Increase In Compression Force Research Articles

Arthroscopic Fixation of Matrix-Associated Autologous Chondrocyte Implantation: Importance of Fixation Pin Angle on Joint Compression Forces

The aim of the study was to investigate the effect of pin fixation perpendicular and 30° tilted to the matrix surface on the joint compression forces. In a porcine knee model, joint compression forces were recorded with a digital pressure sensor above the medial meniscus and with axial compression of 100 N by use of a material testing machine. The forces were recorded for an intact femoral condyle, as well as a standardized cartilage defect of 25 × 20 mm, after matrix-associated autologous chondrocyte implantation (m-ACI) (BioSeed C; Biotissue Technologies, Freiburg, Germany), fixed by use of a conventional suture technique and pin fixation with a biodegradable pin perpendicular and 30° tilted to the matrix surface. In knees with cartilage defects, the peak compression forces (mean, 824 kPa) were significantly increased compared with the intact knee joint (564 kPa). After m-ACI implantation with a chondral suture (581.3 kPa) and perpendicular pin fixation, the joint compression forces of the cartilage defect were significantly decreased (630.7 kPa). There were no significant differences compared with the intact knee. After 30° tilted pin insertion, mean joint compression forces were significantly increased (1,740 kPa). This study shows that after chondral suture and perpendicular pin fixation, there are no increased compression forces in the knee joint in comparison to an intact knee. Thirty degree tilted pin insertion contributes to increased joint compression forces. A tilted insertion during pin fixation in m-ACI should be avoided because it may lead to increased joint compression forces, especially after cartilage defect lesions on the tibial side.

The effect of moisture on the heckel and energy analysis of hydroxypropylmethylcellulose 2208 (HPMC K4M).

The influence of moisture content on the Heckel analysis, energy analysis and strain-rate sensitivity of hydroxyproplymethylcellulose 2208 (HPMC K4M) has been evaluated. An increase in moisture content from 0 to 14.9% w/w decreased the mean yield pressure, probably due to a plasticizing effect of moisture which reduced the resistance of particles to deformation. For each moisture content (0, 2.2, 3.8, 5.9, 9.6 and 14.9% w/w), the initial relative density and the extrapolated density from the linear portion of the Heckel plot, tended to decrease with increasing compression speed. Minor changes were observed in the initial relative density due to changes in the moisture content. The strain-rate sensitivity increased from 21.6 to 50.7% as the moisture content increased from 0 to 14.9% w/w, indicating that the plasticity of HPMC increased with increase in moisture content, whereas increase in moisture content from 0 to 14.9% w/w decreased the plastic energy. Increase in compression force or speed of compaction increased both the plastic and elastic energies. An increase in moisture content from 0 to 5.9% w/w slightly reduced the elastic energy but above 5.9% moisture content the elastic energy was unaffected by the moisture content.

Improvement of Drop-Hammer Compression Test for Rubber Material

The drop-hammer compression testing method where the stroke is calculated by solving the equation of motions of the drop-hammer and anvil was improved in order to determine the strain-rate dependence of the elastic modulus of rubber material. An additional tool for interrupting the compression was embedded in the apparatus. The tool was a thick washer which informed the time when the prescribed compressive strain was achieved by the sharp increase of compression force. The oscillatory stress-time curve obtained by the load cell was appropriately smoothed employing the method of moving average. The effect of the friction at the interface between the rubber specimen and the tools was properly eliminated by the extrapolating method using the specimens with several variations in heights. The stress-strain relationship was obtained under the dynamic condition. The numerical simulation of impact compression disclosed that the effect of inertia on the deformation pattern was practically small under the experimental condition adopted. Conducting the low-speed compression tests, the dependence in elastic modulus of rubber material on the strain-rate was appropriately determined.

Compression behaviour of κ-carrageenan pellets

The compression behavior of high- and low drug strength pellets containing κ-carrageenan as pelletisation aid was investigated. Model drugs and fillers with different compression mechanisms were used and the effects of compression force and turret speed were examined. Regardless of the compression behavior of their starting components, all pellet formulations exhibited minimal to absent fragmentation and underwent compression by deformation, confirmed by increased equivalent diameter and aspect ratio and decreased roundness factor of the pellets retrieved after de-aggregation of tablets prepared from lubricated pellets. The retrieved pellets showed also higher fracture resistance in three of the tested formulations and no statistically significant difference in the remaining one thus excluding significant crack formation. A densification mechanism was suggested by decreased total porosity and reduced median pore radius of the compressed pellets. No effect of the process parameters on the degree of pellet deformation was reported. The tensile strength of the tablets prepared from unlubricated pellets increased slightly with increased compression force. Compression of pellets with high density silicified microcrystalline cellulose (SMCC HD 90) as embedding powder protected them from severe deformation and resulted in tablets with sufficient tensile strength, minimal friability, negligible elastic recovery and short disintegration time. The percentage of the pellets and the compression force affected the tensile strength of the prepared tablets whereas no influence of the turret speed and the pre-compression force was observed.

Effect of Compression Pressure on Dissolution and Solid State Characterization of Cefuroxime Axetil

The current work aims to investigate the sudden drop of dissolution with respect to higher compression pressure and hardness of tablet with a good and comparative less significant disintegration time and to understand an affect of pressure on drug with respect to compression behavior on dissolution and other properties. Where Cefuroxime Axetil was compressed at different pressure in form of pellets and tablets using hydraulic press and compression machine respectively, and characterized to understand any physical and chemical change using X-ray powder diffraction, differential scanning calorimetry, and Dissolution and Scanning Electron microscopy. Scanning electron microscopy studies of pellets revealed that the change in surface morphology from opaque to translucent clear with increase in breaking force, these different pressure compressed pellets were subjected to uniform reduction of particle size. The similarity factor f2 values of drug release profile were comparably same. The breaking force and pellet hardness had indicated a very firm intrinsic binding force exist with Cefuroxime Axetil, study had investigated the decrease in-vitro dissolution is marked by the compact binding property of individual particles of Cefuroxime Axetil between the excipient due to the increase in compression force.

Characterization of bulking agents and its effects on physical properties of compost

Objective was to enquire the attributes of regionally obtainable BA (bagass, paper, peanut shell, sawdust) to inscribe the efficacy of BA at (10–40%) for moisture reduction. Sawdust was prominent in moisture reduction capability in 5–7 days. The prime physical changes in BA under various compression forces were as; by increasing compression force, BD rise and FAS decline, whereas PD had not exhibit any discrepancy. Proficient compost production entails meticulous understanding the process dynamics in terms of correlation between moisture reduction; FAS, BD and PD. FAS and moisture were negatively where as BD and moisture positively correlated.

Effect of some physical parameters and crospovidone on directly compressed frusemide tablets

The aim of this study was to evaluate the effect of increasing crospovidone (superdisintegrant) load on the characteristics of fast-disintegrating tablets for the potential use of the drug for its therapeutic effect. Five tablet formulations, F0, F1, F3, F7, and F10 containing 0%, 1%, 3%, 7%, and 10% (w/w) of crospovidone, respectively, frusemide and microcrystalline cellulose (PH102), were prepared by direct compression, at a different compression forces.Tablet weight variation, content uniformity, crushing strength, disintegration time, wetting time, and in vitro release were measured for each formulation at each compression force. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration and wetting times was observed for the formulations F0, F1, F3 with the increase in compression force.The tablet formulation F7 indicated, there was no effect of compression force on disintegration and wetting time. The in vitro release of the drug was increased with increase in concentration of crospovidone irrespective the compression force. However, storage under high humidity conditions caused the softening of the tablets containing the high amount of crospovidone, leading to softening of tablets. Fast disintegration of the tablets within 1-2 min is prerequisite for improving the dissolution of frusemide, attributed to increase in speed at which maximum surface area of sparingly soluble drug is exposed to the dissolution medium. However, tablet containing high amount of crospovidone must beprotected from the atmospheric moisture because storage of these tablets at high humidity led to softening and losing the tablet characteristics.

Design and in Vitro Evaluation of Zidovudine Oral Controlled Release Tablets Prepared Using Hydroxypropyl Methylcellulose

Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine.

Design and study of lamivudine oral controlled release tablets.

The objective of this study was to design oral controlled release matrix tablets of lamivudine using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, and compression force on the in vitro release of drug. In vitro release studies were performed using US Pharmacopeia type 1 apparatus (basket method) in 900 mL of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using the zero-order model equation, Higuchi's square-root equation, and the Ritger-Peppas empirical equation. Compatibility of the drug with various excipients was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 60% HPMC 4000 cps were found to show good initial release (26% in first hour) and extended the release up to 16 hours. Matrix tablets containing 80% HPMC 4000 cps and 60% HPMC 15,000 cps showed a first-hour release of 22% but extended the release up to 20 hours. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of lamivudine, with good initial release (20%-25% in first hour) and extension of release up to 16 to 20 hours, can overcome the disadvantages of conventional tablets of lamivudine.

A Study of the Properties of Compacts from Silicified Microcrystalline Celluloses

ABSTRACTThe paper deals with a study of tensile strength and disintegration time of compacts made from silicified microcrystalline celluloses, Prosolv SMCC 90, and Prosolv HD 90, in dependence on compression force, addition of two types of lubricants, and two active ingredients. The lubricants were magnesium stearate and sodium stearyl fumarate in a concentration of 0.5%, the active ingredients being ascorbic acid and acetylsalicylic acid in a concentration of 50%.Prosolv SMCC 90 proved to be better compatible than Prosolv HD 90; the compacts were of higher strength, which was markedly increased with increasing compression force. Prosolv HD 90 was more sensitive to additions of lubricants, and a greater decrease in strength was recorded due to the influence of sodium stearyl fumarate. The effect of lubricants on the strength of compacts in the presence of active ingredients was not identical. The disintegration time of compacts from Prosolv HD 90 without as well as with lubricants was shorter than from Prosolv SMCC 90 and was increasing with increasing compression force. Disintegration time was increased with added lubricants, and it was markedly shortened by addition of active ingredients. Compacts containing ascorbic acid possessed a shorter disintegration time than those containing acetylsalicylic acid, and it was not markedly influenced by the presence of lubricants.

Fast-disintegrating sublingual tablets: effect of epinephrine load on tablet characteristics.

The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9:1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content uniformity, hardness, disintegration time, wetting time, and friability were measured for each formulation at each compression force. All 4 tablet formulations at each compression force were within the United States Pharmacopeia (USP) limits for weight variation and content uniformity. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration and wetting times of A, and an exponential increase in disintegration and wetting times of B, C, and D. At a mean +/- SD hardness of > or = 2.3 +/- 0.2 kg, all tablet formulations passed the USP friability test. At a mean +/- SD hardness of < or = 3.1 +/- 0.2 kg, all tablet formulations resulted in disintegration and wetting times of <10 seconds and <30 seconds, respectively. Tablets with drug loads from 0% to 24% epinephrine can be formulated with hardness, disintegration times, and wetting times suitable for sublingual administration.

Starch and pectin solubilization and texture modification during pre-cooking and cooking of cassava root ( Manihot esculenta Crantz)

Physico-chemical alterations of cell-wall constituents and of substances stored in the cell characterize the behavior of fresh vegetables during cooking. Pre-cooking for 1 h at three different temperatures was used to identify alterations in hydration, pectin and starch solubilization and the relation to texture determination by a compression and a shear test. Samples of cassava ( Catarina amarela) harvested 8 months after planting date were used. Soluble galacturonic acid in the treatment water varied from 0.07 to 0.2.1 mg/100 ml while soluble solids varied from 271.3 to 599.6 mg/100 ml. Soluble starch varied from 114.3 to 437.7 mg/100 ml and total solids varied from 292.4 to 611.4 mg/100 ml during pre-cooking from 55 to 75 °C. There was weight reduction of 4 and 2 g/100 g of material and reduction of compression force in the treatments at 55 and 65 °C in relation to the raw sample and weight gain of 6.7 g/100 g and increase in compression force at 75 °C. Shear force decreased from the raw sample to the 65 °C treated sample while pectin solubility increased up to 75 °C. Samples cooked in boiling water had weight gain of 6.8 g/100 g of material, 493.3 mg/100 ml of soluble solids and 588 mg/ 100 ml of total solids of which 507.6 mg was starch.

Atomic Force Microscopy Studies of Mesoscopic Membranous Bubbles on Monolayers Derived from SiCl3-Terminated Carbosilane Dendrons on Mica

Monolayers of dendrimers were prepared on mica by spin-coating of the second generation carbosilane dendrons with 9 SiCl(3) periphery groups. AFM images of the films showed the presence of soft yet robust, dome-shaped features with a base diameter of 100-2000 nm. The apparent height of the features, ranging from 10 to 200 nm, rapidly reduced under increasing compression force, eventually to the same value ( approximately 2.5 nm) corresponding to a bilayer of the flattened dendrons. The change in shape of the features in response to the compression force from the AFM tip was fully reversible, indicating that the features were robust. The contrast of the features in the tapping mode AFM (TMAFM) phase images flipped at a setpoint ratio of approximately 0.55. In contrast to the reported amplitude vs displacement (A/z) curves for compliant materials, A/z curves of the features showed that the reduction of amplitude was larger than the tip displacement as if the cantilever tip were repelled by the soft features. This result cautions the use of amplitude/phase vs displacement (APD) curves for interpreting TMAFM images and for optimizing conditions for TMAFM imaging of very soft and "sticky" surfaces. On the basis of the AFM studies, we believe that the dome-shaped features are membranous air bubbles. The membranes of the bubbles were probably composed of a bilayer of the dendron molecules bound through the peripheral silanol groups. The bilayer could be formed by self-assembly of the molecules on top of the air bubbles entrapped at the monolayer/solution interface during spin-coating.

Evaluation of Different Fast Melting Disintegrants by Means of a Central Composite Design

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X1) and the compression force (X2). These factors were studied for tablets containing either Zeparox® or Pearlitol 200® as soluble diluents and six different disintegrants: L-HPC® LH11 and LH31, Lycatab PGS®, Vivasol®, Kollidon CL®, and Explotab®. Their micromeritics properties were previously determined. The response variables were disintegration time (Y1), tensile strength (Y2), and porosity (Y3). Whatever the diluent, the longest disintegration time is obtained with Vivasol® as the disintegrant, while Kollidon CL® leads to the shortest disintegration times. Exception for Lycatab PGS® and L-HPC LH11®, formulations with Pearlitol 200® disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox® as the diluent when compared to Pearlitol 200® and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS® concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200® is used with Vivasol®, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox®, the interaction between the two controlled variables is more complex: there is no effect of compression force on the disintegration time for a small amount of disintegrant, but a significant increase for higher concentrations. With Kollidon CL®, the main factor influencing the disintegration time is the compression force, rather than the disintegrant concentration. Increasing both the compression force and the disintegrant concentration leads to an increase of the disintegration time.For lower Kollidon CL® percentages, the compression pressure increases dramatically the tablet disintegration. With the Explotab®, whatever the increase of compression force, the disintegrant concentration leads to an increase of the disintegration time. According to Student's t-test, only the compression force significantly and strongly influences the disintegration time when Pearlitol 200® is used. A slight interaction and some trends nevertheless appear: above 150 MPa, increasing the disintegrant concentration leads to a shortened disintegration time, below this limit the opposite effect is observed.

Developing Functional Foods Using Red Palm Olein: Objective Color and Instrumental Texture

Edible red palm olein (RPOL) has been newly developed by the Malaysian Palm Oil Board for use in food products to enhance their nutritional value. The results of the effect of RPOL and red palm shortening (RPS) on the objective color and instrumental texture of these functional foods are presented. The results indicate that using up to 100% RPS in the test bread samples did not have any adverse effect on the textural quality of the samples, with the results being comparable with the respective control breads. However, increasing the level of RPOL caused a simultaneous increase in compression force with the values being highest at the 100% replacement level. Replacement with RPOL in bread formulations at the 100% level increased the compression force to 15.2 N for whole-wheat bread, 7.5 N for white bread, and 11.7 N for 20% bran (0.2 kg bran/kg flour) bread over that of control whole-wheat bread (8.3 N), control white bread (3.3 N), and control 20% bran bread (4.2 N). This indicates that RPOL does not perform as well in pan bread as compared with RPS. Using 0.5% diacetyl tartaric acid esters of monoglycerides (DATEM) in bread formulations produced a decrease in compression force values at all combination levels of RPS and RPOL, thus producing a softer product. As RPOL and RPL are extremely rich in carotene pigments (727 ppm), the major changes in crumb color were observed in the yellowness values (b*). The results indicate that increasing the level of RPS or RPOL in test bread samples caused a similar increase in crumb color yellowness values (b*), with a higher increase observed due to increased levels of RPOL.

Exploring Ni–Si thin-film reactions by means of simultaneous synchrotron X-Ray diffraction and substrate curvature measurements

We propose a new approach to follow stress development during solid state reaction between a Ni thin film and Si (0 0 1). Substrate curvature measurements were performed simultaneously with X-ray diffraction at LURE synchrotron radiation facility. The measured curvature yields the average force whereas X-ray diffraction yields the different phases that form as well as the strain variation undergone by these phases. During annealing with a constant heating rate of 2 °C/min, Ni grain growth is first observed, followed by the formation of Ni 2Si, Ni 3Si 2 and then NiSi. The Ni 2Si formation is correlated with a rapid increase in compressive force. At the end of Ni consumption, the force evolves in tension until NiSi formation, which is accompanied by an additional increase in compressive force and then a final force relaxation at higher temperature. It is interesting to note that the NiSi phase appears at the expense of Ni 3Si 2, and surprisingly, at the benefit of Ni 2Si until the Ni 3Si 2 is completely consumed. Strain buildup during Ni 2Si and Ni 3Si 2 formation exhibit clear differences. Both Ni 3Si 2 and Ni 2Si phases exhibit a bell shape behavior of the strain evolution versus temperature at variance with predictions from the Zhang and d’Heurle model [Thin Solid Films. 213, 1992, 34].

Accuracy of haptic assessment of patellar symmetry in total knee arthroplasty

Resection resulting in asymmetrically thick patellar arthroplasty in knee arthroplasty may lead to increased compression forces, wear, fracture, or loss of quadriceps power. Assessing the cut patella between the thumb and forefinger (haptic assessment) represents a convenient way to recognize asymmetry. In 2 test series, 8 orthopedic surgeons evaluated 24 precut solid foam patellae of varying asymmetric thickness by feeling the patella between thumb and forefinger, without visualization. Of 384 responses, in 73.2% asymmetry was underestimated, 10.4% assessments were exact, and in 16.4% asymmetry was overestimated. Specifically, 35.9% were correct within 1 mm, 60.7% within 2 mm, 81% within 3 mm, and 91.4% within 4 mm. The thickest half of the patella was correctly identified in 90.6% of responses. Haptic assessment of patellar symmetry is a useful technique in knee arthroplasty.

Transacylation of citrus pectin as catalyzed by pectinesterase from tendril shoots of chayote [ Sechium edule (Jacq.) Swartz

Transacylation reaction of citrus pectin by PE from tendril shoots of chayote (TSC) was observed by gel permeation chromatography (GPC), gel compression force, change in viscosity, and change in turbidity. Molecular mass of pectin remarkably increased from 70 to 443 and 670 kDa when pectin–TSC PE (4 units/ml) mixture in 0.2 M NaCl/0.01 M phosphate buffer (pH 6.5) was incubated at room temperature for 30 min and 2 h, respectively. Apparent increase in compression force (g) of 1% calcium-free pectin gel containing 0.8–16 units/ml of PE after incubation at room temperature for 30 min was observed, revealing the polymerization of pectin as affected by PE transacylation. Increase in viscosity of 0.5% pectin–PE solution (3–30 units/ml) during incubation for up to 60 min, and turbidity change (400 nm) of pectin–PE solution versus PE activity, reaction time, temperature, or NaCl level also evidenced the polymerization of pectin. PE transacylation appeared to be contributory to the pectin gel preparation in food industry.

Knee pain in the ACL-deficient osteoarthritic knee and its relationship to quality of life.

Pain during activities of daily living is a common presenting complaint of individuals with knee osteoarthritis and anterior cruciate ligament injury. Knee pain is also associated with a decrease in quality of life for people with osteoarthritis. The purpose of the present study was to examine the dose-response relationship between knee joint forces and painful symptoms, and whether the acute symptoms, were associated with individuals' quality of life. This was a cross-sectional cohort correlation study. Seventeen individuals with anterior cruciate ligament (ACL)-deficient knees diagnosed with ipsilateral knee osteoarthritis completed the ACL quality of life questionnaire (ACL-QOL). The subjects also rated pain associated with each of five incremental isometric knee extension tests, proportional to their body weight. Analysis of variance was used to assess the association between pain and normalized torque. Linear regression was used to assess the correlation between the ACL-QOL score and the total pain experienced during the graded test. A strong relationship was found between the level of perceived knee pain and the amount of isometric torque produced (Pearson's r = 0.98; p < 0.001). There was a statistically significant relationship between pain during the graded isometric test and the ACL-QOL (Pearson's r = -0.56; p = 0.016). Since knee joint compression is a function of active isometric knee extension torque, increased painful symptoms were associated with increased compression forces at the knee joint for these subjects. The relationship between pain provocation and disease-specific quality of life provides evidence for the proposed joint provocation test for this subject population. Weakness caused by osteoathritis (OA) may, in part, be a negative conditioning response that would need to be overcome in rehabilitation.

Effect of compression force, humidity and disintegrant concentration on the disintegration and dissolution of directly compressed furosemide tablets using croscarmellose sodium as disintegrant

Purpose: The effect of compression force, relative humidity and disintegrant concentration on furosemide dissolution in directly compressed furosemide/Avicel-tablets was studied. Methods: Mixtures of furosemide (12.5% w/w), Ac-Di-Sol (0, 0.625% to 10% w/w) and Avicel PH200 (qs to 100% w/w) were prepared in a Turbula mixer at 69 rpm for 10 min. Tablets were stored for 6 months under conditions similar to the four climatic zones recognized by ICH. Tablet hardness, disintegration time and dissolution were measured. Results: At the same compression force, disintegration time decreased as the disintegrant concentration increased above 0.625% w/w but an increase in compression force resulted in increased tablet crushing strength and apparent density, both of which prolonged the disintegration time. This effect was less significant when the disintegrant concentration was above 1.25%. However, storage under high relative humidity conditions (mediterranean or subtropical, hot and humid climate) caused softening of tablets leading to the spontaneous disintegration of tablets containing high concentrations of Ac-Di-Sol  . Conclusion: Fast disintegration of tablets within 1-2 min is a prerequisite for improving the dissolution of furosemide. This was attributed to an increase in the speed at which the maximum surface area of the sparingly water-soluble drug is exposed to the dissolution medium. Ac-Di-Sol  was an efficient disintegrant for furosomide tablets at low concentrations of 1.25% - 10% because it rapidly released the hydrophobic drug particles from tablets. However, tablets containing 10 % disintegrant must be protected from atmospheric moisture because storage at 60-70 % relative humidity led to softening of tablets.