Mechanical Strength Of Tablets Research Articles

Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation.

Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also negatively affect the critical quality attributes of pharmaceutical products. Therefore, we provided a rather comprehensive evaluation of another two FDA-approved metallic stearates, sodium stearate (NaSt) and calcium stearate (CaSt), as alternative tablet lubricants. The primary objective of the present study is to comparatively evaluate the physicochemical properties and lubrication efficiency of the three metallic stearates. In addition, it was also aimed to specify the most influential factor for ranking and differentiating the lubricity of various lubricants using principal component analysis. Unit ejection force could be used herein as a simple and the most powerful parameter to evaluate the lubrication performance instead of the friction coefficient. The results suggested that CaSt, MgSt, and NaSt had similar impacts on the mechanical strength of tablets. However, CaSt exhibited insufficient lubrication effects as the formulations containing CaSt showed low pressure transmission ratios, high unit ejection forces, and high friction coefficients. In contrast, both MgSt and NaSt displayed satisfactory lubrication efficiency without negatively impacting tabletability. Notably, the lubrication performance of the formulation containing 0.5 wt% NaSt was almost identical to that of the formulation with 1 wt% MgSt, indicating that NaSt had a remarkable lubrication capability probably due to its high specific surface area. In summary, the findings of this investigation should provide practical information and feasible methodologies to readily determine the lubricity and to sensibly select alternative lubricants for pharmaceutical tablet formulations.

Prediction of the impact of lubrication on tablet compactibility

The tableting of most pharmaceutical formulations requires the addition of lubricants to reduce ejection forces, prevent tooling damage and tablet defects. The internal addition of lubricants is known to reduce tablet tensile strength, especially of mainly plastically deforming materials. To date, available models show only limited quantitative predictive accuracy for the influence of lubricant concentration on the mechanical strength of tablets. This study aims to fill this gap and present a model based on the Ryshkewitch-Duckworth equation that can estimate the compactibility profiles of lubricated formulations. Binary mixtures of different diluents (microcrystalline cellulose and lactose) were prepared with common lubricants (magnesium stearate and sodium stearyl fumarate) and subsequently tableted. The resulting compactibility profiles were fitted using the Ryshkewitch-Duckworth equation and the derived fit parameters (kb and σ0) were correlated with the lubricant concentration. Subsequently, an empirical model was established which requires a minimum of experimental data and is able to predict the tensile strength of lubricated diluent tablets. Consequently, the developed empirical model is an interesting and valuable addition to the existing multi-component compacting models available and offers the opportunity to accelerate experimentation in the development of new tablet formulations.

Prediction of quality attributes (mechanical strength, disintegration behavior and drug release) of tablets on the basis of characteristics of granules prepared by high shear wet granulation.

High shear wet granulation is commonly applied technique for commercial manufacturing of tablets. Granulation process for tablets manufacturing is generally optimized by hit and trial which involves preparation of granules under different processing parameters, compression of granules and evaluation of the resultant tablets; and adjustment is made in granulation process on the basis of characteristics of tablets. Objective of the study was to optimize the process of high shear wet granulation and prediction of characteristics of tablets on the basis of properties of granules. Atenolol granules were prepared by high shear wet granulation method, using aqueous solution of polyvinyl pyrrolidone (PVP k-30) as binder. Concentration of binder solution and granulation time were taken as process variables, both studied at three levels. Different combinations of process variables were determined by Design Expert software. Granules were evaluated for different parameters on the basis of SeDeM-ODT (Sediment Delivery Model-Oro Dispersible Tablets) expert system. Granules from all the trials were compressed using round (10.5 mm) flat faced punches at compression weight of 250 mg/tablet. Tablets were evaluated of different quality control parameters as per USP. Results showed that both the process variables had positive effect on mechanical strength of tablets and negative effect on disintegration and dissolution rate. Granule prepared with highest level of binder concentration (15%) and highest granulation time (60 sec) resulted in tablets with highest crushing strength (11.8 kg), specific crushing strength (0.328 kg/mm2), tensile strength (0.208 kg/mm2), lowest value of friability (0.19%) and highest disintegration time (10.9 min), as predicted from granules characteristics on the basis of SeDeM-ODT expert system. Drug release from Trial-13 (processed under highest level of both process parameters) was also lower than rest of the trials. It is concluded from the study that quality characteristics of tablets can be predicted from granules characteristics using SeDeM-ODT expert system. Furthermore, SeDeM-ODT expert system can also be used for optimization of the process of high shear wet granulation.

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 development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ™ 721 (fillers); Plasdone™ S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carr’s index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ™ 721), copovidone (Plasdone™ S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.

Evaluation of the Binding Property of Some Binders in Metronidazole Tablet Formulation

The binding property of five (5) commonly used binders in metronidazole granule and tablet formulations was studied. The binders studied included gelatin, polyvinylpyrrolidone (PVP), carboxymethylcellulose (CMC), maize starch and guar gum. The binders were incorporated as 5%w/w of tablet weight in each case. The granules were formulated by the wet granulation technique while the tablets were prepared by compression. The properties of granules evaluated included flow rate, angle of repose, bulk and tapped densities, Hausner’s ratio, Carr’s index and moisture content. Tablet properties studied included weight uniformity, hardness, friability, thickness and diameter, disintegration time and dissolution rate. Results indicated that granules containing guar gum or PVP possessed flow properties superior to those of other binders, while those containing gelatin possessed the least flow property. In terms of packing characteristics, granules containing CMC were better than others. The mechanical strength of tablets containing gelatin, PVP or CMC was superior to those made with either guar gum or maize starch. In terms of release of metronidazole, tablets containing PVP, gelatin or guar gum were more efficient in releasing the drug, while those made with CMC was the least. On the basis of these, good metronidazole tablets could be formulated using PVP, gelatin or guar gum. On the other hand, maize starch or CMC may not be recommended as a binder for metronidazole tablets because of high friability or poor release respectively.

Comparison of breaking tests for the characterization of the interfacial strength of bilayer tablets

The bilayer tableting technology is gaining more acceptance in the drug industry, due to its ability to improve the drug delivery strategies. It is currently assessed by the European Pharmacopoeia, that the mechanical strength of tablets can be evaluated using a diametral breaking tester. This device applies a force diametrically, and records the tablet breaking point. This approach has been used to measure the structural integrity of single layer tablets as well as bilayer (and multi-layer) tablets. The latter ones, however, have a much complex structure. Therefore, testing a bilayer tablet with the currently used breaking test methodology might not be appropriate.The aim of this work was to compare results from several tests that have been proposed to quantify the interfacial strength of bilayer tablets. The obtained results would provide an indication on which tests are appropriate to evaluate the robustness of a bilayer tablet.Bilayer tablets were fabricated using a model formulation: Microcrystalline Cellulose (MCC) for the first layer, and spray dried lactose (SDLac) as second layer.Each set of tablets were tested using the following tests: Diametral Test, Shear Test and Indentation Test.The tablets were examined before and after the breaking test using Scanning Electron Microscopy (SEM). When a bilayer tablet was subjected to shearing or indentation, it showed signs of clear delamination. Differently, using the diametral test system, the tablets showed no clear difference, before and after the testing. However, when examining each layer via SEM, it was clear that a fracture occurred in the layer made of SDLac. Thus, the diametral test is a measure of the strength of one of the two layers and therefore it is not suited to test the mechanical strength of bilayer tablets.

Theoretical considerations of the influence of polymer film coatings on the mechanical strength of tablets.

A theoretical analysis of the influence of polymer film coatings on the mechanical strength of tablets has been undertaken. Making some basic assumptions, the theory predicts that neither the thickness of the substrate nor that of the coating has any influence on which fractures first, this being solely determined by the ratio of the tensile fracture strength to the Young's modulus for the two materials. Such a finding suggests that in practice for film-coated tablets the substrate will usually fracture before the coating. Simple measurements of maximum failure loads are of little value in assessing the influence of film coating on the mechanical strength of tablets.

The characterization of the mechanical strength of tablets

The characterization of the mechanical strength of tablets

Design of aspirin formulation for rapid pain relief

Objective: Aspirin has always had excellent pain relief benefits. To reduce the gastric problems in the present study we had made an attempt to make aspirin fast dissolving tablets. Methods: Aspirin fast dissolving tablets were developed by direct compression method using Indion 254, Indion 214 and croscarmellose as superdisintegrants. Microcrystalline cellulose was used as diluent, and mannitol, as sweetening agent. The tablets were evaluated for weight variation, mechanical strength, in vitro disintegration time, wetting time and drug release characteristics. Results: Hardness and friability data indicated good mechanical strength of tablets. The results of in vitro disintegration time indicated that formulation FD3 (containing 5 mg Indion 254) as superdisintegrant was found to be suitable tablets as it showed rapid disintegration within 8 to 32 seconds. Dissolution study revealed the release rate of aspirin fast dissolving tablet and these was compared with that of marketed tablet formulation of aspirin. Conclusion: It was concluded that superdisintegrants addition technique is a useful method for preparing fast dissolving tablets by direct compression method and present study revealed that Indion 254 could produce good superdisintegrating property.

Effect of force feeder on tablet strength during compression

Mechanical strength of tablets is an important quality attribute, which depends on both formulation and process. In this study, the effect of process variables during compression on tablet tensile strength and tabletability (the ratio of tensile strength to compression pressure) was investigated using a model formulation. Increase in turret and force feeder speeds reduced tablet tensile strength and tabletability. Turret speed affected tabletability through changes in dwell time under the compression cam and the kinetics of consolidation of granules in the die cavity. The effect of force feeder was attributed to the shearing of the granulation, leading to its over-lubrication. A dimensionless equation was derived to estimate total shear imparted by the force feeder on the granulation in terms of a shear number. Scale-independence of the relationship of tabletability with the shear number was explored on a 6-station Korsch press, a 16-station Betapress, and a 35-station Korsch XL-400 press. The use of this relationship, the exact nature of which may be formulation dependent, during tablet development is expected to provide guidance to the scale-up and interchangeability of tablet presses.

Influence of temperature on the compaction of an organic powder and the mechanical strength of tablets

The purpose of this work consists in following the dependence of physical properties on the temperature during the compaction of an organic component. A special thermo-regulated die has been developed to realize uniaxial compression at different constant temperatures. This study has shown that a temperature change modifies the microstructures and the mechanical behaviour of the tablets. The measurement of the tablet porosity during the compression cycle allows us to conclude that temperature influences mainly the phenomena occurring during the isobaric stage of the compression cycle and not the ones during the pressure increase. On the other hand, during the pressure increase, the acoustical activity of the powder is reduced when temperature increases. The tensile strength of tablets realized at different temperatures was also studied and shows a maximum around 60 °C that can be explained by the SEM analysis of the microstructure of the tablets.

Effects of Lubricant Level, Method of Mixing, and Duration of Mixing on a Controlled-Release Matrix Tablet Containing Hydroxypropyl Methylcellulose

The effects of the lubricant magnesium stearate at different concentrations, mixing shear rates, and mixing times on the tablet properties and drug dissolution from controlled-release matrix tablets containing hydroxypropyl methylcellulose 2208, USP (METHOCEL® K4M Premium) have been studied. Diphenhydramine HCl and hydrochlorothiazide were chosen as the model drugs. Spray-dried hydrous lactose (Fast Flo Lactose-316®) and anhydrous dibasic calcium phosphate (A-TAB®) were chosen as the model excipient/fillers. The impact of magnesium stearate on the mechanical strength of tablets appeared to be dependent on the bonding mechanism of the components of the powder mix. Tablets containing A-TAB, which compacts via a brittle fracture mechanism, were harder and had significantly better friability patterns than those prepared using Fast Flo Lactose-316. The compaction of Fast Flo Lactose-316 appears to be a combination of brittle fracture and plastic deformation. Mixes containing lower levels of lubricant (0.2%) generated tablets that had higher crushing strengths than those with higher lubricant levels (2.0%). Drug release was impacted to the greatest extent by the solubility of the drug and excipient/filler but was only slightly affected by the level of magnesium stearate and duration of mixing.

Compressional Behaviour of an Agglomerated Cellulose Powder

The ability of an agglomerated cellulose powder to total and plastic deformation was evaluated and compared with those of Avicel PH 101, Emcocel and an experimental depolymerized cellulose powder. The elastic recovery of compressed cellulose tablets was also measured. The effects of deformation of the material during the tableting process and recovery of tablet after maximum compression on the mechanical strength of tablets were also discussed.The apparent net work done into tablets during compression as well as the yield pressures to total and plastic deformation, determined from the Heckel treatment, showed no great differences between the agglomerated cellulose powder and the other cellulose powders. Thus all the cellulose materials studied had rather similar ability to total, i.e. elastic and plastic, deformation and to permanent, i.e. pure plastic, deformation. The obvious fragmentation of the agglomerated cellulose powder already at low compressional pressure, however, seemed to be advantageous for the formation of strong compacts.Both rapid and total elastic recovery of compressed cellulose tablets showed clear differences between the cellulose materials and these differences correlated with the previously measured strength of cellulose tablets. The agglomerated cellulose powder had the smallest tendency to both kind of elastic recoveries of tablets. Obviously, due to the large interparticle contact areas, the ability of this material to establish more bonds between adjacent particles during compression was greater than those of other celluloses. The elastic recovery was greatest for depolymerized cellulose tablets indicating the poorest binding ability of the particles of this material.

Compressional Behaviour of an Agglomerated Cellulose Powder

AbstractThe ability of an agglomerated cellulose powder to total and plastic deformation was evaluated and compared with those of Avicel PH 101, Emcocel and an experimental depolymerized cellulose powder. The elastic recovely of compressed cellulose tablets was also measured. The effects of deformation of the material during the tableting process and recovery of tablet after maximum compression on the mechanical strength of tablets were also discussed.The apparent net work done into tablets during compression as well as the yield pressures to total and plastic deformation, determined from the Heckel treatment, showed no great differences between the agglomerated cellulose powder and the other cellulose powders. Thus all the cellulose materials studied had rather similar ability to total, i.e. elastic and plastic, deformation and to permanent, i.e. pure plastic, deformation. The obvious fragmentation of the agglomerated cellulose powder already at low compressional pressure, however, seemed to be advantage...

Studies on direct compression of tablets II. The influence of the particle size of a dry binder on the mechanical strength of tablets

Tablets of free-flowing lactose, paracetamol, ascorbic acid and sodium chloride were compressed in an instrumented single-punch press. Five size fractions of methyl cellulose powder were added as binder. Increasing amounts of methyl cellulose increased the tablet strength of all materials. Small additions of coarse binder reduced the strength of sodium chloride tablets, however. The particle size of the binder was very important for the effect and fine fractions were considerably more effective. The effect of the particle size was smallest in lactose tablets, possibly due to the pronounced fragmentation of this material during compaction. Sodium chloride which did not fragment during tabletting was most affected by particle size variation of the binder. For paracetamol and ascorbic acid the tablet strength was directly related to the degree of surface coating obtained by the binder.

The Influence of Magnesium Stearate on time Dependent Strength Changes in Tablets

Changes in the mechanical strength of tablets with time are well documented. Sodium chloride tablets increase in strength by over 100% in the first hour after manufacture. It is shown that when mixed with magnesium stearate, this strength change does not occur. Results are also presented for lactose tablets, and possible mechanisms are discussed.

Formulation and Evaluation of Oro Dispersible Tablets of Ondansetron Hydrochloride by Direct Compression using Superdisintegrants

The objective of the present investigation was to prepare oro dispersible tablets of ondansetron hydrochloride, because of its application in emesis condition, fast onset of action and avoidance of water is highly desirable. Tablets were prepared by direct compression using sodium starch glycolate and croscarmellose as superdisintegrants, as the combination of these two agents gives better disintegration of the tablet. Microcrystalline cellulose was used as diluent and mannitol, mint flavor, sodium saccharine to enhance the organoleptic properties of tablets. The tablets were evaluated for weight variation, mechanical strength, in vitro disintegration time, in vivo disintegration time, wetting time, and drug release characteristics. Hardness and friability data indicated good mechanical strength of tablets. The results of in vitro disintegration time and in vivo disintegration time indicated that the tablets dispersed rapidly in mouth within 3 to 5 seconds. Dissolution study revealed faster release rate of ondansetron hydrochloride from the tablets as compared to pure drug and marketed conventional tablet formulation of ondansetron hydrochloride. It was concluded that superdisintegrants addition technique is a useful method for preparing oro dispersible tablets by direct compression method