Mean Yield Pressure Research Articles

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.

CELLULOSE NANOCRYSTAL-INCORPORATED CO-PROCESSED EXCIPIENT IN TABLET FORMULATION

The objective of the current work is to develop a new co-processed excipient based on cellulose nanocrystals and investigate its pharmaceutical excipient properties. Cellulose nanocrystals were isolated from the pseudostem of Musa balbisiana, following TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-mediated oxidation, and then co-processed with potato starch by the wet granulation method. Physicochemical properties, including the flow property, consolidation characteristics and rate of consolidation, were investigated, and a Kawakita plot was also generated. The compressibility, compactibility and tabletability of the novel excipient were determined. The equivalent circle diameter of the excipient particle was calculated as 4.09±0.90 μm, exhibiting a fair to passable flow property. The mean yield pressure from the Heckel plot was found to be 82.64 MPa, indicating its ability to undergo plastic deformation at relatively lower compression pressures. When compared to sodium starch glycolate, a standard tablet disintegrant, the cellulose nanocrystal-based co-processed excipient produced better dissolution of the model drug paracetamol.

Nicotinamide-based agglomerates of ibuprofen: formulation, solid state characterization and evaluation of tableting performance with in-silico investigation

BackgroundThe objective of the present investigation was to obtain directly compressible agglomerates of ibuprofen with nicotinamide by a quasi-emulsification solvent diffusion technique. Ibuprofen-nicotinamide agglomerates were prepared by quasi-emulsification solvent diffusion technique using ethanol (good solvent), water (poor solvent), and chloroform (bridging liquid). The prepared agglomerates were characterized by ATR-FTIR, powder X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy and were evaluated for tableting performance and in vitro drug release. To appropriately identify the hydrogen bonding sites, a thorough understanding of the structures of API and coformer is necessary, hence molecular docking approach was implemented to depict the interaction between the proposed coformer and COX-2 protein (PDB Id:4PH9).ResultsThe percent yield of agglomerates was in the range of 85–98 w/w%, and drug content for all batches was in the range of 96–99%. The microphotographs showed irregular circularly shaped agglomerates. ATR-FTIR study showed a strong possibility of hydrogen bonding between ibuprofen and nicotinamide. The crystallinity of ibuprofen was slightly reduced and confirmed by P-XRD and DSC. Crushing strength and friability studies showed good handling qualities of ibuprofen agglomerates. Heckel plot studies showed low mean yield pressure and high tensile strength, indicating excellent compressibility and compactibility of ibuprofen agglomerates. More than 90% drug release was obtained within 60 min in PBS (pH 7.4). The docking studies revealed that nicotinamide individually has –CDOCKER energy 16.8109 where coformer showed 29.0584, which indicates coformer has a better binding affinity to target as compared to nicotinamide individual.ConclusionsIt can be concluded that the agglomerates improved the dissolution, tableting performance, and solid-state properties of ibuprofen and hence can be useful to improve the therapeutic performance of ibuprofen.Graphic

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.

Processability and Oral Bioavailability Improvement of Itraconazole by Particle Engineering Technique.

The current study aimed to improve the processability and oral bioavailability of itraconazole (ITZ) via spherical agglomeration. ITZ-spherical agglomerates (ITZ-SA) and ITZ-poloxamer 407-spherical agglomerates (ITZ-PLX-SA) were optimized using Box-Behnken design. Here, the drug release was affected by polymer concentration and stirring speed, whereas particle size was altered by stirring speed, polymer concentration, and amount of bridging liquid. Heckel and Kawakita studies showed a reduction in mean yield pressure and remarkably lowered 1/b value than ITZ, indicating better compactibility and flowability of ITZ-PLX-SA. Physicochemical interactions were not observed during the process, as indicated by ATR-FTIR, DSC, and XRPD. The significant improvement in % drug release of ITZ-PLX-SA was attributed to better wettability and the presence of polymer than ITZ-SA and ITZ. The pharmacokinetic study in rats indicated fivefold enhanced Cmax and twofold improved AUC for ITZ-PLX-SA than plain drug. Thus, spherical agglomeration could improve overall processability and pharmacokinetic profile of ITZ.

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.

Effects of carboxymethylated gum obtained from Entandophragma angolense tree on the compressional and release properties of ibuprofen tablets

The incorporation of modified polymers in drug formulations is primarily due to their low toxicity, affordability, availability, compatibility with biological membranes, economic feasibility and bio-degradability.This study investigated the compressional and release characteristics of ibuprofen tablet formulations containing natural and modified Entandophragma angolense gum. Entandophragma angolense gum (ENTA) was extracted and modified by carboxymethylation to yield CENTA. Ibuprofen tablets containing varying binder concentrations (2.5-10% w/w) of ENTA and CENTA (compared with gelatin BP) were formulated by wet granulation. Crushing strength (CS) and friability (FR) were used in assessing the mechanical properties of the tablets, while disintegration and dissolution times accounted for drug release parameters. Density measurements, Kawakita equations and Heckel plots were used to assess the compressional properties of the formulations. The results were analysed using ANOVA at ɑ0.05. Generally, there was a direct relationship between the concentration of the polymers and the CS of the tablets, while an inverse relationship was observed for FR. The CS ranked ENTA > CENTA > gelatin BP. Carboxymethylation of ENTA enhanced drug release (t30% and t80%). Formulations containing CENTA had a slower and faster onset of plastic deformation; mean yield pressure (Py), ranked ENTA > CENTA > gelatin BP. A measure of the rearrangement phase at the early stages of compression (DB) was highest for CENTA at all concentrations. CENTA compared favourably with gelatin BP and showed better mechanical and release characteristics than ENTA. Also, CENTA shows good potential as a binder in fast disintegrating ibuprofen tablets, especially when incorporated at low concentrations.

Comparative Evaluation of the Disintegrant Properties of Starches from Three Cultivars of Dioscorea rotundata (Poir)

Poir starches from three cultivars (Lagos, Giwa, and Sule) were evaluated asexo-disintegrants (5 and 10%w/w) in paracetamol tablet formulations to determine whether the similarity in their physicochemical and material properties translates to performance in tablet formulation. The tablets were prepared by wet granulation and were evaluated for compressional properties (Heckel equation), mechanical strength (crushing strength and friability), and drug release (disintegration and dissolution times). Plastic deformation occurred in all tablets with rank order for the onset of plastic deformation Lagos>Giwa>Sule. An increase in the concentration of disintegrants in the tablets led to a decrease in mean yield pressure, total relative precompression density, and relative density at low pressure, but an increase in relative density at zero pressure. The crushing strength and disintegration times of the tablets were dependent on the disintegrants' concentration. All tablets passed the disintegration test (≤15min) with tablets containing the Sule cultivar producing the fastest disintegration (p<0.05). Tablets containing 10% of the Sule cultivar had the fastest release of paracetamol (t80=32.1min), though it failed the compendial standard for immediate release tablets (t80≤30min). Starches from the three cultivars despite their similar physicochemical and material properties exhibited different disintegrant properties and could find different applications as excipients in tablet formulations.

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.

Application of modified SeDeM expert diagram system for selection of direct compression excipient for liquisolid formulation of Neusilin® US2

In the present investigations, the SeDeM expert diagram system, modified to include two important compression properties, i.e. mean yield pressure, Py, and compactibility parameter, σtmax, was used to identify a diluent most suitable for the direct compression of a liquisolid formulation of Neusilin® US2 (50NEU). The mean incidence values of 50NEU demonstrated that it had poor flowability and compactibility, and was highly hygroscopic. Three commonly used directly compressible tablet diluents, viz. lactose monohydrate, microcrystalline cellulose, and dibasic calcium phosphate, selected based on their index of good compressibility (IGC) values were evaluated for their usefulness for direct compression of 50NEU. Mathematical equations based on the linear and power mixing rules were used to calculate the percentage of diluent required for direct compression. The powder blends prepared using lactose monohydrate resulted in fragile tablets, dibasic calcium phosphate exhibited poor compactibility, however, powder blends containing microcrystalline cellulose resulted in tablets with acceptable compactibility. This demonstrated the significance of a rational selection of excipients based on their SeDeM parameters rather than the IGC values. Additionally, the study results showed that the modified SeDeM expert system was superior to the conventional SeDeM system for the selection of diluent for direct compression.

Structure-Property Relationship of Amorphous Maltitol as Tableting Excipient.

Maltitol shows interesting properties compared with mannitol or sorbitol, two other polyols, which are widely used as a pharmaceutical excipients for tablet compaction. For this study, the properties of an amorphous polyol, maltitol, were investigated using a tablet press simulator. The aim of this study was to evaluate the behavior of amorphous maltitol compared to SweetPearl® P 200, a pure product, and SweetPearl® P 300DC, a textured crystalline maltitol excipient for direct compression. The physicochemical and pharmacotechnical properties were compared, revealing a major change in properties after amorphization. The study of the tabletability, mean yield pressure, elastic properties, etc. shows that the compression behavior of amorphous powders has been significantly altered. The results showed specific properties of amorphous maltitol with good tabletability at low compaction pressure. The stability of the amorphous and the evolution of its behavior in compression were then studied, showing a direct link between its recrystallization and the change in its properties. The use of a stabilizing agent, maltotriitol, slowed down the recrystallization, maintaining the specific properties of the amorphous material in compression for a longer period of time.

A model to simultaneously evaluate the compressibility and compactibility of a powder based on the compression ratio.

The present study aimed to establish a new model to evaluate the compressibility and compactibility of materials simultaneously. Eighteen types of pharmaceutical excipients were studied via direct compaction. The model was established as CR=y0+Ae-bP, r2≥0.9684 (where CR is the compression ratio and P is the compaction force and y0, A, b is constant). The physical meaning of y0 and b were studied in the model. The results show that y0 has a strong correlation with the mean yield pressure (Py, r=0.609, P<0.01), which is the evaluation parameter of material compressibility. b has a strong correlation with the evaluation parameter of material compactibility, such as the slope of the tensile strength versus compaction force (kA, r=0.780, P<0.01) and the tensile strength versus porosity (Ryshkewitch-Duckworth equation) (kR, r=0.658, P<0.01). The results of model experiments (r=0.767, 0.895, and 0.756), literature, and repeatability verification demonstrated that the main parameters y0 and b in the established model have good applicability and repeatability. Therefore, the newly established model is reliable for evaluating both the compressibility and the compactibility of powders. The model provides support for further research into powder properties and tablet preparation.

Determination of maximum flowable liquid-loading potential of Neusilin® US2 and investigation of compressibility and compactibility of its liquisolid blends with PEG (400)

The objective of the present study was to determine the maximum flowable liquid-loading potential of a solid carrier material (Neusilin® US2) and to investigate the compressibility and compactibility of its liquisolid blends with PEG (400). Liquid-solid blends using an increasing amount of a non-volatile liquid (PEG 400) sorbed onto the solid carrier were prepared to determine its flowable liquid-loading potential. The solid carrier and liquisolid blends were then compressed at various compression pressures. The compression data were fitted into Walker, Kawakita, and Heckel equations to determine the compressibility of Neusilin® US2 and the liquisolid systems, and into Leuenberger and Ryshkewitch-Duckworth equations to determine their compactibility. It was observed that Heckel and Leuenberger equations were the most suitable mathematical models to quantify the compressibility and compactibility of solid carrier and its liquisolid blends, respectively. The values of mean yield pressure, Py, calculated from Heckel plot and compactibility parameter, σtmax, determined using Leuenberger equation were found to decrease with an increase in the liquid-loading. In addition, a good correlation was observed between the mean yield pressure, Py, and compactibility parameter, σtmax, of the liquisolid systems. Thus in the present study, compressibility and compactibility of liquisolid systems were successfully determined for formulation development of liquisolid compacts.

Mechanics of tablet formation: a comparative evaluation of percolation theory with classical concepts

The present study is based on the fundamentals of percolation theory and its application in understanding compression and compaction of powder materials. Four materials, i.e. carbamazepine, microcrystalline cellulose, crospovidone and croscarmellose sodium, with dissimilar deformation and compaction behavior were selected to validate the hypotheses of percolation phenomenon. The values of two percolation thresholds, i.e. bond and site, corresponding to the lower and intermediate compression pressures, were determined using Heckel equation. The compactibility of powder materials was evaluated using classical models as well as the power law equation. The values of percolation thresholds were found to better assess the deformation behavior of powder materials compared to the values of mean yield pressure. The power law equation demonstrated better prediction of compactibility of powder materials compared to the classical models. The value of the critical exponent, q, determined using power law equation by plotting tensile strength vs. normalized relative density of powder compacts was found to be closer to the theoretical value of 2.70. Furthermore, the theoretical knowledge of percolation thresholds of individual powder components in the binary mixture was found to be helpful in improving compaction properties of the poorly compactible material, i.e. carbamazepine. Thus percolation theory can be helpful in predicting compression and compaction behavior of powder materials and serve as a potent tool for the successful design of tablet formulations.

Improved micromeritics, packing properties and compressibility of high dose drug, Cycloserine, by spherical crystallization

Cycloserine, a high dose anti-tuberculosis agent, possesses poor flow properties and compression behaviour. The present study was aimed at improving the flowability, packing properties and compressibility of Cycloserine by spherical crystallization. Cycloserine was dissolved in a water and crystallised by pouring into anti-solvent, 1-Butanol, in presence of ethyl acetate which acts as a bridging liquid for formation of agglomeration. Further, spherical agglomeration process for Cycloserine was statistically optimized using the central composite design, keeping the ‘rate of stirring’ and ‘amount of bridging liquid’ as an independent factors and average particle size as the response. Optimized batch of Cycloserine spherical agglomerates (Cyc-SA) was further evaluated for sieve analysis, solid state characterization studies and compaction behaviour (Kawakita analysis and Heckel study). The uniform spherical agglomerates were revealed in microphotographs of scanning electron microscopy while no chemical alteration in the Cycloserine was indicated by X-Ray powder diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy during the crystallization. The excellent flow properties of Cyc-SA were demonstrated by Carr's index, Hausner ratio and Kawakita parameters as compare to plain drug. The enhanced particle size and uniform distribution of agglomerates have also contributed to improve flow properties of Cycloserine. Similarly, Heckel parameters like mean yield pressure and yield strength displayed superior compressibility of Cyc-SA. Thus, spherical crystallization would be interesting technique for improving processability of high dose drug like Cycloserine.

Deformation behavior of crystallized mannitol during compression using a rotary tablet press simulator

Mannitol is commonly used as a pharmaceutical excipient for tablets; the most widely used oral dosage form for drug delivery. For tableting, mannitol is provided in two different forms: native crystals and textured particles. In order to optimize its formulation, a good understanding of the mechanical behavior mechanism of mannitol is necessary. Thus, the aim of this study is to evaluate the deformation mechanism of native mannitol crystals presenting different particle sizes. Pharmaco-technical and compression studies were performed using mannitol with different mean diameters (160 µm, 50 µm and 25 µm). Lactose (monohydrate) and microcrystalline cellulose were used as brittle and plastic reference materials, respectively. Tableting tests and mathematical models, HECKEL and WALKER, were used to study the deformation mechanism of mannitol (β). Mean Yield Pressure (Py) and WALKER coefficient (W) values showed that the studied crystalline mannitol presents a deformation mechanism close to brittle material. A particle-size analyzer was used at different pulverization pressures to show the high sensibility of the mannitol particles to fragmentation when exposed to high pressures, especially for particles presenting 160 µm size. Scanning Electron Microscopy (SEM) was used to show the fragmentation after high-pressure measurements.

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90–97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and Cmax. A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

Chitin’s Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments

Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure “Py” shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation.

A new approach to optimize compression of paraffin materials: influence of particles size and shape

The work described in this paper investigates the behaviour of paraffin material under pressure. Compressibility has been widely described in the literature but the behaviour of paraffin materials under compression is not well known. This study intends to highlight the influence of particle size and shape of paraffin material on their compressibility. This is of major interest for the candle industry. Indeed, one of the main forming processes is pressing of paraffin powder. For this purpose, particle size and shape were characterized according to a digital image analysis approach and compressibility was measured by compressing the paraffin into a mould using a texture analyser. Results show that compression at low pressure (0.2 MPa) is governed by the average circularity and mean diameter of the paraffin particles while compression at higher pressure seems to be governed by the uniformity of the dispersion of particle size. It helps the selection of the particle size and shape category to be used to promote candles formation and production. This study also provides a tool to assess plasticity of paraffin by using the mean yield pressure.

Correlating Single Crystal Structure, Nanomechanical, and Bulk Compaction Behavior of Febuxostat Polymorphs.

Febuxostat exhibits unprecedented solid forms with a total of 40 polymorphs and pseudopolymorphs reported. Polymorphs differ in molecular arrangement and conformation, intermolecular interactions, and various physicochemical properties, including mechanical properties. Febuxostat Form Q (FXT Q) and Form H1 (FXT H1) were investigated for crystal structure, nanomechanical parameters, and bulk deformation behavior. FXT Q showed greater compressibility, densification, and plastic deformation as compared to FXT H1 at a given compaction pressure. Lower mechanical hardness of FXT Q (0.214 GPa) as compared to FXT H1 (0.310 GPa) was found to be consistent with greater compressibility and lower mean yield pressure (38 MPa) of FXT Q. Superior compaction behavior of FXT Q was attributed to the presence of active slip systems in crystals which offered greater plastic deformation. By virtue of greater compressibility and densification, FXT Q showed higher tabletability over FXT H1. Significant correlation was found with anticipation that the preferred orientation of molecular planes into a crystal lattice translated nanomechanical parameters to a bulk compaction process. Moreover, prediction of compactibility of materials based on true density or molecular packing should be carefully evaluated, as slip-planes may cause deviation in the structure-property relationship. This study supported how molecular level crystal structure confers a bridge between particle level nanomechanical parameters and bulk level deformation behavior.