± 0.1 MPa. The force–displacement data was analyzed by applying a combination of compression descriptors (derived from Kawakita and Heckel equations, work-related parameters). The relationships were evaluated and quantified by principal component analysis (PCA) and partial least square regression (PLS-1). PCA verified fundamental relationships between different powder and compression properties of studied materials. It was found that the compression descriptors Kawakita ‘1/ b’ and WoC were sufficient to distinguish the tested αLM-grades, even in combination with different lubricant fraction or by utilizing different punch velocities; the identified descriptors correlated with TS. These relationships were quantified by PLS-1. Finally, TS were successfully predicted for all αLM with the help of separate optimized PLS-1 models. The present study shows an approach how to extract relevant information about tableting behavior from a limited amount of material.

Compaction Behavior and Mechanical Properties of Uniaxially Pressed Bi-W Composites

Powder metallurgy is a useful route to forming particulate composite materials; however, the densification of hard and soft powder mixtures is usually inhibited by the more refractory phase. The Bi-W powder compacts were uniaxially pressed at room temperature and the compaction behavior and mechanical properties were evaluated. Pressing was performed in incremental steps from ~1 to 540 MPa. After each step, the pressure was relieved and the thickness and sound-wave transit time were measured in situ (in the die), in order to determine the density and sound-wave velocity in the compact. The data show that the unreinforced Bi powder compacts to ~98 pct density at 540 MPa. The W reinforcement inhibits the densification process, resulting in increased levels of residual porosity. The compaction behavior was evaluated using a modified Heckel equation, while the porosity dependence of the ultrasonically determined elastic modulus was described by a site percolation approach. Postcompaction sound-wave velocity and Vicker’s hardness measurements show <5 pct anisotropy between the axial (pressing) and radial directions. The mechanical characterization illustrates the competing effects of the W reinforcement and the associated residual porosity.

Synthesis and characterization of new copolymers of ethyl methacrylate grafted on tapioca starch as novel excipients for direct compression matrix tablets

In last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluates the physicochemical and mechanical properties of new graft copolymers of ethyl methacrylate (EMA) on tapioca starch (TS) and hydroxypropylstarch (THS), synthesized by free radical polymerization and dried in a vacuum oven (OD) or freeze–dried (FD). Infrared and 13C NMR spectroscopies confirm the change of chemical structure of the copolymers and X-ray diffraction shows up the higher amorphization of copolymers respect to the carbohydrates. Particle size analysis and SEM indicate that graft copolymerization leads to an increase of particle size and a more irregular shape. Graft copolymerization implies decrease of density and moisture content values. Heckel equation shows that copolymers have less densification by particle rearrangement and fragmentation than carbohydrates. Concerning the drying methods, FD products have larger plasticity and lower elasticity than OD copolymers. Graft copolymerization produces a decrease of the applied pressure necessary to obtain tablets, ejection force and friction work. Furthermore, graft copolymers show longer disintegration time than tablets from raw starches. These qualities suggest that these copolymers could be used as excipients in matrix tablets obtained by direct compression, and with a potential use in controlled release.

Application of multivariate methods to compression behavior evaluation of directly compressible materials

The present study is an approach to describe and predict compaction and tablet properties by a combination of a set of commonly used mathematical descriptors and multivariate methods based on continuous compression profiles. Effects of formulation and process parameters (e.g. composition, powder properties, compression speed) of well-known direct compression excipients of widely plastic, elastic, and fragmentary properties, and binary mixtures thereof were characterized. 2 3-Full factorial designs with three centre points were applied for Avicel ® PH 102, Starch 1500 ® and Spherolac ® 100. Tablets (11 mm diameter) were compressed from hand-weighed powder (of constant true volume) at 104.1 ± 0.2 MPa using a compaction simulator, yielding highly repeatable data. Heckel equation and work-related parameters were derived. Data were evaluated by multivariate analysis (principal component analysis (PCA) and partial least squares (PLS-2, PLS-1) models). The PCA indicated that Hausner ratio, work of compression (WoC), and tensile strength (TS) are negatively correlated to yield pressure of plastic (YPpl) and elastic deformation (YPel), Emcompress ® fraction, helium-, bulk-, and tapped density, and particle size. PLS-2 model correlated all design variables, their interaction and square effects with all response variables. These correlations were further quantified for the most important responses (e.g. WoC, TS, YPpl, and YPel) by optimizing separate PLS-1 models. The results were found in accordance with expectations and show the ability of this approach to quantify compression behavior, as a step towards a ‘formulation development tool’ for tablets.

A Systematic Study on Flowability and Compressibility of Asparagus racemosus root Powder for Tablet Preparation

The dried root of Asparagus racemosus is widely used as mild antihypertensive and tranquilizer. The objective of the present research was to study the original flowability, compressibility and compactibility of Asparagus racemosus root powder and develop its tablet formulations by wet granulation and direct compression technology. The consolidation behavior of drug and tablet formulations were studied by using Heckel and Leuenberger equation. Asparagus racemosus root powder showed very poor flowability and compactibility. Kawakita analysis revealed improved flowability for formulations prepared by direct compression and wet granulation technique. The Heckel plot showed that Asparagus racemosus powder is soft in nature and poor in die filling. Granules showed higher degree of plasticity and fragmentation than powder and direct compression formulations. The compression susceptibility parameter for compact formed by direct compression and wet granulation technique indicated that the maximum crushing strength is reached faster at lower pressures of compression as opposed to Asparagus racemosus powder. From this study, it is concluded that desired flowability, compressibility and compactibility of Asparagus racemosus root powder can be obtained by direct compression and wet granulation technique

Material and tablet properties of pregelatinized (thermally modified) Dioscorea starches

The material and tablet formation properties of pregelatinized (thermally modified) forms of four Dioscorea starches have been investigated. Dioscorea starches were pregelatinized followed by either oven drying (PS) or freeze drying (FD) and used as excipient in direct compression. The physicochemical, morphological and material properties of the pregelatinized starches have been investigated. The tablet formation properties were assessed using the 3-D modeling parameters, the Heckel equation and the force–displacement profiles. The tablet properties were evaluated using the elastic recovery, compactibility plots and the disintegration test. The results indicate that pregelatinization improved the compressibility and flowability of the Dioscorea starches. The high bulk and tap densities of PS coupled with their good flowability offer a unique possibility of the starches being used as filler in capsule formulations. The modified starches generally showed differences in their time and pressure dependent deformation behaviour. PS exhibited higher elasticity during tableting. FD Chinese and FD Bitter showed higher plasticity and low fast elastic deformation than the PS forms of the starches indicating that the FD starches undergo the highest plastic deformation. However, FD starches generally showed higher compactibility compared to the PS forms of the Dioscorea starches. While FD White and FD Water showed fast disintegration time and high compactibility, FD Chinese and FD Bitter were non-disintegrating and showed high compactibility. The high compactibility observed with the FD starches appears to be as a result of material change occurring during tableting probably due to the effect of temperature or pressure or a combination of both factors. Thus, FD White and FD Water starches could be useful when high crushing force and fast disintegration are of concern while FD Chinese and FD Bitter, which were non-disintegrating, could find application as excipients for controlled drug delivery.

Studies on the reduction of tensile strength of tablets after roll compaction/dry granulation

Roll compaction/dry granulation is a widely used technique for granulation. A major drawback is the reduction of tablet tensile strength compared to other granulation methods. The purpose of this study was to determine the reasons for the partial loss in compactibility. Microcrystalline cellulose of different particle sizes was roll-compacted/dry-granulated. The granules were sieved to obtain two sieve cuts and then compressed into tablets. The particle-size distribution within the sieve cut was determined using image analysis. The specific surface area of sieve cut was obtained by nitrogen adsorption. Heckel equation was used to determine the change in compressibility. The work-hardening phenomenon was found to be caused by a combination of particle-size enlargement and hardening of material. Although particle size of granules was equal, the use of smaller particles as raw material resulted in tablets with higher tensile strength due to higher specific surface area. Both work-hardening and particle-size enlargement cause the partial loss in compactibility. The reduction in tensile strength could be compensated by producing smaller granules or using raw materials with small particle sizes.

Effect of Grewia gum on the mechanical properties of paracetamol tablet formulations

Grewia gum has been evaluated as a binder in paracetamol tablet formulations. Compressional properties of the formulations were analyzed using density measurements and the compression equations of Heckel and Kawakita as assessment parameters. Formulations containing Grewia gum as a binder show a slower onset and lower amount of plastic deformation than those containing PVP. The Db values for formulations containing Grewia gum, increased with increased concentration up to 4% w/w. Formulations containing Grewia gum were also found to exhibit higher degree of packing than those containing PVP. Yield values for formulations containing Grewia gum was found to be at variance with the binder concentration. The values increased between 1 and 2% w/w and decreased between 2 and 4% w/w. A linear relationship was found to exist between N/C and N for formulations containing Grewia gum at all concentrations. Grewia gum was found to improve the fluidity of paracetamol granulation better than PVP. This study suggests that Grewia gum compares favorably with the standard binder PVP used hence could be a useful substitute binder in paracetamol tablet formulations. Key words: Grewia gum, PVP, paracetamol, Heckel equation, Kawakita equation, compaction characteristics.

Study of the densification of a nanostructured composite powder: Part 1: Effect of compaction pressure and reinforcement addition

The compressibility behavior of Al-AlN nanostructured composite powder with different amount of reinforcement content was studied. The composite powder was synthesized by blending and high-energy milling process for 25 h. Williamson–Hall method was applied to determine the crystallite size after milling process. To investigate the role of reinforcement particles in consolidation of composite powders, monolithic aluminum powder was examined. Samples were made at different pressures and relationships were established between the compaction pressure and the density of the compacts. The modified Heckel equation was used to assume the pressure effect on yield strength and then was compared with other common equations. The best correlation was obtained when the effect of compaction pressure was considered. Due to lower plastic deformation capacity, the powders with higher content of hard reinforcements exhibited lower compressibility. The results also revealed that the yield strength of compacts, predicted by the mathematical equation, increases with reinforcement addition.

Analysis of the Material and Tablet Formation Properties of four Dioscorea Starches

AbstractThe material and tablet formation properties of starches from four different Dioscorea species, namely White (D. rotundata), Bitter (D. dumetorum), Chinese (D. oppositifolia) and Water yam (D. alata), was characterized to determine their applicability as direct compression excipient. The physicochemical, thermal, morphological and material properties of the starches were investigated. The tablet formation properties were assessed using the 3‐D modeling parameters, the Heckel equation and the force‐displacement profiles. The tablet properties were evaluated using the elastic recovery and compactibility plots. The results indicate that the chemical composition, thermal and material properties of the starches varied considerably among the four species. The sorption isotherms show that the relative humidity (RH) during tablet production and storage should be carefully controlled. The tableting results show that all four starches exhibit similar time dependent deformation (d). The ranking for pressure plasticity (e) was Water &gt; Chinese &gt; White &gt; Bitter, which indicates that Water deforms more easily and Bitter less easily. The ranking for fast elastic decompression was White &gt; Water ≥ Chinese &gt; Bitter. The amylose content, size and shape of the starch granules and specific surface area appears to play a significant role in the compressibility. Thus, White and Water with larger granules and high amylose content exhibited poor compressibility and did not form compacts except at high ρrel,max, while Bitter and Chinese with polygonal shape, small particle size and high specific surface area were more compressible and formed tablets of acceptable crushing force. Thus, Chinese and Bitter could be useful as excipient in direct compression.

Compression, Mechanical and Release Properties of Chloroquine Phosphate Tablets containing corn and Trifoliate Yam Starches as Binders

Purpose: A study was made of the binding properties of trifoliate yam starch, obtained from Dioscorea dumetorum (Pax), in chloroquine phosphate tablet formulations in comparison with official corn starch. Method: Compressional properties were analyzed using density measurements and compression equations of Heckel and Kawakita. The mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets, while drug release properties of the tablets were assessed using disintegration and dissolution times. Results: Tablet formulations containing trifoliate yam starch exhibited faster onset and higher amount of plastic deformation during compression than those containing corn starch. The crushing strength, disintegration and dissolution times of the tablets increased with binder concentration while friability values decreased. Trifoliate yam starch produced tablets with stronger mechanical properties and longer disintegration and dissolution times than those containing corn starch. Conclusion: Trifoliate yam starch would be a better alternative to corn starch in producing uncoated tablets for which high bond strength is essential . Keywords: Trifoliate yam starch, corn starch, binding agent, compression, Heckel equation, Kawakita equation, mechanical properties, drug release> Tropical Journal of Pharmaceutical Research Vol. 5 (2) 2006: pp. 589-596

Evolutions during synthesis of Al–AlN-nanostructured composite powder by mechanical alloying

Abstract High-energy milling technique was used to synthesize Al–10 wt.%AlN-nanostructured composite powder in a planetary ball-mill under argon atmosphere up to 25 h. To show the role of AlN particles, process was conducted for monolithic aluminum. The changes in powder characteristics were investigated by time. Microstructure of powders was studied after different milling times by scanning electron microscope (SEM). The morphological evolutions showed that relative equiaxed powder could be synthesized after 25 h milling. Structural analysis was performed by X-ray diffraction method (XRD) to determine the grain sizes and lattice strain. Furthermore, particle size analysis (PSA) revealed the distribution curvatures. The compressibility behavior of milled powders was studied at different compaction pressures which involve the rearrangement and plastic deformation stages. The modified Heckel equation was used to consider the pressure effect on yield strength as well as reinforcing role of hard AlN particles.

Compaction behavior of uniaxially cold-pressed Bi–Ta composites

Compaction of Bi and Ta powders was performed by uniaxial pressing at room temperature. Post-pressing density was evaluated as a function of the compaction pressure, and indicated that as the Ta content increases there is a reduction in density for comparable pressing conditions. A modified Heckel equation is used to evaluate the compaction behavior. The analysis indicates that the yield pressure increases with increasing Ta content while the Poisson’s ratio is not significantly affected. The yield pressure derived from the analysis compares favorably with published compression testing data for polycrystalline Bi.

Compaction characteristics of ethylcellulose in the presence of some channeling agents: Technical note

This study investigated the effect of some commonly used release enhancers on the compaction characteristics of EC. The wet granulation method of massing and screening was used, and compacts were produced by compressing granules for 60 seconds at various compression pressures. The Heckel equation, used for the analysis of results, showed that EC alone showed better compressibility than formulations with additives. The hygroscopic additives, sorbitol and PEG 4000, produced unusual Heckel plots, while the nonhygroscopic additives, PEG 10 000 and mannitol, produced biphasic Heckel plots. The results also indicate that EC alone exhibited the highest degree of packing in the die, with the addition of mannitol reducing the extent of packing the most. The presence of additives in EC for-mulations increased the pressures at which plastic deformation of EC granules occurred. The extent of this depended on the type of additive, with mannitol imparting the highest resistance to deformation of EC granules and sorbitol the lowest. It can be concluded that additives such as PEG 4000, PEG 10 000, sorbitol, and mannitol, which are often used as channeling agents in sustained-release formulations containing hydrophobic matrix formers, affect the deformation characteristics of EC, with the extent and nature of the effect dependent on the nature of the additive.

Experimental approach of UO2 compaction and analytical modelling of pellet diametric deformations

UO2 powder uniaxial compaction into cylindrical die was studied with a mechanical stress tester Instron, which is able to measure continuously the increase in density, the applied stress and the transmitted stress into both axial and radial direction. For this study, the authors used a spray dried UO2 powder obtained by a wet process, and pressing was performed by single acting compaction until 600 MPa. The relationship between compact density and applied pressure was analysed successively using Niesz's equation between 10 and 100 MPa and Heckel's equation between 100 and 600 MPa. Observations and porosity measurements on green compacts at various degrees of densification permitted to identify which powder particles act on the successive densification stages, previously identified as regimes of Niesz and Heckel for densification. Then, using Thompson's and Heckel's equations, the authors calculated the density distribution into the compact under pressure. Adding analytical equations to calculate springback and shrinkage in function of density, simulated the compact ejection and sintering stages were simulated. This succession of four analytical equations gives the authors a good model of UO2 pellets deformations obtained after a uniaxial powder compaction and sintering. Validation of calculated pellets deformation was performed, measuring diameters at different heights on pellets after sintering for 4 h at 1600°C under flowing Ar/H2 humidified.

The Gurnham equation in characterizing the compressibility of pharmaceutical materials

Limitations of the Heckel equation in characterizing material compression behavior have been well reported. In this work, the Gurnham equation, which was first introduced in chemical engineering, is proposed as an alternate method of evaluating the compressibility of pharmaceutical powders. The Gurnham equation was adapted for tablet compression and the estimated slope parameter c was proposed to represent material compressibility. Data from the compression of four commonly used excipients (microcrystalline cellulose, corn starch, lactose monohydrate, and dibasic calcium phosphate dihydrate) and one drug (acetaminophen) were evaluated using the Gurnham equation. Using compression data at different peak pressures, linear relationships between porosity and ln Pressure of the five materials were obtained. The determined parameter c expresses the compressibility of materials. The analysis of previous experimental data, including granulations, mixtures and co-processed materials also indicates that c might be a representative parameter for material compressibility.

Effects of Pigeon Pea and Plantain Starches on the Compressional, Mechanical, and Disintegration Properties of Paracetamol Tablets

ABSTRACTA study has been made of the effects of pigeon pea starch obtained from the plant Cajanus cajan (L) Millisp. (family Fabaceae) and plantain starch obtained from the unripe fruit of Musa paradisiaca L. (family Musaceae) on the compressional, mechanical, and disintegration properties of paracetamol tablets in comparison with official corn starch BP. Analysis of compressional properties was done by using density measurements, and the Heckel and Kawakita equations, whereas the mechanical properties of the tablets were evaluated by using tensile strength (T-a measure of bond strength) and brittle fracture index (BFI-a measure of lamination tendency). The ranking for the mean yield pressure, Py, for the formulations containing the different starches was generally corn < pigeon pea < plantain starch while the ranking for Pk, an inverse measure of the amount of plasticity, was pigeon pea < plantain < corn starch, which indicated that formulations containing corn starch generally exhibited the fastest onset of plastic deformation, whereas those formulations containing pigeon pea starch exhibited the highest amount of plastic deformation during tableting. The tensile strength of the tablets increased with increase in concentration of the starches while the Brittle Fracture Index decreased. The ranking for T was pigeon pea > plantain > corn starch while the ranking for BFI was corn > plantain > pigeon pea starch. The bonding capacity of the formulations was in general agreement with the tensile strength results. The disintegration time (DT) of the formulation increased with concentration of plantain and corn starches but decreased with concentration of pigeon pea starch. The general ranking of DT values was plantain < pigeon pea < corn starch. Notably, formulations containing pigeon pea starch exhibited the highest bond strength and lowest brittleness, suggesting the usefulness of pigeon pea starch in producing strong tablets with minimal lamination tendency. Plantain starch, on the other hand, would be more useful where faster disintegration of tablet is desired. The results show that the starches could be useful in various formulations depending on the intended use of the tablets with the implication that the experimental starches can be developed for commercial purposes.