Heckel Analysis Research Articles

Revolutionizing fast disintegrating tablets: Harnessing a dual approach with porous starch and sublimation technique

This study investigates the transformation of neat starch (NS) from mung beans into porous starch (PS) for the formulation of fast-disintegrating tablets (FDTs) using the sublimation technique, contrasting their performance with superdisintegrants such as sodium starch glycolate (SSG) and croscarmellose sodium (CS). Camphor was used as a sublimating agent. The interaction between drug and excipients was analyzed using Fourier-transform infrared spectroscopy (FTIR), while preformulation assessments were conducted on powder blends. Model drug Diclofenac sodium (DL)-loaded FDTs were prepared via direct compression technique. Thermal behavior and crystalline properties were evaluated using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), respectively. Compressibility of tablets was assessed through Heckel and Kawakita analyses. Post-compression evaluations encompassed hardness, thickness, in vitro disintegration, and dissolution studies. FTIR analysis indicated the absence of chemical interactions among constituents, while precompression analyses confirmed favorable flow properties of the blends. Heckel analysis supported the material's notable compressibility. Microscopic examination revealed the formation of pores on the tablet surface due to the sublimation process. Integration of PS significantly accelerated the disintegration time of FDTs, with durations ranging from 50 to 82 s, compared to 76–104 s for NS-FDTs. While PS-FDTs exhibited a longer disintegration time compared to SSG, they demonstrated faster disintegration compared to croscarmellose sodium. A significant disparity (p<0.01) in drug release at 60 min was observed between SSG and PS-FDTs, with DP3 achieving 97.65 % drug release. Most batches followed the Korsmeyer-Peppas model, except for DN2 and DN3, which adhered to Higuchi-matrix drug release kinetics. Stability assessments after 90 days revealed no significant differences (p>0.05). Conclusively, this study highlights the effectiveness of PS and the sublimation method in creating FDTs with enhanced drug release properties.

Optimizing release properties of tablets from Spondias mombin spray-dried leaves extract using dry and melt granulation

This study aimed to investigate the efficacy of conventional dry granulation (slugging) and twin-screw melt granulation (TSMG) as downstream processing methods to enhance the technological properties, such as flowability and tabletability, of spray-dried plant extracts (SDE). A hydrophilic (Polyethylene glycol 6000-PEG) and a lipophilic binder (glyceryl dibehenate-GBE) were explored for the melt granulation process. Compression behavior and powder rheological properties of SDE and its granules were investigated. Compression analysis by in-die Heckel analysis explained the SDE's poor mechanical properties resulting in poor compact integrity in addition to the poor flow properties of the SDE. Despite the success of granulation strategies to improve the material's flowability and tabletability, the TSMG granules exhibited better performance than slugged granules. Regarding formulation, the lipophilic binder facilitated greater plastic deformation than the hydrophilic binder, enhancing the release of formulations across different profiles from controlled release, adjusting the granules quantity, to immediate-release tablets containing either brittle or plastic fillers. In conclusion, TSMG combined with a lipophilic melt binder emerged as a promising technology for overcoming the challenges of poor tabletability and modifying the release profile of ellagitannin from SDE.

The Increase in the Plasticity of Microcrystalline Cellulose Spheres' When Loaded with a Plasticizer.

Compaction pressure can induce an undesirable solid-state polymorphic transition in drugs, fragmentation, loss of coated pellet integrity, and the decreased viability and vitality of microorganisms. Thus, the excipients with increased plasticity can be considered as an option to decrease the undesirable effects of compaction pressure. This study aims to increase the plasticity (to reduce the mean yield pressure; Py) of dried microcrystalline cellulose (MCC) by loading it with a specially selected plasticizer. Diethyl citrate (DEC), water, and glycerol were the considered plasticizers. Computation of solubility parameters was used to predict the miscibility of MCC with plasticizers (possible plasticization effect). Plasticizer-loaded MCC spheres with 5.0 wt.% of water, 5.2 wt.% of DEC, and 4.2 wt.% glycerol were obtained via the solvent method, followed by solvent evaporation. Plasticizer-loaded formulations were characterised by TGA, DSC, pXRD, FTIR, pressure-displacement profiles, and in-die Heckel plots. Py was derived from the in-die Heckel analysis and was used as a plasticity parameter. In comparison with non-plasticized MCC (Py = 136.5 MPa), the plasticity of plasticizer-loaded formulations increased (and Py decreased) from DEC (124.7 MPa) to water (106.6 MPa) and glycerol (99.9 MPa), and that was in full accordance with the predicted miscibility likeliness order based on solubility parameters. Therefore, water and glycerol were able to decrease the Py of non-plasticized MCC spheres by 16.3 and 30.0%, respectively. This feasibility study showed the possibility of modifying the plasticity of MCC by loading it with a specially selected plasticizer.

Enhancement of material attributes of poorly compressible metformin hydrochloride through coprocessing with hydroxypropyl cellulose (HPC-L) using coprecipitation (CPT)

Coprocessing involves integration of multiple substances to improve the physical, chemical, mechanical, and biopharmaceutical properties of a material. Coprocessing is a promising technique in the pharmaceutical industry which support both drug substance and drug product processes. When active pharmaceutical ingredients (APIs) are coprocessed with excipients, it can enable direct compression and continuous manufacturing. Hydroxypropyl cellulose (HPC-L), a commonly used excipient in pharmaceutical formulations, can enhance drug stability, solubility, and bioavailability. In this study, we have employed coprecipitation (CPT) to coprocess metformin hydrochloride (MET) with HPC-L, resulting in the formation of agglomerates with improved physical attributes without any risk of polymorphic changes. Acetone/acetonitrile and heptane were used as solvent and antisolvent, respectively. Screening study revealed that the use of a rotor stator helps to control the size of metformin hydrochloride and HPC-L agglomerates (M-CPT) without negatively impacting bulk density and powder flow properties. The CPT agglomerates showed residual solvent levels within the specified ICH limits. Powder rheology results demonstrated a sixfold increase in FFC of M-CPT compared to neat MET. The compressibility, tabletability, compactability, and “In-Die” Heckel analysis data further suggested that the M-CPT agglomerates are directly compressible with no observable changes in the dissolution profile of MET. Overall, this study demonstrates application of CPT approach to tune the physical and mechanical properties, and HPC-L can be used as an excipient of choice for CPT technique to improve the compressibility and flowability of APIs.Graphical

Evaluation of In-Die Compression Data for a Deeper Understanding of Altered Excipient Properties upon Temperature Rise

The thermodynamic analysis of tablet formation includes the thermal and mechanical analysis during compression. The aim of this study was to evaluate alterations of force–displacement data upon temperature rise as an indicator for changed excipient properties. The tablet press was equipped with a thermally controlled die to imitate the heat evolution from tableting on an industrial scale. Six predominantly ductile polymers with a comparably low glass transition temperature were tableted at temperatures ranging from 22-70°C. Lactose served as a brittle reference with a high melting point. The energy analysis included the net and recovery work during compression, from which the plasticity factor was calculated. The respective results were compared to the changes in compressibility obtained via Heckel analysis. Elevated temperatures reduced the necessary work for plastic deformation for the ductile polymers, which was reflected in decreasing values for the net work of compaction and the plasticity factor. The recovery work slightly increased for the maximum tableting temperature. Lactose showed no response to temperature variations. Changes in the net work of compaction showed a linear correlation to the changes in yield pressure, which could be correlated to the glass transition temperature of a material. It is therefore possible to detect material alterations directly from the compression data, if the glass transition temperature of a material is sufficiently low.Graphical

An approach for predicting the true density of powders based on in-die compression data

Helium pycnometry, a commonly used technique for measuring the true density of powders, is sensitive to the release of volatiles during measurement. This can lead to over-estimated true density, and as such, an accurate method for determining the true density of powders containing volatile components is needed. Here, a method based on in-die compression data obtained with a compaction simulator was assessed. Specifically, the stress transmission coefficient (STC), measured using an instrumented die, was used to predict the in-die Heckel mean yield pressure (Py). A true density was derived by repeatedly performing a Heckel analysis using iteratively estimated true density values until the predicted Py value from the measured STC value is obtained from in-die density - pressure data. This novel method was validated using a set of water-free powders. Using crystalline hydrates, we further showed that the calculated true densities were closer to values calculated from crystal structure than those from helium pycnometry. Hence, this method may be used for determining the true density of powders from their STC values.

Effect of Particle Size and Pressure on the Transport Properties of the Fast Ion Conductor t‐Li7SiPS8

AbstractAll‐solid‐state batteries promise higher energy and power densities as well as increased safety compared to lithium‐ion batteries by using non‐flammable solid electrolytes and metallic lithium as the anode. Ensuring permanent and close contact between the components and individual particles is crucial for long‐term operation of a solid‐state cell. This study investigates the particle size dependent compression mechanics and ionic conductivity of the mechanically soft thiophosphate solid electrolyte tetragonal Li7SiPS8 (t‐LiSiPS) under pressure. The effect of stack and pelletizing pressure is demonstrated as a powerful tool to influence the microstructure and, hence, ionic conductivity of t‐LiSiPS. Heckel analysis for granular powder compression reveals distinct pressure regimes, which differently impact the Li ion conductivity. The pelletizing process is simulated using the discrete element method followed by finite volume analysis to disentangle the effects of pressure‐dependent microstructure evolution from atomistic activation volume effects. Furthermore, it is found that the relative density of a tablet is a weaker descriptor for the sample's impedance compared to the particle size distribution. The multiscale experimental and theoretical study thus captures both atomistic and microstructural effects of pressure on the ionic conductivity, thus emphasizing the importance of microstructure, particle size distribution and pressure control in solid electrolytes.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling.

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.

Effect of starch, cellulose and povidone based superdisintegrants in a QbD-based approach for the development and optimization of Nitazoxanide orodispersible tablets: Physicochemical characterization, compaction behavior and in-silico PBPK modeling of its active metabolite Tizoxanide

The objective of the study was to develop a QbD based orodispersible Nitazoxanide 200 mg tablets its in-silico PBPK modeling. The central composite design was applied to study the effect of four different superdisintegrant i.e., starch and cellulose based (sodium starch glycolate, pre-gelatinized starch, croscarmellose sodium), and crospovidone with microcrystalline cellulose as independent variables on disintegration time and % drug release. The Heckel analysis was applied to determine the compression behavior of the formulations which revealed a yield pressure in the range of ∼119 MPa–∼138 MPa. Moreover, the hardness of the tablets increased with the compression force and was largely independent of the disintegration time (<3 min for a maximum pressure of ∼138 MPa) owing to the role of superdisintrgrants in the formulations. The quality attributes suggest that the formulations containing microcrystalline cellulose (11–15%) with sodium starch glycolate (8%), pregelatinized starch (7.185%), croscarmellose sodium (2.755%), and crospovidone (5%) at the maximum desirability (0.799–0.902) exhibited minimum disintegration time and maximum % drug release. Their dissolution data (pH 1.2) were applied to predict the pediatric plasma profile of the active metabolite Tizoxanide by PBPK modeling. The QbD-based approach was successfully applied in designing Nitazoxanide 200 mg orodispersible tablets.

Influence of temperature on the compression behavior of pharmaceutical excipients

Tableting on an industrial scale is characterized by an increase in temperature, which is dependent on numerous factors. The aim of this study was to examine the glass transition temperature of frequently used polymers as a critical parameter on tablet properties. Tablets were produced in a tablet press equipped with a temperature-controlled die at four different temperatures ranging from 22 to 70 °C. While pure polymers were characterized for their temperature-dependent compressibility behavior using Heckel analysis, tableting was performed from binary blends containing lactose as a filler and the polymer to be examined (ratio 9:1). Tablets were characterized in terms of tabletability, compactibility and their correlation with the glass transition temperature. The decrease in mean yield pressure upon temperature rise could clearly be correlated to the glass transition temperature of a given polymer, whereby polymers with low glass transition temperatures proved to be more responsive to temperature changes. Tablet properties were equally affected by the applied temperature despite the low polymer content. Thus, polymers with higher glass transition temperatures should be preferred in a full-production scale to avoid an alteration of tablet characteristics, whereas polymers with lower glass transition temperatures could be advantageous if a change of material properties is desired.

Negative porosity issue in the Heckel analysis: A possible solution

A parameterization of compaction simulator generated dynamic compression profile with a few grams of powder provides important information about the material deformation and compact elasticity. The Heckel equation is by far the most popular choice among pharmaceutical scientists for such parametrization. A general approach of Heckel analysis uses pycnometric powder density (ρP0) for relative density calculation. However, as ‘in-die’ tablet bulk density at applied compression pressure (ρBP) becomes greater than or equal to the measured ρP0, the general approach typically poses a negative porosity challenge at high compression pressure regions. It is only theoretically possible to have a tablet with zero or negative porosity. Negative porosity may be detected during ‘in-die’ compression analysis, but it will not exist after ejection of the tablet in practical aspect. Thus, the present work proposes a new approach to using pycnometric tablet density (ρPP) in the relative density calculations of Heckel analysis. This ρPP may be a better representation of actual tablet particle volume, as it is composed of non-accessible intra-particulate pores, which are broken under applied compression pressure. A new approach showed its immunity for Heckel high-pressure negative porosity. It enables the utilization of the compression and decompression phases of dynamic compression profiles to evaluate macroscopic compaction performance. The proposed approach was validated with a reported modified Heckel approach. The Heckel parameters computed with both methodologies for microcrystalline cellulose and lactose were not statistically different. However, a modified Heckel approach was unable to compute Heckel parameters of poorly compacting starch unlike the new approach. A modified Heckel approach became invalid during starch compaction at low compression pressures (below 400 MPa), where starch was forming weaker but still intact tablets. Certainly, a complete Heckel profiling with a new approach could save time and costs in an early development stage for designing and screening scientifically based lead prototype formulations.

Compressibility analysis as robust in-die compression analysis for describing tableting behaviour

Abstract Objectives Compressibility of materials is determining the tableting behaviour and tablet properties during and after manufacturing. The compressibility constant has not been investigated as an in-die method yet and was therefore compared with the Heckel analysis for describing the compressibility of materials during tableting in the present study. Methods Various parameters influencing tableting, such as compression pressure, compression speed and punch diameter, were used to analyse the robustness of both methods and to evaluate the informative value of the compression parameters. Twelve common pharmaceutical excipients were used to cover a wide range of material properties. Key findings The compressibility constant was successfully applied as an in-die method and proved to be more robust against the influencing parameters during tableting than the Heckel analysis. A good correlation between the out-of-die and in-die method was found for both methods but could not be observed between the compressibility constant and the yield pressure from Heckel analysis. The methods are both describing the volume reduction of materials under pressure but focus on different material properties. Conclusions For material characterisation in the field of tableting, the compressibility constant can be additionally applied in the future to be able to determine another compressibility parameter in combination with the yield pressure.

Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression.

Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab®14SD, 19.53–26.91%), microcrystalline cellulose (MCC PH102, 32.86–43.31%), pre-gelatinized starch (Starch-1500, 10.96–15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150–300 MPa) and tableting speed (1200–2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar® tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar® tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F0.05). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression.

Modified crystal habits of glimepiride to improve manufacturing processability

Form I of glimepiride (GMP) with irregular crystal habit was chosen to develop an appropriate crystal habit to improve its dissolution and other material attributes such as cohesiveness, flow behavior, plastic deformation, yield pressure, compressibility, compactibility, and tensile strength. Modified habits generated were hexagonal (GMP-A), rhombohedral (GMP-B), and tabular (GMP-C). Scanning electron microscopy (SEM) and generated morphology confirmed the shape of the habits. Solid-state properties were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA), which confirmed that no polymorphic transition occurred. Flow characterization, Kawakita, and Heckel analysis, studies on tensile strength, compressibility, compactibility, and dissolution proved that modified habits have better flow, less cohesive nature, linear plastic deformation, low yield pressure, better compressibility, compactibility, tensile strength, and dissolution profile over irregular crystal habit (p < 0.05). Amongst the obtained habits, GMP-C performs better in all aspects over the rest of the habits and hence will be a good choice for further formulation development.

Compression Modulus and Apparent Density of Polymeric Excipients during Compression-Impact on Tabletability.

The present study focuses on the compaction behavior of polymeric excipients during compression in comparison to nonpolymeric excipients and its consequences on commonly used Heckel analysis. Compression analysis at compaction pressures (CPs) from 50 to 500 MPa was performed using a compaction simulator. This study demonstrates that the particle density, measured via helium pycnometer (ρpar), of polymeric excipients (Kollidon®VA64, Soluplus®, AQOAT®AS-MMP, Starch1500®, Avicel®PH101) was already exceeded at low CPs (<200 MPa), whereas the ρpar was either never reached for brittle fillers such as DI-CAFOS®A60 and tricalcium citrate or exceeded at CPs above 350 MPa (FlowLac®100, Pearlitol®100SD). We hypothesized that the threshold for exceeding ρpar is linked with predominantly elastic deformation. This was confirmed by the start of linear increase in elastic recovery in-die (ERin-die) with exceeding particle density, and in addition, by the applicability in calculating the elastic modulus via the equation of the linear increase in ERin-die. Last, the evaluation of “density under pressure” as an alternative to the ρpar for Heckel analysis showed comparable conclusions for compression behavior based on the calculated yield pressures. However, the applicability of Heckel analysis for polymeric excipients was questioned in principle. In conclusion, the knowledge of the threshold provides guidance for the selection of suitable excipients in the formulation development to mitigate the risk of tablet defects related to stored elastic energy, such as capping and lamination.

Air entrapment during tablet compression – Diagnosis, impact on tableting performance, and mitigation strategies

Air entrapment during powder compression, a phenomenon that can cause tablet defects upon decompression and ejection, was diagnosed for celecoxib powder by comparing its in-die elastic recovery profiles with and without precompression prior to the main compression. Without precompression, the elastic recovery of celecoxib compacts significantly increased from ∼4% at a main compaction pressure of 150 MPa to ∼14% at and above 200 MPa. The large increase in elastic recovery is eliminated when a precompression step is employed. The deaeration of powder by precompression resulted in higher tablet strength, accompanied by lower tablet porosity. Thus, precompression is an effective strategy to mitigate the deleterious effects of air entrapment in tablet manufacturing. We also found that, although entrapped air caused significantly higher elastic recovery, it does not affect the plasticity parameter derived from an in-die Heckel analysis.

Beyond Brittle/Ductile Classification: Applying Proper Constitutive Mechanical Metrics to Understand the Compression Characteristics of Pharmaceutical Materials

Active pharmaceutical ingredients (API) and excipients are often classified as ‘brittle’ or ‘ductile’ based on their yield pressure determined through the Heckel analysis. Such a brittle/ductile classification is often correlated to some measure of elasticity, die-wall stresses, and brittle fracture propensities from studies performed with a handful of model excipients. This subsequently gives rise to the presumption that all ductile materials behave similarly to microcrystalline cellulose (MCC) and that all brittle materials to lactose, mannitol, or dicalcium phosphate. Such a ‘one-size-fits-all’ approach can subsequently lead to inaccurate classification of APIs, which often behave very differently than these model excipients. This study compares the commonly reported mechanical metrics of two proprietary APIs and two classical model excipients. We demonstrate that materials classified as ‘ductile’ by Heckel's ‘standards’ may behave very differently than MCC and in some cases may even have a propensity for brittle failure. Our data highlight the complexity of APIs and the need to evaluate a set of mechanical metrics, instead of binary assignments of ductility or brittleness based on quantities that do not fully capture the tableting process, to truly optimize a tablet formulation as part of the overall target product profile.

Mean yield pressure from the in-die Heckel analysis is a reliable plasticity parameter

Despite the ability to characterize the plasticity of powders in a material-sparing and expedited manner, the in-die Heckel analysis has been widely criticized for its sensitivity to several factors, such as particle elastic deformation, tooling size, lubrication, and speed. Using materials exhibiting a wide range of mechanical properties, we show that the in-die Py correlates strongly with three established plasticity parameters obtained from the out-of-die Heckel analysis, Kuentz-Leuenberger analysis, and macroindentation. Thus, the in-die Py is a reliable parameter for quantifying powder plasticity in a material-sparing and expedited manner.

Modulation of the powder properties of lamotrigine by crystal forms

The mechanical properties of powders determine the ease of manufacture and ultimately the quality of the oral solid dosage forms. Although poor mechanical properties of an active pharmaceutical ingredient (API) can be mitigated by using suitable excipients in a formulation, the effectiveness of that approach is limited for high dose drugs or multidrug tablets. In this context, improving the mechanical properties of the APIs through solid form optimisation is a good strategy to address such a challenge. This work explores the powder and tableting properties of various lamotrigine (LAM) solid forms with the aim to facilitate direct compression by overcoming the poor tabletability of LAM. The two drug-drug crystals of LAM with nicotinamide and valproic acid demonstrate superior flowability and tabletability over LAM. The improved powder properties are rationalised by structure analysis using energy framework, scanning electron microscopy, and Heckel analysis.

Understanding Deformation Behavior and Compression Speed Effect in Gabapentin Compacts.

Deformation mechanism and strain rate sensitivity of gabapentin powder was investigated in this work. Heckel analysis, specific surface area and indentation hardness measurements revealed an intermediate yield pressure and brittle fracture as the dominant type of deformation mechanism during consolidation. Strain rate sensitivity of gabapentin was studied by compressing it at 1mm/min and 500mm/min compression speeds. Gabapentin demonstrated an atypical strain rate sensitivity in compactibility profile (tensile strength vs. solid fraction). Compacts of gabapentin compressed at fast speed showed an increase in tensile strength when compared with those compressed at slow speed. To understand the effect of compression speed on gabapentin's compactibility, PXRD analysis, surface area analysis, indentation hardness measurements, and consolidation modeling were performed. PXRD analysis carried out on compacts revealed no effect of speed on the physical solid-state stability of gabapentin. Specific surface area of compacts made at fast speed was higher than that of compacts made at slow speed. Indentation measurements performed on gabapentin compacts showed higher values of hardness in the case compacts made at fast speed. It was identified that at the fast compression speed, gabapentin shows greater particle fragmentation and form compacts with smaller pores.