Brittle Fracture Index Values Research Articles

The Impact of Hot Melt Extrusion and Spray Drying on Mechanical Properties and Tableting Indices of Materials Used in Pharmaceutical Development

The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd ) were determined along with Hiestand indices using compacts prepared at a solid fraction of ∼0.85. HPMCAS and copovidone exhibited lower Hd , lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd . Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId ) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development.

Fundamental properties of metronidazole formulations in relation to tableting.

A study has been made of the effects of polyvinylpyrrolidone, gelatin and methylcellulose binding agents on the fundamental and tableting properties of a metronidazole-lactose-starch formulation. A material constant, alpha, was derived from the measured values of tensile strength of the materials. The values of alpha for the formulations are lower than that for metronidazole and depend on the nature and concentration of binder present. In terms of tableting properties, alpha supplements the information obtained from the ratios of elastic recovery to plastic compression (ER/PC) and from the brittle fracture index values (BFI) of the materials, although its influence appears to be limited at low values of ER/PC.

Evaluation of Khaya Gum as a Binder in a Paracetamol Tablet Formulation

A study of the comparative effects of khaya gum and two standard binding agents, polyvinylpyrrolidone (PVP) and gelatin, on the compressional characteristics of a paracetamol tablet formulation and on the mechanical properties of the tablets was made. Compressional characteristics were analysed using density measurements and the Heckel and Kawakita plots. The loose initial relative density (D0) of the formulation increased with increased binder concentration while the packed initial relative density (Di) decreased. The degree of densification achieved for the formulation at low pressures (Db) and at both zero and low pressures (Da) decreased with increased binder concentration. The mean yield pressure (Py) for the formulation decreased with increase in binder concentration, with formulations containing khaya gum having the lowest Py values and those containing gelatin exhibiting the highest values. Another pressure term, Pk (an inverse measure of plasticity) decreased with increase in binder concentration, with formulations containing PVP having the lowest Pk values and those containing khaya gum and gelatin having similar Pk values. The tensile strength (T) of the paracetamol tablets increased with increase in binder concentration while the brittle fracture index (BFI) decreased. Tablets containing PVP exhibited the highest T values while those containing khaya gum exhibited the lowest values. The same trend was obtained for the BFI values with tablets containing khaya gum exhibiting the lowest values. The results suggest that khaya gum could be useful as a binding agent for particular tablet formulations.

Brittle fracture index (BFI) as a tool in the classification, grouping, and ranking of some binders used in tablet formulation: Lactose tablets

This work aims at classifying, grouping and ranking binders based on their abilities to ameliorate capping and lamination in lactose tablets using BFI as a tool. Binders from different “families” (for example, starches, celluloses, natural gums, and synthetic gums) were employed via the wet granulation process at concentrations ranging from 1.0 - 12.5% w/w to formulate tablets with and without centre holes at a compression pressure of 7.5 arbitrary units. The tablets dimensions were determined in triplicates, with the resulting values used to calculate their tensile strengths. The means of the tensile strengths were then used to calculate BFI. Analyses of the results were done using Friedman’s test and regression analysis. The analyses revealed that BFI was a useful tool in grouping binders based on their abilities to ameliorate capping and lamination in lactose tablets. It was also useful in ranking the binders based on their levels of effectiveness in solving the problem; however, it was not useful in classifying the binders based on nature or origin since no particular “family” occupied a unique range of BFI values in the task of ameliorating capping and lamination in lactose tablets. The findings from this work will be very helpful to pharmaceutical formulators since the selection of the best and most economic alternative binder(s) from an array of available binders to produce tablets with little or no incidence of capping and lamination will be greatly enabled by them.

Comparative study of some mechanical and release properties of paracetamol tablets formulated with cashew tree gum, povidone and gelatin as binders

The mechanical and release properties of paracetamol tablets formulated with cashew gum (CAG), povidone (PVP) and gelatin (GEL) as binders were studied and compared. The parameters studied were tensile strength (TS), brittle fracture index (BFI), friability (F), disintegration time (DT) and percentage drug released (PDR). Results showed that the TS and BFI values of tablets formulated with CAG were the lowest at all binder concentrations. The friabilities of all formulations were within accepted limits (<1.0%). Disintegration times were longest for GEL formulated tablets and least for PVP formulated ones. At binder concentrations of 1.0 – 3.0% (w/w) CAG released the highest cumulative amount of drug in 30 min; from 4.0 – 5.0% (w/w) cumulative amount released became highest for PVP formulated tablets. GEL formulated tablets generally released the least amount. CAG gum therefore having imparted better BFI than PVP or GEL, and does not hinder drug release is strongly recommended as an alternative to the more expensive PVP or GEL for immediate release tablet formulations. Key words: Cashew gum, povidone, gelatin, binder, mechanical, release properties of paracetamol tablets.

Evaluation of the physical and mechanical properties of high drug load formulations: Wet granulation vs. novel foam granulation

The purpose of this study was to evaluate the influences of intrinsic drug mechanical properties and different granulation binder delivery processes on the physical and mechanical properties of high drug load granulations after wet granulation. Formulations (80% w/w) of acetaminophen (APAP), metformin and aspirin, which are brittle, viscoelastic, and ductile, respectively; were granulated by high-shear wet granulation. Two modes of binder delivery for wet granulation, either conventional or binder foam, were investigated. Particle size, surface area and pore size of the granulations were characterized. Compacts were prepared at a solid fraction of 0.9 under tri-axial decompression and Hiestand indices (worst-case bonding index (BI w) and brittle fracture index (BFI)) of the compacts were determined. APAP formulations exhibited the smallest geometric mean particle sizes ( d g) and showed only slight differences in d g values between the two granulation processes. Binder delivery mode affected mechanical properties of the granulated model drugs differently. Foam granulation appeared to enhance the granule plasticity for APAP while aspirin showed a mixed deformation mechanism based on both its high BI w and high BFI values. The higher BI w value for aspirin after foam granulation may be attributed to improved binder distribution among particles during granulation. On the other hand, conventional wet granulation improved the plasticity of metformin as measured by the higher BI w and lower BFI values. Therefore, conventional wet granulation process conferred advantages in manufacturability and product quality for metformin; as compared to foam granulation which did not enhance plasticity for metformin. Based on this study, a wet granulation process can be selected based on knowledge of the intrinsic drug mechanical properties.

Comparative study of some mechanical and release properties of paracetamol tablets formulated with cashew tree gum, povidone and gelatin as binders

The mechanical and release properties of paracetamol tablets formulated with cashew gum (CAG), povidone (PVP) and gelatin (GEL) as binders were studied and compared. The parameters studied were tensile strength (TS), brittle fracture index (BFI), friability (F), disintegration time (DT) and percentage drug released (PDR). Results showed that the TS and BFI values of tablets formulated with CAG were the lowest at all binder concentrations. The friabilities of all formulations were within accepted limits (

Relationship Between Slugging Pressure and Brittle Fracture Tendency – A Case Study for Aspirin Tablets

Objective – Slugging is a pre-compression technique for the dry granulation of hydrolysable drugs (e.g. aspirin). The study was carried out to relate the slugging load to the hardness of the granules and the brittle fracture tendency of the final (recompressed) tablets. Method – Varying compression load were applied to aspirin powder to form slugs, which were subsequently broken down to form granules. These were recompressed to give the final tablets. The hardness of the slugs was determined and taken as measure of the hardness of the resulting granules. The following tableting parameters were measured for the final tablets - tensile strength (T), packing fraction (Pf) and the brittle fracture index (BFI). Results - A high slugging load was associated with the formation of hard slugs and hence hard granules. Upon recompression the hardest granules formed the hardest tablets (T = 3.29MN m-2) while the softest granules formed the softest tablets (T=1.09MN m-2). In turn, the hardest tablets displayed the highest brittle fracture tendency (BFI = 0.59) compared with the softest tablets (BFI= 0.21). A positive linear correlation existed between tablet hardness (T) and BFI values (r = 0.98). Keywords: Slugging pressure, aspirin granules, tablet tensile strength, brittle fracture index > Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 483-487

Influence of some starch binders on the brittle fracture tendency of paracetamol tablets

The study was carried out to compare the binder effects of cassava and cocoyam starch with that of maize starch BP. The parameters investigated were the brittle fracture index (BFI), the tablet packing fraction (Pf), and tensile strength (T). Mucilages of the starches of varying concentrations; 15, 20, and 25% (w/v) were formed; their viscosities were determined and used to form paracetamol granules by wet-massing. The granules were compressed at different compression loads (arbitrary units on the load scale; 8, 9 and 9.5). At all given compression loads and at all binder concentration, cassava starch mucilages binder produced the hardest and most compact tablets with the least tendency to brittle fracture compared with cocoyam or maize starch mucilage. For instance, the BFI values at the compression load, 8 were 0.13 (tablets formed with cassava starch mucilage 20% w/v) 0.18 (tablets formed with cocoyam starch mucilage 20% w/v) and 0.35 (tablets formed with maize starch mucilage 20% w/v). Increase in compression load (8 to 9.5) increased the BFI of these tablets while an increase in binder concentration generally caused a decrease in BFI of these tablets. This decrease was less marked at higher compression load. The results indicate that cassava starch mucilage which was the most viscous, displayed the highest potential for ameliorating brittle fracture during manufacture of paracetamol tablets.

Influence of some starch binders on the brittle fracture tendency of paracetamol tablets

The study was carried out to compare the binder effects of cassava and cocoyam starch with that of maize starch BP. The parameters investigated were the brittle fracture index (BFI), the tablet packing fraction (Pf), and tensile strength (T). Mucilages of the starches of varying concentrations; 15, 20, and 25% (w/v) were formed; their viscosities were determined and used to form paracetamol granules by wet-massing. The granules were compressed at different compression loads (arbitrary units on the load scale; 8, 9 and 9.5). At all given compression loads and at all binder concentration, cassava starch mucilages binder produced the hardest and most compact tablets with the least tendency to brittle fracture compared with cocoyam or maize starch mucilage. For instance, the BFI values at the compression load, 8 were 0.13 (tablets formed with cassava starch mucilage 20% w/v) 0.18 (tablets formed with cocoyam starch mucilage 20% w/v) and 0.35 (tablets formed with maize starch mucilage 20% w/v). Increase in compression load (8 to 9.5) increased the BFI of these tablets while an increase in binder concentration generally caused a decrease in BFI of these tablets. This decrease was less marked at higher compression load. The results indicate that cassava starch mucilage which was the most viscous, displayed the highest potential for ameliorating brittle fracture during manufacture of paracetamol tablets. Key words: Cassava, cocoyam, maize starch, binder effect, tensile strength, brittle fracture index, tableting.

Evaluation of Dika Nut Mucilage (Irvingia gabonensis) as Binding Agent in Metronidazole Tablet Formulations

Dika nut mucilage obtained from the nuts of Irvingia gabonensis (O'Rorke) Bail (family Irvingiaceae) has been evaluated as a binding agent in metronidazole tablet formulations in comparison with gelatin BP. The compressional properties of metronidazole formulations were analyzed using density measurements and the Heckel equations as assessment parameters, whereas the mechanical properties of the tablets were assessed using the tensile strength (T), brittle fracture index (BFI), and the friability of the tablets. The drug release properties of the tablets were assessed using disintegration and dissolution times of the tablets. The results obtained indicate that formulations containing dika nut mucilage as binding agent show faster onset of plastic deformation under compression pressure than those containing gelatin. The tensile strength of the tablets increased with increase in concentration of the binding agents, whereas the BFI and friability values decreased. Furthermore, tablets containing dika nut mucilage generally showed lower tensile strength but higher brittleness and friability than those containing gelatin. The results also showed that tablets containing dika nut mucilage generally showed higher disintegration and dissolution times than those containing gelatin BP. The results suggest that dika nut mucilage could be useful in achieving various tablet strength and drug release properties.

Anomalous effect of compression pressure on the brittle fracture tendency of α-cellulose tablets

The effect of varying the compression pressure on the brittle fracture tendency of α-cellulose and lactose tablets has been investigated. Tablet tensile strength, ( T), packing fraction, ( P f), and brittle fracture index (BFI) were determined at different compression pressures (0.82, 1.22 and 1.63 MPa). In another aspect of the study, α-cellulose and tapioca powders were mixed in various proportions to obtain powders of varying plastoelasticity. Their tableting characteristics T, P f and BFI were also determined at the different compression pressures. The polymer, α-cellulose displayed the characteristics of plastic compression—a low BFI but high T and P f values while lactose displayed the characteristics of elastic compression—a high BFI but low T and P f values. The degree of plastic compression decreased as the proportion of tapioca in the powder mixture increased from 0 to 50% w/w. Higher concentrations of tapioca >50% produced crumbly tablets at all compression pressures, thus indicating that tapioca is highly elastic. Increase in the compression pressure caused an increase in the BFI values of lactose tablets, 0.39–0.76 but a decrease in the BFI values of α-cellulose tablets, 0.38–0.09. This decrease became less pronounced as the plasticity of the powder mixtures decreased. The difference in the response of the tablets to the change in compression pressure relates to the difference in the plastoelasticity of the materials tested.

Effect of acid treatment on the consolidation and plasto-elasticity of tapioca powder

Purpose: The effects of treating the tapioca (the fibrous residue obtained after up to 90% of the proportion of starch has been removed from the peeled and rasped roots of cassava tubers powder with dilute solutions of hydrochloric acid) in order to find an approach for rendering an otherwise poorly compressible material to a directly compressible powder. Method: The parameters measured were the degree of consolidation of the powder after compression (i.e. the packing fraction of resulting tablets), the plasto-elasticity of the powders as reflected by the brittle fracture index (BFI) of the tablets made from the powders and the viscosities of mucilages derived from the powders. The influence of time of exposure and the concentration of acid used in the treatment were studied. Results: The degree of consolidation of the powder increased slightly with increase in duration of exposure to acid (24 — 72 h) but drastically with increase in the acid concentration from 0.1 to 0.4 mol. L—1. On the other hand, the plasto-elasticity of the powders as measured by the BFI values and the viscosities of mucilages derived from the powders decreased slightly with duration of exposure but drastically with increase in acid concentration. A change in acid concentration was therefore the more determinant factor with regards to the consolidation and plasto-elasticity properties of the powders. The decrease in the viscosities of the mucilages following acid treatment of the powders was indicative of a breakdown of polymeric structure in the powder Conclusion: Acid treatment of tapioca powder imparted plasticity in tapioca powder which became compressible. Key words: Plasto-elasticity, brittle fracture index, tapioca powder. Trop J Pharm Res, June 2002; 1(1): 45-49

Compressional Characteristics of Native and Pregelatinized Forms of Sorghum, Plantain, and Corn Starches and the Mechanical Properties of Their Tablets

ABSTRACTA study was made of the compressional characteristics of native and pregelatinized forms of sorghum, plantain, and corn starches and the mechanical properties of their tablets. Compressional characteristics were analyzed using density measurements and the Heckel and Kawakita plots. Pregelatinized starches exhibited more densification than native starches during die filling and at low pressures. The ranking for the mean yield pressure (Py) values for the starches was plantain<corn<sorghum, with the pregelatinized starches having lower values than the native starches. The ranking for the values of another pressure term, Pk—an inverse measure of plasticity, was corn<plantain<sorghum, but with the native starches having the lower values. For the tablets, the ranking for values of tensile strength (T) was corn>plantain>sorghum, while the ranking for the brittle fracture index (BFI) was plantain>corn>sorghum. Tablets made from pregelatinized starches had lower T and BFI values than those made from native starches. The results suggest that pregelatinization of the starches facilitated faster onset of plastic deformation but reduced the amount of plastic deformation which occurred during the compression process.

Indices of Tableting Performance for Acrylic Resin Polymers with Plastic and Brittle Drugs

The indices of tableting performance were used to investigate the compaction properties of two methacrylate ester copolymers (Eudragit® RS PM and RL PM) and three methacrylic acid copolymers (Eudragit® S 100, L 100, and L 100–55). These polymers were designed to be incorporated directly into solid dosage forms for controlled-release purposes. The polymers were combined in the dry state with either sodium sulfathiazole (a brittle drug) or theophylline (a plastic drug) at concentrations ranging from 0 to 100% polymer. All powders were blended for 15 minutes and compacts measuring 1 inch square and weighing 5 g each were made using a die that decompressed triaxially and a Carver® press equipped with a strain gauge. Solid fractions were kept constant at 0.81. Two of the tableting indices, the bonding index (BI) and brittle fracture index (BFI), were studied for all mixtures. The BFI of the sulfonamide (0.49) was nearly three times greater than the BFI for theophylline(0.17) The three methacrylic acid copolymers had high BFI values ranging from 0.99 to 1.60, demonstrating the brittle characteristics of these polymers. The BFI decreased with increasing drug content in all cases. Of the five polymers, the BI was greatest for Eudragit® L 100–55 with both drugs, especially at the 20% drug concentration, followed by Eudragits L 100 and S 100. These three resins were prepared by a spray-drying process. The strongest interactions (positive deviations for the BFI; negative deviations for indentation hardness and BI) of either drug with the polymers were always seen with the spray-dried materials. Low bonding indices were obtained for both of the methacrylate ester copolymers. However, all mixtures of both drug with these milled polymers (RL PM and RS PM) formed successful tablets.

Formulation Effects on the Mechanical Properties of Metronidazole Tablets

The individual and interaction effects of nature of binder (N), concentration of binder (C) and the physical form of the formulation (P) on the tensile strengths (T--a measure of the bond strength of tablets) and the brittle fracture index values (BFI--a measure of the lamination tendency of tablets) of metronidazole tablets have been studied using a 2(3) factorial experimental design in each case. Changing binder concentration from a 'low' to a 'high' level increased T and reduced the BFI of the tablets. Methylcellulose 20 exhibited stronger binding effect and greater ability to reduce the lamination tendency of the tablets than polyvinylpyrrolidone of molecular weight 44,000. Granular formulations produced tablets with lower T values but also with lower BFI values than tablets produced from powdered formulations. The ranking of these individual effects on tensile strength was P greater than C greater than N while the ranking for the BFI was P greater than N greater than C. For the interaction effects, the ranking for tensile strength was P-N much greater than N-C greater than P-C while the ranking for the BFI was N-C much greater than P-C greater than P-N.

Tableting characteristics of metronidazole formulations

A study has been made of the effects of polyvinylpyrrolidone, gelatin and methylcellulose binding agents on the tableting properties of a metronidazole-lactose-starch formulation and on the tensile strengths (T) of tablets produced from both granular and powdered forms of the formulation. The samples' elastic recovery to plastic compression ratios (ER/PC) and their brittle fracture index values (BFI — obtained by comparing tensile strengths of tablets with and without a hole at their centre) decreased with binder concentration while T increased. Tablets made from granules (TABG) had lower T and higher ER/PC than those from powders (TABP) but were also less brittle. Tablets made from granules (TABG) exhibited no fracture problems during the compression cycle but were friable at low concentrations of binders. On the other hand, tablets made from powders (TABP) were non-friable but occasionally laminated or capped. These observations might be anticipated from the measured values of ER/PC and BFI of the materials.