Mechanical Properties Of Tablets Research Articles

A Comparative Assessment of Cocrystal and Amorphous Solid Dispersion Printlets Developed by Hot Melt Extrusion Paired Fused Deposition Modeling for Dissolution Enhancement and Stability of Ibuprofen.

The primary focus of the research is to study the role of cocrystal and amorphous solid dispersion approaches for enhancing solubility and preserving the stability of a poorly soluble drug, i.e., ibuprofen (IBP). First, the solvent-assisted grinding approach determined the optimum molar ratio of the drug and the coformer (nicotinamide (NIC)). Later, the polymeric filaments of cocrystals and amorphous solid dispersions were developed using the hot melt extrusion (HME) process, and the printlets were fabricated using the fused deposition modeling (FDM) additive manufacturing process. In addition, the obtained filaments were also milled and compressed into tablets as reference samples. The formation of cocrystals and amorphous solid dispersions was evaluated and confirmed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD) analysis. The drug release profiles of 3D printlets with 50% infill were found to be faster and are in line with the release profiles of compressed tablets. In addition, the 3D-printed cocrystal formulation was stable for 6months at accelerated conditions. However, the 3D printlets of amorphous solid dispersions and compressed tablets failed to retain stability attributed to the recrystallization of the drug and loss in tablet mechanical properties. This shows the suitability of a cocrystal platform as a novel approach for developing stable formulations of poorly soluble drug substances over amorphous solid dispersions.

Influence of Process Parameters and Particle Size Distribution on Mechanical Properties of Tablets

AbstractThe influence of the particle size distribution of maltodextrin powders with a dextrose equivalent level of 29 as well as two tableting process variables, namely the compression pressure and the dwell time, on the tensile strength, porosity, and pore size distribution of the final tablet was studied. The mechanical strength and porosity of the tablets are assessed in relation to the powder and process parameters. Regarding the process parameter, it was show that the compaction pressure clearly has a more pronounced influence on the tablet porosity and mechanical strength compared to the influence of the dwell time in the range of the study. As a result, the study offers a better understanding of how the properties of a tablet are influenced by the inter‐correlation of powder characteristics and tableting parameters. Therefore, the shelf‐life studies and tablet downstream processing as well as drug product development will benefit greatly from this work.

Faster to First-time-in-Human: Prediction of the liquid solid ratio for continuous wet granulation

In early development, when active pharmaceutical ingredient (API) is in short supply, it would be beneficial to reduce the number of experiments by predicting a suitable L/S ratio before starting the product development. The aim of the study was to decrease development time and the amount of API needed for the process development of high drug load formulations for continuous twin-screw wet granulation (TSWG). Mixer torque rheometry was used as a pre-formulation tool to predict the suitable L/S ratios for granulation experiments. Three different values that were based on the MTR curves, were determined and assessed for their ability to predict the suitable L/S ratio for TSWG. Three APIs (allopurinol, paracetamol and metformin HCl) were used as model substances in high drug load formulations containing 60% drug substance. The MCC-mannitol ratio was varied to assess the optimal composition for the high-dose formulations. The API solubility affected the mixer torque rheometer (MTR) curves and the optimum L/S ratio for TSWG. The highly soluble metformin needed a much lower L/S ratio compared with allopurinol and paracetamol. A design space was determined for each API based on granule flowability and tablet tensile strength. The flowability of the granules and tensile strength of the tablets improved with an increasing L/S ratio. The MCC-mannitol filler ratio had a significant effect on tabletability for paracetamol and metformin, and these APIs having poor compaction properties needed higher MCC ratios to achieve the 2 MPa limit. The MCC-mannitol ratio had no effect on the granule flow properties. Instead, API properties had the largest influence on both granule flow properties and tensile strength. Based on this study, both the L/S ratio and MCC-mannitol ratio are crucial in controlling the critical quality attributes in high drug load formulations processed by TSWG. The optimum flow and tablet mechanical properties were achieved when using 75:25 MCC-mannitol ratio. Both start of the slope and 2/3 of the L/S ratio at the maximum torque in MTR provided a solid guideline to aim for in a TSWG experiment.

Investigation on the impact of different proportions of components in formulations on stability of a moisture sensitive drug

Physicochemical and mechanical properties of tablets are largely dictated by formulation compositions. Different excipients possess different tableting and moisture sorption behaviors. Therefore, this study was designed to elucidate the relative influence of the proportion of components in formulations on tablet properties. Acetylsalicylic acid (ASA) tablets containing different proportions of starch, microcrystalline cellulose (MCC) and calcium hydrogen phosphate dihydrate (DCP) were prepared. The excipients were evaluated for their moisture sorption properties. Mechanical strength of the tablets was determined alongside with ASA stability, by storing the tablets at 75% RH, 25 °C. The stability study showed the importance of drug loading level on its stability. For a fixed ASA proportion, formulations with more starch were able to absorb more moisture and possessed larger areas of hysteresis loop in their moisture sorption isotherms. The presence of starch contributed positively to ASA stability although increasing proportions of starch compromised the tablet mechanical properties. Contrastingly, MCC produced mechanically stronger tablets as its plastically deforming and fibrous properties contributed to a good structural network. The findings provide a deeper understanding of the dichotomous effect by the proportion of components in formulations containing a moisture sensitive drug on drug stability and mechanical strength of the resultant tablets.

Formulation and antianaemic evaluation of the tablets containing Telfairia occidentalis aqueous leaf extract

<p class="MsoNormal">The efficacy of plants in the treatment of various diseaseshas led to the development of presentable and acceptable herbal formulations.This study evaluated the suitability of different binders in the formulation ofdried aqueous leaf extract of&nbsp;Telfairia occidentalis&nbsp;(TOLE) tablets.Granules were prepared by wet granulation using polyvinyl pyrrolidone (PVP),corn starch (CS) and gelatin (GEL)&nbsp;at 5 %w/v&nbsp;and then compressed intotablets.&nbsp;Flow properties of granules; angle of repose, Hausner ratio andCarr’s index was determined, mechanical properties of tablets; hardness,friability and disintegration time were evaluated and anti-anaemic assessmentof the optimized tablet was carried out using standard methods. Results showthat TOLE and the granule formulations possessed good flow properties. Tablethardness was 5.22, 5.18, 4.40 kgF for GEL&gt;CS&gt;PVP respectively; friabilityvalues were 0.00, 0.20 and 0.34 % respectively. Tablets disintegrated between28 and &gt; 60 min; only those prepared with PVP disintegrated within theofficial specified time. The optimized tablets were comparable with TOLE inimproving haematological indices of mice.&nbsp;All the bindersproduced&nbsp;robust&nbsp;tablets but PVP is considered the mostsuitable,&nbsp;in vivo&nbsp;study revealed TOLE retained its activity in theformulated tablet suggesting the formulation can be used as an oralanti-anaemic supplement.&nbsp;<o:p></o:p>

Compaction behaviour of mannitol-cocoa powder mixtures and their resulting tablet strength and disintegration characteristics

Cocoa powder is an important ingredient in the confectionery industry and, mannitol is an alternative sugar alcohol. In this work, mannitol powder was mixed with cocoa powder and compacted into tablet form via the uniaxial die compaction process. The frictional, compaction, tablet mechanical and disintegration properties were studied due to their importance in characterizing the behaviour of the tablets during processing and its final product characteristics at varying mannitol contents. The composition of mannitol in the mannitol-cocoa tablet varied at 95% w/w, 50% w/w and 5% w/w, while pure 100% w/w mannitol and cocoa tablets were set as controls. The compaction pressures used in making the tablets varied at 37.67 MPa, 75.34 MPa, 113.01 MPa, 150.68 MPa and 188.35 MPa. The compaction behaviour of the powder during the compaction process was evaluated using the plastic work and the maximum ejection stress values. The tablet strength was determined using the tensile strength method and tablet disintegration study was also conducted. The results showed that the increase in the compaction pressures increased the plastic work, maximum ejection pressure, tablet strength and also its disintegration time. The tablet formed having 95% w/w mannitol composition exhibited the highest plastic work value of 10.32±0.01 J, highest maximum ejection pressure value of 4.4±0.06 MPa, highest tensile strength value of 1.06±0.04 MPa and shortest disintegration time of 171±51 s amongst the three different mannitol compositions studied. Meanwhile, the effects of mannitol composition in the tablet on these observed responses were also dependent upon the compaction pressures used during tablet formation. In conclusion, the addition of mannitol improved the tablet strength and shorten the disintegration time in the experimental range employed in this study.

Co-Processed Particles: An Approach to Transform Poor Tableting Properties

The role of co-processing in improving tablet mechanical properties was investigated in this work. Gabapentin was used as the model compound owing to its poor tableting properties such as low tensile strength, strain rate sensitivity, high ejection force, and tablet capping. Gabapentin was blended with hydroxypropyl methylcellulose (Methocel®) in a high shear mixer to obtain an interactive mixture consisting of finer hydroxypropyl methylcellulose particles adsorbed onto the surface of larger gabapentin particles. Interactive mixture containing <1% by weight Methocel® was compressed on a material testing system (Instron®) to evaluate tablet mechanical properties. This co-processed gabapentin demonstrated improvement in tablet tensile strength and strain rate sensitivity which was attributed to improved particle bonding. In comparison, Methocel® 10% (w/w) low-shear mixture demonstrated strain rate sensitivity and lower tensile strength. Furthermore, Methocel® coating on gabapentin particles provided lubricity and decreased die-wall friction resulting in reduced tablet capping. This methodology has applications in improving mechanical properties of poorly compressible high-dose drugs without the use of high level of excipients. Furthermore, reduction in die-wall friction through particle surface coating could prove beneficial for formulations prone to overlubrication and slow dissolution owing to magnesium stearate.

Effect of intra- and extragranular addition of highly porous tribasic calcium phosphate on properties of immediate release acyclovir formulation – Comparison with commercial tablets using compendial and biorelevant dissolution methods

Immediate release, compositionally proportional formulations of acyclovir comprising porous tribasic calcium phosphate were developed and compared with commercial tablets. Comparison of the dissolution behavior was carried out using a compendial method, as well as with the help of a biorelevant dissolution stress test device, which simulates physiological mechanical stress occurring in the gastrointestinal tract. The results showed that the way how tribasic calcium phosphate is used (intra- or extragranular) had an impact on the mechanical properties of tablets as well as their dissolution performance. The dissolution rate of acyclovir from the developed formulations was fast and similar to marketed formulations.

Matrix Tablets for Controlled Release of Drugs Incorporated Using Capillary Absorption.

Cost and time effectiveness make direct tableting still the favored method for tablet production. Among its most noticeable limitations in application is the non-uniformity (and/or inhomogeneities) in the contents of the resulting tablets, possibly leading to inconsistencies in required tablet properties. The efficiency of direct tableting is mostly affected by surface properties of the components to be tableted, which govern the final tablet mechanical and chemical properties and can influence the liquid capillary rise that the tablets exhibit after ingestion. By using capillary rise as a driving force, we developed a simple, yet powerful procedure for filling blank tablets with a repeatable drug amount. Blank tablets were prepared by direct compression of the excipient and filled with an organic solution of hydrochlorothiazide. Tablets were characterized regarding their structure and morphology, while their applicability was monitored using in vitro drug release studies. By utilizing the mentioned filling of blank tablets, we were able to incorporate the desired dose of the drug inside while maintaining the tablets initial mechanical properties. Moreover, most of the drug was incorporated in the tablet pores and the rest was homogeneously distributed over the tablet surface in the form of small particles, by which we also eliminated content non-uniformity (homogenous drug distribution through the tablet). To sum up, we not only developed a cheap, simple, and reproducible variation of direct tableting, but were also able to eliminate some of its biggest disadvantages (e.g., segregation of components, leading to inhomogeneities in contents, and incompatibility between different base ingredients due to their different surface properties). All mentioned make the proposed approach highly interesting for future use, especially in potential therapy individualization.

Influence of punch geometry (head-flat diameter) and tooling type (‘B’ or ‘D’) on the physical–mechanical properties of formulation tablets

The presented study assessed the influence of punch geometry (head-flat [HF] diameter) and tooling type (‘B’ or ‘D’) on the physical–mechanical properties of tablets prepared by direct-compression of two guaifenesin (25% or 40% w/w) formulations. Tablets of both formulations were prepared on instrumented, single-layer, rotary tablet press using 10 mm, flat-faced, ‘B’ or ‘D’-type tooling with different HF diameters, and compression forces (CF) ranging from 5 to 25 kN with 5 kN increments. The tablets were evaluated for dimensions, weight variation, tensile strength (TS), friability, and capping index. In general, tablets prepared using ‘D’ tooling showed a significantly (p < 0.05) higher TS compared to those prepared using ‘B’ tooling, likely due to higher dwell-times associated with ‘D’ tooling. Formulations containing 25% w/w guaifenesin showed a significantly (p < 0.05) higher TS compared to those containing 40% w/w guaifenesin, at given compression CF, punch geometry, or tooling type. This could be due to the higher ratio of Prosolv® SMCC contributing to the compressibility. For both formulations compressed using ‘B’ tooling, differences in TS profiles were observed between different HF tooling. The TS of these tablets increased significantly with increasing HF diameter. For formulations compressed using ‘D’ tooling, this trend was observed only up to a CF of 15 kN, beyond which the TS plateaued, possibly due to work-hardening of the formulation at higher CF. These formulations also exhibited capping at CF above 15 kN and with higher HF diameters. The study showed a significant influence of punch geometry and tooling type on the physical properties of tablets.

Transient Temperature Monitoring of Pharmaceutical Tablets During Compaction Using Infrared Thermography.

Manufacturing of pharmaceutical tablets from powders is always accompanied by the conversion of irreversible mechanical work of compaction into heat. The heat is generated due to friction between powder particles, particles and the die wall, plastic deformation of particles, bonding, and other irreversible processes. The resulting temperature increase potentially might have significant effects on a tablet's mechanical properties, disintegration time, and drug release. In the present work, we show that using infrared thermography as a nondestructive and noncontact process analytical technology (PAT) tool to measure the tablet's rate of cooling, in contrast to the temperature evolution, can be directly related to the tablet's thermal diffusivity. Results show the potential capabilities of this technique to discriminate and toward predicting tensile strength of tablets between same formulations produced at same compaction force but experienced different process shear conditions. Correlation of the tablet's tensile strength, relative density, and rate of cooling at regular regime with respect to different process shear is also discussed.

Evaluation of the mechanical properties of tablets obtained from the lyophilized avocado pulp

The objective of this work was to evaluate the mechanical properties of tablets prepared from lyophilized avocado pulp using thickener in their formulation. Three concentrations of the thickener, carboxymethylcellulose (CMC) in the avocado/milk/sugar mixture were tested, where the treatment (T1) contained 0.109%, (T2) with 0.218% and the third (T3) with 0.327%. It was observed that the treatments T1, T2 and T3 had hardness (N) of 92.16, 118.01 and 157.42, respectively. The work (mJ) used for penetration of the probe was 191.06, 216.98 and 346.55 for T1, T2 and T3, respectively. As the concentration of the thickener in the tablet formulation was increased, the hardness and workability were also increased.

Dependence of Friability on Tablet Mechanical Properties and a Predictive Approach for Binary Mixtures

To systematically assess the dependence of friability on tablet mechanical properties, compaction pressure, and tablet porosity. Several common excipients and their mixtures exhibiting diverse mechanical properties were analyzed. Tablet elastic modulus, hardness, brittleness, porosity, and tensile strength were determined using standard techniques and then were correlated to tablet friability both individually and as a group to derive a universal model. Viscoelastic starch exhibits the highest friability followed by brittle excipients (mannitol, DCPA, and LM) and then ductile excipients (HPC and MCC). A reasonably accurate model for predicting pharmaceutically relevant range of friability, up to 3%, of binary mixtures is presented based on friability of individual components. In addition, a multivariate model between friability and different mechanical parameters was developed, based on which the weight loss propensity of tablets may be predicted. The experimental findings and predictive model are useful for expedited development and optimization of tablet formulation using a minimum amount of API.

Mechanistic modelling of industrial-scale roller compactor ‘Freund TF-MINI model’

A pharmaceutical roller compaction process was modelled using the Johanson powder mechanics model, which may be employed to achieve desired process performance. Mathematical modelling of the compaction of microcrystalline cellulose (PH102) was used to determine optimal process conditions for an industrial scale roll compactor (Freund, Model TF-MINI). The critical process parameters investigated were screw speed and roll pressure, while the rolls were kept at constant speed and the roll gap as variable. The roll-compacted ribbon density was considered the quality attribute of interest, as it is directly linked to the granule properties, particle size distribution and tablet mechanical properties. Experimental process data were used for model calibration and validation. This was followed by utilisation of the predictive capability of the model to achieve desired process performance of the compactor. The model findings indicated that the developed mechanistic model for the roller compactor can provide a design space to correlate the process parameters and materials properties to the critical quality attributes of granules which would be useful for implementation of Quality-by-Design paradigm in pharmaceutical manufacturing.

Influence of the Punch Head Design on the Physical Quality of Tablets Produced in a Rotary Press

This study aims to investigate the influence of tablet punch head design on compaction and the resultant tablet mechanical properties. Tablets were prepared using flat-face punches with different head flat and head radius configurations, on a rotary tablet press with compression rolls of different diameters. The results showed that tablets produced using punches with head flats consistently displayed higher tensile strengths and lower capping tendencies. Exclusion of the head flat in the punch head geometry caused the compacts to undergo a state of continual deformation during the compaction cycle, possibly with increasing elasticity without the opportunity for more prolonged stress relaxation. Extension of head flat diameter produced small increments in dwell time and this could bring about significant improvements to the tablet mechanical quality. Changes to the punch head radius were found only to affect the compression profiles marginally, but this only produced insignificant differences in the tablet mechanical properties. A smaller compression roll allowed greater plastic flow during the dwell phase, but this was insufficient to effectively counteract the adverse effects due to increased strain rate during the consolidation phase, leading to deterioration of tablet mechanical quality.

Note on the Use of Diametrical Compression to Determine Tablet Tensile Strength

The diametrical compression (DC) test, as defined in United States Pharmacopeia <1217> and in American Society for Testing and Materials testing standard D 3967, has been used extensively to derive the tensile strength (TS) of pharmaceutical tablets from the measured breaking force. DC-derived TSs provide a good approach to measuring the consistency of tablet mechanical properties from one batch to the next. For these quality control type applications, method precision is required, but accuracy is not. In addition, DC has been used to calibrate parameters of the Druker Prager Cap model, a yield criterion expressing the failure of a powder compact under arbitrary 3D loading conditions. For this application, the DC method must not only provide suitable precision but also provide accuracy. In this work, we explore the accuracy of the DC method by comparing TS results to those of the 3-point bend test method (also defined in United States Pharmacopeia <1217>). We conclude that the true TS of a powder compact is approximately double the DC-derived value. Although historical literature assumes that tablets fracture under tension along the centerline of the tablet, analysis of the stress state suggests that tablets are likely to fracture under shear. The impact of this ∼50% error should be considered when accuracy of the TS result is required.

To Study Capping or Lamination Tendency of Tablets Through Evaluation of Powder Rheological Properties and Tablet Mechanical Properties of Directly Compressible Blends.

Air entrapment efficiency of the powders is one of the main factors leading to occurrence of capping or lamination tendency of tablets manufactured from the directly compressible powder blends. The purpose of the current research was to study this underlying cause leading to occurrence of capping or lamination of tablets through evaluation of powder rheological properties. Powder blends were prepared by addition of 0% w/w to 100% w/w of individual active pharmaceutical ingredient (API) [two model API: acetaminophen (APAP) and ibuprofen (IBU)] with microcrystalline cellulose without and with 0.5% w/w Magnesium Stearate as lubricant. Powder rheological properties were analyzed using FT4 Powder Rheometer for dynamic, bulk, and shear properties. Tablet mechanical properties of the respective blends were studied by determining the ability of the material to form tablet of specific strength under applied compaction pressure through tabletability profile. The results showed that powder rheometer distinguished the powder blends based on their ability to relieve entrapped air along with the distinctive flow characteristics. Powder blend prepared with increasing addition of APAP displayed low powder permeability as compared to IBU blends with better powder permeability, compressibility and flow characteristics. Also, lubrication of the APAP blends did not ease their ability to relieve air. Tabletability profiles revealed the potential occurrence of capping or lamination in tablets prepared from the powder blends with high APAP content. This study can help scientist to understand tableting performance at the early-developmental stages and can avoid occurrence capping and lamination of tablets.

Dependence of tablet brittleness on tensile strength and porosity

An analysis of data collected from 25 sets of diverse pharmaceutical powders has identified that an exponential growth function satisfactorily describes the relationship between tablet brittleness and tablet porosity while a power law function well describes the relationship between tablet brittleness and tensile strength. These equations have the potential to facilitate better characterization of tablet mechanical properties and to guide the design and optimization of pharmaceutical tablet products.

Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrocloride sustained release matrix tablets

This study investigates using of high molecular weight polyethylene oxide (PEO WSR Coagulant) for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 minutes were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 minutes, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline celullose) exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinised starch (Strach 1500).

Comparison of drug release and mechanical properties of tramadol-hydrochloride matrix tablets prepared with selected hydrophilic polymers

This study investigates using of high molecular weight hydrophilic polymers, hypromellose and hydroxypropylcellulose, for the preparation of sustained release matrix tablets containing high dose, highly soluble drug, tramadol HCl. Proportion of polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in the tablet and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Tensile strength was used as indicator of mechanical properties of the tablets. Experiments were performed with utilization of compaction simulator as a device which simulates compaction profiles of large scale rotary tablet presses. In formulations with both polymers proportion of tramadol HCl was the most critical formulation parameter wherein increasing of the tramadol HCl proportion increased its release rate in early stages of drug release. Regarding the tablet mechanical characteristics, the influence of the filler type has the most pronounced effect in formulations with both polymers. Higher tensile strengths were obtained with Avicel PH 102 as filler in formulations with both HPMC and HPC.