Fracture Index Research Articles

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.

Evaluation of starches obtained from four Dioscorea species as binding agent in chloroquine phosphate tablet formulations

Starches obtained from four Dioscorea species namely Dioscorea dumetorum (Bitter), Dioscorea oppositifolia (Chinese), Dioscorea alata (Water), and Dioscorea rotundata (White) have been evaluated as binding agents in chloroquine phosphate tablet formulations in comparison with official corn starch. The compressional properties of the formulations were analyzed using density measurements and the Heckel and Kawakita equations. The mechanical properties of the tablets were assessed using tensile strength, brittle fracture index (BFI), and friability tests while the drug release properties of the tablets were assessed using disintegration and dissolution times. The results indicate that the four starches vary considerably in their physicochemical properties. The ranking for the tensile strength and the disintegration and dissolution times for the formulations was Chinese > Bitter > Corn > White > Water while the ranking was reversed for BFI and friability. The results suggest that Water, White, and Corn could be useful when faster disintegration time of tablets is desired while Chinese and Bitter could be more useful when bond strength is of concern and in minimizing the problems of lamination and capping in tablet formulation.

New Surrogate Model to Predict Fracture of Laminated CFRP for Structural Optimization

Laminated composite structures are widely used for aerospace components because of their high specific strength and specific stiffness. For laminated composite structures, stacking sequence optimization is indispensable. Although fracture of the laminated composites is usually used as a constraint, it is very important to obtain an accurate approximation of the fracture of the laminated composites for the optimization of surrogate models. Approximating the fracture of laminated composites, however, is quite difficult because the fracture index is very noisy. In the present study, a new surrogate model using the Kriging model for the fracture of laminated composites is proposed and tested for the most severe plate bending problems.

Mikkeli Osteoporosis Index Identifies Fracture Risk Factors and Osteoporosis and Intervention Thresholds Parallel with FRAX

Osteoporosis Index (MOI) was developed from Fracture Index (FI), a validated fracture risk score, to identify also osteoporosis. MOI risk factors are age, weight, previous fracture, family history of hip fracture or spinal osteoporosis, smoking, shortening of the stature, and use of arms to rise from a chair. The association of these risk factors with BMD was examined in development cohorts of 300 Finnish postmenopausal women with a fracture and in a population control of 434 women aged 65–72. Validation cohorts included 200 fracture patients and a population control of 943 women aged 58–69. MOI identified femoral neck osteoporosis in these cohorts as well as the Osteoporosis Self-Assessment Tool (OST). In the pooled fracture cohort, the association of BMI-based FRAX fracture risk with MOI was good. After BMD measurement, MOI identified well FRAX hip fracture risk-based Intervention Thresholds (ITs) (AUC 0.74–0.90).

Studies on Flowability, Compressibility and In-vitro Release ofTerminalia chebula Fruit Powder Tablets.

The dried fruit of Terminalia chebula is widely used for its laxative properties. The objective of the present study was to examine the flowability and compressibility of Terminalia chebula fruit powder, subsequently developing its tablet formulations by utilizing wet granulation and direct compression technology. Initial studies on flowability and compressibility revealed that the fruit powder flows poorly, is poorly compressible and mucilaginous in nature. The consolidation behaviors of the fruit powder and of its tablet formulations were studied using the Kawakita, Heckel and Leuenberger equations. Kawakita analysis revealed reduced cohesiveness hence improved flowability was achieved in formulations prepared by direct compression and the wet granulation technique. The Heckel plot showed that the Terminalia chebula fruit powder when formulated using direct compression showed initial fragmentation followed by plastic deformation and that the granules exhibited plastic deformation without initial fragmentation. The compression susceptibility parameter obtained from the Leuenberger equation for compacts formed by using the direct compression and wet granulation techniques indicated that the maximum crushing strength is reached faster and at lower compression pressures. The Tannin content (with reference to standard tannin) in fruit powder and tablet formulations was determined by UV spectrophotometry at 273 nm. The in-vitro dissolution study in simulated SGF (without enzymes) showed more than a 90% release of tannin from the tablets with in 1 h. The brittle fracture index value revealed that tablets prepared from granules showed less fracture tendency in comparison to those formed by direct compression formulation. From this study, it was concluded that the desired flowability, compressibility and compactibility of Terminalia chebula fruit powder can be obtained by using the direct compression and wet granulation techniques.

Evaluation of the Quantitative Effects of Variables on a Paracetamol Tablet formulation Prepared with Gum as Binding Agent

The individual and interaction effects of gum - binder type (B), binder concentration (C), as well as the relative density (D) of a paracetamol tablet prepared with Delonix regia seed gum (DRSG), acacia gum BP (ACG) and tragacanth gum BP (TRG) on the mechanical {tensile strength (TS) and brittle fracture index (BF} and disintegration {disintegration time (DT) and crushing strength-friability/disintegration time ratio (CSFR/DT)} properties of the tablets were studied using a 2 3 factorial experimental design. For the TRG/ACG and DRSG/ACG, the individual effects of the variables presented a rank order of D>C>B on the two mechanical properties studied, while a rank order of B>C>D was obtained for the studied disintegration properties. However, considering the TRG/DRSG combination, effect of C was more on the DT (C>D>B), whereas D had more effect on the CSFR/DT (D>C>B). Generally, the interaction between B and C was more on TS and DT than on BFI and CSFR/DT, while a similar result was observed for B and D on BFI and CSFR/DT than on TS and DT. This implies that the B is a very important variable to be considered when combining binders in a formulation.

A quantitative study of the influence of coprocessing of binders on the mechanical properties of paracetamol tablets

A 2³ factorial experimental design has been used to quantitatively study individual and interaction effects of the nature of binder (N), concentration of binder (C) and the applied pressure (P) on two mechanical properties, namely, tensile strength (TS) and brittle fracture index (BFI), of paracetamol tablets. The factorial design was also used to study the quantitative effects of coprocessing of binders on the mechanical properties. The results obtained from this study suggest that the nature (i.e. plastic/elastic) and ratio of binders coprocessed together alter the influence of C and P on TS and BFI.

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.

Can Fiber Posts Increase Root Stresses and Reduce Fracture?

The clinical success of fiber posts has been attributed to their lower elastic modulus. The tested hypothesis was that fiber posts could lead to lower risk of post debonding and lower risk of root fracture, despite an increase in root stresses. Stress analyses were carried out with a 3D finite element model of a premolar restored with a metallic or a fiber post. Bonded and non-bonded post/cement interface conditions were simulated. We calculated risk-of-fracture indices by determining the highest principal stress values divided by the tensile strength. Shear stresses along the post/cement interface were analyzed for the bonded models. Compared with the premolar restored with a metallic post, the fiber post generated lower stresses along the interface and higher stresses in the root. However, with the fiber post, fracture was less likely to occur in the root, since its core and post fracture indices were higher.

3D fracture modeling in Parsi oil field using artificial intelligence tools

Abstract Naturally fractured reservoirs are generally complex and highly heterogeneous. There are usually scarce data sources in these reservoirs that may be found over a wide range of scales. Therefore, fracture characterization is a complicated task and an integrated method is required to effectively overcome this multi-scaled problem and to combine data obtained from as many tools as possible. One sophisticated tool for this purpose is artificial intelligence. Recently, Fuzzy Logic and Neural Network have been used to obtain a 2D fracture intensity map in Hassi Messaoud field. The aim of this paper is to show the applicability of Artificial Neural Network and Fuzzy Logic in characterizing Parsi naturally fractured reservoir. First, using Fuzzy Inference System (FIS), Fracture Index (Fracture Intensity Index or FI) is calculated along the wellbore. For decreasing the uncertainty, using FIS, static and dynamic data (log, well test and core data) are coupled which results in a more reliable Fracture Index. Moreover, use of log data in FIS makes it possible to calculate the fractured index in those blocks where wells are perforated. Hence, a 3D characterization becomes possible. Then, for calculating the spatial distribution of the Fracture Index, two types of Neural Networks, Multi-Layer Perceptron (MLP) and Radial Basis Function (RBF), are used. The inputs of these networks are some geological and geomechanical drivers (e.g. shale volume, porosity, permeability, bed thickness, proximity to faults, slopes and curvatures of the structure), and the output is the Fracture Index. Because of the overfitting problem in MLP network, fuzzy ranking method is used for selecting only parts of the mentioned drivers as inputs of MLP network, and also a partially connected MLP network are used. RBF network produces more reasonable Fracture Index. Next, a 3D fracture intensity map in Parsi oil field is developed. According to this map, the high production rate of some wells can be explained in this field. Also, this 3D fracture intensity map can reduce the uncertainty in reservoir simulation. Therefore, a better field development scenario can be designed. The results are promising and can be easily extended in other naturally fractured reservoir.

Evaluation of Hibiscus esculentus Linn. on the Mechanical and Disintegration Properties of Paracetamol Tablets

The effects of mucilage obtained from the ripe fruits of Hibiscus esculentus Linn. (Malvaceae) on the mechanical and disintegration properties of paracetamol tablets were investigated against gum acacia as a standard binding agent. The effects of the nature and concentration of the mucilage binder and the relative density of the tablet on the tensile strength, brittle fracture index and disintegration time of the tablets were investigated. Relative density, concentration and nature of binder had the greatest effects on tensile strength, brittle fracture index and disintegration time,respectively. Increasing, the concentration of mucilage from 2.5 % to 10.0 % w/w, and increasing relative density of the tablet from 0.70 to 0.80 led to an increase in tensile strength and disintegration time, but a decrease in brittle fracture index. Tablets formulated with H. esculentus mucilage had lower tensile strength and disintegration time values than those containing gum acacia, and exhibited less lamination and capping. The nature and concentration of binder had the highest interaction among the factors studied. In conclusion, Hibiscus esculentus mucilage could be useful as an alternative binding agent to gum acacia, especially wherefaster disintegration is required and lamination and capping are of concern.

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.

Riesgo de fracturas no vertebrales en mujeres posmenopáusicas en tratamiento antirresortivo

ObjectiveTo determine the 5-year non-vertebral fracture risk in postmenopausal women on antiresorptive therapy. Subjects and methodsWe performed a cross-sectional multicenter study in 2,111 postmenopausal women receiving antiresorptive therapy in gynecological settings. The risk of fracture was evaluated by means of the FRACTURE Index. The influence of clinical parameters on the main variable was evaluated through linear and/or logistic regression, using the SAS v. 9.1.3 program. ResultsThe mean age ± standard deviation was 61.0 ± 7.9 years. Densitometry was available in 60.5% of the women and showed a prevalence of osteopenia of 49.4% whereas that of osteoporosis was 42.4%. Biphosphonates were used in 59.3% of the women. When densitometry was available, 73.4% scored less than 6 points on the FRACTURE Index, and when densitometry was not available, 81.7% scored less than 4 points. The mean risk of non-vertebral fractures was 14.8 ± 5.3% and that of vertebral fractures was 4.0 ± 3.0%. ConclusionsIn this large group of postmenopausal women receiving antiresorptive treatment, the 5-year non-vertebral fracture risk, as assessed by the FRACTURE index, was three times higher than that of vertebral fracture.

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.

Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing’s syndrome

Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women. Currently, it is unclear if patients with subclinical Cushing's syndrome (SCS) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given. This pilot randomized study was aimed at evaluating the effects of 12-month im administration of clodronate (100 mg every week) on vertebral and femoral bone mineral density (BMD), bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas. Forty-six women (age, 43.1+/-7.7 yr) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were randomized to receive clodronate plus supplement of Calcium (500 mg daily) and Vitamin D3 (800 mg daily) (group 1, no.=23) or supplements only (group 2, no.=23). Both groups were similar in terms of age, body mass index, cortisol levels, BMD values, and bone turnover markers. All of the women were re-evaluated after 12 months. After 12 months of treatment, in group 1, a significant increase in lumbar BMD occurred (p=0.04), while bone turnover markers decreased by about one third (p<0.05). In group 2, bone turnover markers did not change and BMD values slightly decreased (p=ns). The differences in bone turnover markers and in lumbar BMD between the two groups were significant (p<0.05, all). No new vertebral fracture occurred in group 1, while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures. An improvement in subjective back pain, assessed by visual analogue scale pain score was observed in group 1 (from 4.3+/-2.7 to 2.9+/-2.0; p<0.05) but not in group 2 (from 4.4+/-3.1 to 4.2+/-3.4; p=ns). No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study. Intramuscular administration of clodronate effectively increased lumbar BMD values, preserved bone mass at the femoral neck, stabilized vertebral fracture index, and decreased subjective back pain in pre-menopausal women with SCS. Since the untreated group continued to lose bone, antiresorptive treatment should be considered in patients with SCS, according to the prevision of surgical treatment, prevalent fractures, BMD values, age, concomitant morbidities, and desire for pregnancy.

A Comparison of Frailty Indexes for the Prediction of Falls, Disability, Fractures, and Mortality in Older Men

To compare the validity of a parsimonious frailty index (components: weight loss, inability to rise from a chair, and poor energy (Study of Osteoporotic Fractures (SOF) index)) with that of the more complex Cardiovascular Health Study (CHS) index (components: unintentional weight loss, low grip strength, poor energy, slowness, and low physical activity) for prediction of adverse outcomes in older men. Prospective cohort study. Six U.S. centers. Three thousand one hundred thirty-two men aged 67 and older. Frailty status categorized as robust, intermediate stage, or frail using the SOF index and criteria similar to those used in CHS index. Falls were reported three times for 1 year. Disability (>or=1 new impairments in performing instrumental activities of daily living) ascertained at 1 year. Fractures and deaths ascertained during 3 years of follow-up. Analysis of area under the receiver operating characteristic curve (AUC) statistics compared for models containing the SOF index versus those containing the CHS index. Greater evidence of frailty as defined by either index was associated with greater risk of adverse outcomes. Frail men had a higher age-adjusted risk of recurrent falls (odds ratio (OR)=3.0-3.6), disability (OR=5.3-7.5), nonspine fracture (hazard ratio (HR)=2.2-2.3), and death (HR=2.5-3.5) (P<.001 for all models). AUC comparisons revealed no differences between models with the SOF index and models with the CHS index in discriminating falls (AUC=0.63, P=.97), disability (AUC=0.68, P=.86), nonspine fracture (AUC=0.63, P=.90), or death (AUC=0.71 for model with SOF index and 0.72 for model with CHS index, P=.19). The simple SOF index predicts risk of falls, disability, fracture, and mortality in men as well as the more-complex CHS index.

71 Conception of a Composite Osteoporosis Fracture Index Including Bone Texture Analysis and Bone Mineral Density

71 Conception of a Composite Osteoporosis Fracture Index Including Bone Texture Analysis and Bone Mineral Density

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 (

Épidémiologie de l'ostéoporose

Osteoporosis leads to fragility fractures. Fracture incidence increases after the menopause among women and with age in both genders. More than 40 % of women will sustain at least one fragility fracture after the age of 50. Many risk factors have been described, including age, familial history of fracture, low bone mineral density, personal history of fracture, smoking and low body mass index. Fracture incidence is increasing worldwide, owing to population aging. Hip and vertebral fractures are associated with increased mortality and morbidity. Costs related to fragility fractures represent a significant burden for health care systems.