Effect of polysulfonate resins and direct compression fillers on multiple-unit sustained-release dextromethorphan resinate tablets

The purpose of this work was to investigate the effect of different polysulfonate resins and direct compression fillers on physical properties of multiple-unit sustained-release dextromethorphan (DMP) tablets. DMP resinates were formed by a complexation of DMP and strong cation exchange resins, Dowex 50 W and Amberlite IRP69. The tablets consisted of the DMP resinates and direct compression fillers, such as microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), and spray-dried rice starch (SDRS). Physical properties of tablets, such as hardness, disintegration time, and in vitro release, were investigated. A good performance of the tablets was obtained when MCC or SDRS was used. The use of rod-like and plate-like particles of Amberlite IRP69 caused a statistical decrease in tablet hardness, whereas good tablet hardness was obtained when spherical particle of Dowex 50 W was used. The plastic deformation of the fillers, such as MCC and SDRS, caused a little change in the release of DMP. A higher release rate constant was found in the tablets containing DCP and Dowex 50 W, indicating the fracture of the resinates under compression, which was attributable to the fragmentation of DCP. However, the release of DMP from the tablets using Amberlite IRP69 was not significantly changed because of the higher degree of cross-linking of the resinates, which exhibited more resistance to deformation under compression. In conclusion, the properties of polysulfonate resin, such as particle shape and degree of cross-linking, and the deformation under compaction of fillers affect the physical properties and the drug release of the resinate tablets. Published: September 30, 2005.     

Spherical composite particles of rice starch and microcrystalline cellulose: A new coprocessed excipient for direct compression

Composite particles of rice starch (RS) and microcrystalline cellulose were fabricated by spray-drying technique to be used as a directly compressible excipient. Two size fractions of microcry stalline cellulose, sieved (MCS) and jet milled (MCJ), having volumetric mean diameter (D₅₀) of 13.61 and 40.51 μm, respectively, were used to form composite particles with RS in various mixing ratios. The composite particles produced were evaluated for their powder and compression properties. Although an increase in the microcrystalline cellulose proportion imparted greater compressibility of the composite particles, the shape of the particles was typically less spherical with rougher surface resulting in a decrease in the degree of flowability. Compressibility of composite particles made from different size fractions of microcrystalline cellulose was not different; however, using MCJ, which had a particle size range close to the size of RS (D₅₀=13.57 μm), provided more spherical particles than using MCS. Spherical composite particles between RS and MCJ in the ratio of 7∶3 (RS-MCJ-73) were then evaluated for powder properties and compressibility in comparison with some marketed directly compressible diluents. Compressibility of RS-MCJ-73 was greater than commercial spray-dried RS (Eratab), coprocessed lactose and microcrystalline cellulose (Cellactose), and agglomerated lactose (Tablettose), but, as expected, lower than microcrystalline cellulose (Vivapur 101). Flowability index of RS-MCJ-73 appeared to be slightly lower than Eratab but higher than Vivapur 101, Cellactose, and Tablettose. Tablets of RS-MCJ-73 exhibited low friability and good self-disintegrating property. It was concluded that these developed composite particles could be introduced as a new coprocessed direct compression excipient.     

The Effect of Moisture on the Flowability of Pharmaceutical Excipients

The effect of moisture content on flowability of six pharmaceutical powders (microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), corn starch, and potato starch) was investigated. Powder flowability was measured using established static techniques and emerging dynamic avalanche behavior measurements. Static techniques did not provide enough resolution to clearly identify changes in flowability due to increasing powder moisture content. Avalanche time and its standard deviation showed that flowability of MCC, CMC, PVP, and potato starch decreased after a critical moisture content, flowability of corn starch increased and flowability did not significantly change for HPMC. The moisture decreased flowability by forming stronger interparticle liquid bridges and increased flowability by acting as a lubricant. The dynamic density of the celluloses and PVP decreased linearly with increasing moisture content as the particles swelled with water. The starches also swelled and decreased in dynamic density, but only after a moisture content corresponding to monolayer coverage of water around the particles was reached. As flowability and dynamic density change with moisture content, to ensure consistent production of high-quality tablets, the moisture content of the powders must be measured and controlled.     

Effect of Different Excipients on the Physical Characteristics of Granules and Tablets with Carbamazepine Prepared with Polyethylene Glycol 6000 by Fluidized Hot-Melt Granulation (FHMG)

The objective of this study was to investigate the properties of granules and tablets with carbamazepine which were prepared employing a fluidized hot-melt granulation (FHMG) technique. The FHMG process was carried out at 65°C. Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the granulated mass. Granules containing up to 70% (w/w) of the drug and 20–90% (w/w) of a filler (lactose, mannitol, calcium hydrogen phosphate (Di-Cafos), pregelatinized starch, and microcrystalline cellulose (MCC)) were produced. When the drug content was 30% (w/w), the yield of the process was satisfying (>95%) and flowability of the granules was better than placebo granules or drug-loaded granules prepared by wet granulation. Type of a filler had strong impact on physical properties of granules, and size distribution of the particles was the most homogenous when lactose or Di-Cafos were used. The FHMG technique enabled preparation of granules with better compressability compared with the wet-granulated product or with non-granulated powders. Tablets with shorter disintegration time than 10 min were obtained with 2.0% crospovidone added as a disintegrant. In comparison to tablets prepared from the wet-granulated mass, employment of the FHMG method resulted in tablets with faster dissolution of carbamazepine (more than 80% of the drug released within 15 min). This was achieved with mannitol or lactose/MCC, as fillers.     

小豆抗性淀粉含量及蒸煮后硬度分析

本文利用国内140个红小豆种质资源,探究其抗性淀粉含量与蒸煮后硬度的地域分布特征,分析蒸煮后硬度与营养指标的相关性,同时筛选抗性淀粉含量高与蒸煮后硬度低的种质资源,结果表明：140份红小豆抗性淀粉的平均含量为14.25 %,蒸煮后硬度的平均值为150.72 g。吉林地区红小豆抗性淀粉含量最高,为15.71 %;内蒙古地区红小豆蒸煮后硬度最低,为96.42 g。抗性淀粉与总淀粉之间呈极显著负相关;蒸煮后硬度与抗性淀粉之间呈显著正相关,但与总淀粉及蛋白质之间无显著相关。筛选出12份抗性淀粉含量>17.83 %的优异红小豆种质资源,可用于糖尿病人专用品种的选育及产品开发;9份蒸煮后硬度<76.48 g的优异红小豆种质资源可用于豆饭、豆粥产品的开发。     

Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression

Orally disintegrating tablets (ODTs) are challenged by the need for simple technology to ensure good mechanical strength coupled with rapid disintegration. The objective of this work was to evaluate microwave-assisted development of ODTs based on simple direct compression tableting technology. Placebo ODTs comprising directly compressible mannitol and lactose as diluents, super disintegrants, and lubricants were prepared by direct compression followed by exposure to >97% relative humidity and then microwave irradiation for 5 min at 490 W. Placebo ODTs with hardness (>5 kg/cm²) and disintegration time (<60 s) were optimized. Palatable ODTs of Lamotrigine (LMG), which exhibited rapid dissolution of LMG, were then developed. The stability of LMG to microwave irradiation (MWI) was confirmed. Solubilization was achieved by complexation with beta-cyclodextrin (β-CD). LMG ODTs with optimal hardness and disintegration time (DT) were optimized by a 2³ factorial design using Design Expert software. Taste masking using sweeteners and flavors was confirmed using a potentiometric multisensor-based electronic tongue, coupled with principal component analysis. Placebo ODTs with crospovidone as a superdisintegrant revealed a significant increase in hardness from ～3 to ～5 kg/cm² and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/cm², DT?<?30s, and rapid dissolution of LMG, and good stability was optimized by DOE and the design space derived. While β-CD complexation enabled rapid dissolution and moderate taste masking, palatability, which was achieved including flavors, was confirmed using an electronic tongue. A simple step of humidification enabled MWI-facilitated development of ODTs by direct compression presenting a practical and scalable advancement in ODT technology.     

Chemometric evaluation of pharmaceutical properties of antipyrine granules by near-infrared spectroscopy

The purpose of this research was to apply near-infrared (NIR) spectroscopy with chemometrics to predict the change of pharmaceutical properties of antipyrine granules during granulation by regulation of the amount of water added. The various kinds of granules (mean particle size, 70–750 μm) were obtained from the powder mixture (1 g of antipyrine, 6 g of hydroxypropylcellulose, 140 g of lactose, and 60 g of potato starch) by regulation of the added water amount (11–19 wt/wt%) in a high-speed mixer. The granules were characterized by mean particle size, angle of repose, compressibility, tablet porosity, and tablet hardness as parameters of pharmaceutical properties. To predict the pharmaceutical properties, NIR spectra of the granules were measured and analyzed by principal component regression, (PCR) analysis. The mean particle size of the granules increased from 81 μm to 650 μm with an increase in the amount of water, and it was possible to make larger spherical granules with narrow particle size distribution using a high-speed mixer. Angle of repose, compressibility, and porosity of the tablets decreased with an increase of added water, but tablet hardness increased. The independent calibration models to evaluate particle size, angle of repose, and tablet porosity and hardness were established by using PCR based on NIR spectra of granules, respectively. The correlation coefficient constants of calibration curves for prediction of mean particle size, angle of repose, tablet porosity, and tablet hardness were 0.9109, 0.8912, 0.7437, and 0.8064, respectively. It is possible that the pharmaceutical properties of the granule, such as mean particle size, angle of repose, tablet porosity, and tablet hardness, could be predicted by an NIR-chemometric method.     

Roller Compaction, Granulation and Capsule Product Dissolution of Drug Formulations Containing a Lactose or Mannitol Filler, Starch, and Talc

This study investigated the influence of excipient composition to the roller compaction and granulation characteristics of pharmaceutical formulations that were comprised of a spray-dried filler (lactose monohydrate or mannitol), pregelatinized starch, talc, magnesium stearate (1% w/w) and a ductile active pharmaceutical ingredient (25% w/w) using a mixed-level factorial design. The main and interaction effects of formulation variables (i.e., filler type, starch content, and talc content) to the response factors (i.e., solid fraction and tensile strength of ribbons, particle size, compressibility and flow of granules) were analyzed using multi-linear stepwise regression analysis. Experimental results indicated that roller compacted ribbons of both lactose and mannitol formulations had similar tensile strength. However, resulting lactose-based granules were finer than the mannitol-based granules because of the brittleness of lactose compared to mannitol. Due to the poor compressiblility of starch, increasing starch content in the formulation from 0% to 20% w/w led to reduction in ribbon solid fraction by 10%, ribbon tensile strength by 60%, and granule size by 30%. Granules containing lactose or more starch showed less cohesive flow than granules containing mannitol and less starch. Increasing talc content from 0% to 5% w/w had little effect to most physical properties of ribbons and granules while the flow of mannitol-based granules was found improved. Finally, it was observed that stored at 40 °C/75% RH over 12 weeks, gelatin capsules containing lactose-based granules had reduced dissolution rates due to pellicle formation inside capsule shells, while capsules containing mannitol-based granules remained immediate dissolution without noticeable pellicle formation.     

Effect of polymorphic form on the functional properties of cellulose: A comparative study

The powder and tableting properties of cellulose II powders (MCCII) and (SDCII) were evaluated and compared with common direct compression binders. The cellulose II polymorphs offered more benefits in terms of functionality as compared with cellulose I (Avicel^® PH-102) spray dried lactose and starch. Spray dried cellulose II (SDCII) had a better disintegrant ability, but a lower compactibility than microcrystalline cellulose I (Avicel^® PH-102). However, when mixed and compressed with acetaminophen, SDCII was as compactable as cellulose I. Further, unprocessed cellulose II has a comparable compressibility to that of cellulose I. SDCII was found to be less friable, less sensitive to magnesium stearate, and possessed better acetaminophen loading capacity than unprocessed cellulose II and comparable to that of cellulose I. The cellulose II materials showed potential for use as a direct compression excipient.     

Powder and mechanical properties of microcrystalline cellulose with different degrees of polymerization

This study investigated the influence of the degree of polymerization (DP) of cellulose materials (microcrystalline cellulose [MCC]) on some powder properties and the compression behavior of these materials. The DP was determined by measurements of viscosity (H). The weight average of molecular weight and the weight average of the different DPs were investigated after MCC was modified to cellulose tricarbanilate by light scattering measurements. The DP showed a remarkable influence on the physicochemical properties of the cellulose materials and, consequently, on the behavior of these materials during compression. MCC types with a high DP value showed greater water absorption than the types with a low DP value. No relevant relationship between the crystallinity index and the DP could be observed. DP 190 showed lower compactibility and compressibility parameters than DP 244 and 299. No significant differences could be observed between DP 244 and 299 when the same particle size fraction was compressed. Furthermore, the compressibility was increased by increasing the DP.     

Influence of Formulation Factors on Tablet Formulations with Liquid Permeation Enhancer Using Factorial Design

For a drug with low bioavailability, a matrix tablet with liquid permeation enhancer (Labrasol®) was formulated. Factorial design was used to evaluate the effect of three formulation factors: drug percentage, polymer type (Methocel® K100M or Eudragit® L 100-55), and tablet binder percentage (Plasdone® S-630) on tablet characteristics. Tablets were prepared by direct compression and characterized. Compressibility index values ranged between 15.90% and 29.87% and tablet hardness values from 7.8 to 29.78 Kp. Eudragit®-containing formulations had better compressibility index values with higher tablet hardness. Time for 75% of drug release (T ₇₅) was calculated, and formulations containing Eudragit® L 100-55 had faster release rates than tablet formulations with Methocel® K100M. Formulations with Methocel® K100M fit well in the Higuchi model as indicated by their R ² values (>0.98). Among all the formulation factors studied, polymer type displayed the highest and statistically significant effect on compressibility index, tablet hardness, and dissolution rate. Statistical design helped in better understanding the effect of formulation factors on tablet characteristics important for designing formulations with desired characteristics.     

Temperature-sensitive binding of alpha-glucans by Bacillus stearothermophilus.

Bacillus stearothermophilus was found to bind strongly to starch and related alpha-glucans at 25 degrees C but not at 55 degrees C. The binding at the lower temperature could be assayed either by binding of fluorescein-labeled amylopectin to washed cell suspensions or through the reversible retention of bacteria by affinity chromatography in matrices containing immobilized starch. The bacteria exhibited amylopectin-dependent agglutination. The binding and agglutination were highest in bacteria grown on substrates containing alpha-1,4-glucosidic linkages such as maltose or dextrins. The binding affinity of cells was highest for maltohexaose, lower for maltose, and low or undetectable for glucose, isomaltose, cellobiose, or lactose. The reduced binding at the higher temperature was due to the rapid breakdown of the alpha-glucosides. The bacteria exhibited an extracellular alpha-amylase activity as well as a cell-associated alpha-glucosidase with high activity at 55 degrees C but undetectable activity at 25 degrees C. The inducibility, specificity, and protease sensitivity of the thermophilic alpha-glucosidase in whole cells were similar to those of the binding activity assayed at the lower temperature. Further evidence linking the binding and alpha-glucosidase activities came from a mutant, selected through affinity chromatography, which was reduced in starch binding at room temperature and also reduced in membrane-associated alpha-glucosidase activity at 55 degrees C. These results suggest a novel survival mechanism whereby a bacterium attaches to a macromolecular substrate under nonoptimal growth conditions for possible utilization upon a shift to more favorable conditions.     

Selected Physical and Chemical Properties of Feverfew (<Emphasis Type="BoldItalic">Tanacetum parthenium</Emphasis>) Extracts Important for Formulated Product Quality and Performance

The objectives of this research are: (1) to assess selected formulation-relevant physical properties of several commercial Feverfew extracts, including flowability, hygroscopicity, compressibility and compactibility (2) to develop and validate a suitable extraction method and HPLC assay, and (3) to determine the parthenolide content of several commercial Feverfew extracts. Carr’s index, minimum orifice diameter and particle-particle interaction were used to evaluate powder flowability. Hygroscopicity was evaluated by determining the equilibrium moisture content (EMC) after storage at various % relative humidities. Heckle analysis and compression pressure-radial tensile strength relationship were used to represent compression and compaction properties of feverfew extracts. An adapted analytical method was developed based on literature methods and then validated for the determination of parthenolide in feverfew. The commercial extracts tested exhibited poor to very poor flowability. The comparatively low mean yield pressure suggested that feverfew extracts deformed mainly plastically. Hygroscopicity and compactibility varied greatly with source. No commercial feverfew extracts tested contained the label claimed parthenolide. Even different batches from the same manufacturer showed significantly different parthenolide content. Therefore, extract manufactures should commit to proper quality control procedures that ensure accurate label claims, and supplement manufacturers should take into account possible differences in physico-chemical properties when using extracts from multiple suppliers.     

Tablet formulation containing meloxicam and beta-cyclodextrin: mechanical characterization and bioavailability evaluation

The purpose of this research was to evaluate beta-cyclodextrin (beta-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of beta-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of beta-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A(L)-type diagram with inclusion complex of 1:1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formulations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of beta-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C(max), K(e), and area under the curve [AUC](0-infinity)) were significantly increased in presence of beta-CD. These results suggest that beta-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, beta-CD is particularly useful for improving the oral bioavailablity of meloxicam.     

The Effects of Fillers and Binders on the Accuracy of Tablet Subdivision

The effects of excipients on the accuracy of tablet subdivision are severely underinvestigated. In this study, placebo tablets were prepared using a combined mixture design of fillers and binders to evaluate the effect of these excipients on subdivision accuracy. The responses assessed were mass loss, mass variation, tablet fragmentation, and increased friability. Dicalcium phosphate dihydrate (DCP) gave rise to more uniform and denser tablets than microcrystalline cellulose (MCC), thus resulting in greater subdivision accuracy. The binder type, hydroxypropylcellulose (HPC) or polyvinylpyrrolidone (PVP), did not affect the subdivision of DCP tablets. On the contrary, the structural similarity between HPC and MCC led to improved subdivision accuracy for MCC tablets. A less accurate subdivision was observed in tablets prepared with a DCP–MCC combination; this finding could be attributed to irregular binder distribution in this matrix. An optimized response was built using desirability analysis. This study helps to illuminate the relationship between fillers and binders to guide formulation scientists in the development of tablets with better subdivision performance.     

Carbohydrate binding activities of Bradyrhizobium japonicum. I. Saccharide-specific inhibition of homotypic and heterotypic adhesion

Bradyrhizobium japonicum (R110d) exhibited four saccharide-specific binding activities: (a) adsorption to Sepharose beads containing covalently coupled lactose; (b) homotypic agglutination through one pole of the cell (star formation); (c) heterotypic adhesion to the cultured soybean cell line, SB-1; and (d) attachment to roots of soybean plants. Each of these binding activities can be inhibited by the addition of galactose or lactose, but not by derivatives such as N-acetyl-D-galactosamine or melibiose. Treatment of wild-type bacteria with N-methyl-N'-nitro-N-nitrosoguanidine followed by selection on the basis of reduced binding to SB-1 cells, resulted in two specific mutants, designated N4 and N6. Compared to wild type, these two mutants also exhibited decreased binding activity in: (a) adsorption to lactose-Sepharose beads; (b) homotypic star formation; and (c) heterotypic attachment to roots of soybeans plants. These results suggest that all four of the saccharide-inhibitable binding activities of Bradyrhizobium japonicum may be mediated by the same mechanism(s) or molecular component(s).     

The mechanism of inducer exclusion. Direct interaction between purified III of the phosphoenolpyruvate:sugar phosphotransferase system and the lactose carrier of Escherichia coli

A hypothesis for the regulation of some sugar transport systems by the bacterial phosphoenolpyruvate:sugar transport system postulates an interaction between III^Glc of this system and the carrier whose activity is regulated. We have studied this interaction in more detail, employing one of these transport systems, the lactose carrier of Escherichia coli. Purified III^Glc of the phosphotransferase system interacted directly with the lactose carrier. The binding of III^Glc to lactose carrier required the presence of the non-phosphorylated form of III^Glc and substrates of the carrier and exhibited a stoichiometry of 1.2± 0.2 mol III^Glc/mol lactose carrier. The K_d of lactose carrier for III^Glc was 10 ± 5 µM. III^Glc is apparently unable to interact with a mutant lactose carrier which still binds but does not transport galactosides. The binding of III^Glc to the lactose carrier results in a 3.5-fold increase in the apparent affinity of galactosides for the carrier. Significantly, the binding of III^Glc to the lactose carrier results in an inhibition of galactoside translocation both in membrane vesicles and liposomes reconstituted with the purified lactose carrier. This inhibition may thus be the basis for the well-documented phenomenon of inducer exclusion.     

Separation of bovine heart galactose lectin from endogenous glycoproteins co-purified with the lectin during affinity chromatography

During affinity chromatographic purification of bovine heart 14 kDa galactose-binding lectin (galectin 1) on lactose-Sepharose, several high molecular weight non-lectin glycoproteins were co-purified with the lectin. Glycoprotein binding to the affinity matrix was neither hydrophobic nor ionic, but galactose-dependent since lactose abolished binding. Purification of galectin from the co-purified glycoproteins by affinity electrophoresis in presence of the specific sugar lactose increased agglutination activity about 65-fold, indicating that a complex containing galectin molecules bound sugar specifically to endogenous glycoproteins with sugar binding sites still available had been retained on lactose-Sepharose.     

Direct pelletization in a rotary processor controlled by torque measurements. III. Investigation of microcrystalline cellulose and lactose grade

The aim of the present study was to investigate the use of different grades of microcrystalline cellulose (MCC) and lactose in a direct pelletization process in a rotary processor. For this purpose, a mixed 2- and 3-level factorial study was performed to determine the influence of the particle size of microcrystalline cellulose (MCC), (≈60 and 105 μm) and lactose (≈30, 40, and 55 μm), as well as MCC type (Avicel and Emcocel) on the pelletization process and the physical properties of the prepared pellets. A 1∶4 mixture of MCC and lactose was applied, and granulation liquid was added until a 0.45 Nm increase in the torque of the friction plate was reached. All combinations of the 3 factors resulted in spherical pellets of a high physical strength. The particle size of MCC was found to have no marked effect on the amount of water required for agglomerate growth or on the size of the resulting pellets. An increasing particle size of lactose gave rise to more spherical pellets of a more narrow size distribution as well as higher yields. The MCC type was found to affect both the release of the model drug from the prepared pellets and the size distribution. Generally, the determined influence of the investigated factors was small, and direct pelletization in a rotary processor was found to be a robust process, insensitive to variations in the particle size and type of MCC and the particle size of lactose. Published: October 24, 2005     

Thermodynamic analysis of the binding of galactose and poly-N-acetyllactosamine derivatives to human galectin-3.

Galectin-3, with a wide tissue distribution and marked developmental regulation, provides significant insights into the progression of various disease and developmental stages. Recognized by its specificity for galactose, a detailed characterization of its sugar binding ability has been investigated by isothermal titration calorimetry. The results presented here complement well with the earlier studies utilizing hapten inhibition assays. Among the various lactose derivatives studied, A-tetrasaccharide emerged with the highest affinity for binding to galectin-3 combining site. This blood group saccharide exhibited a binding affinity 37-fold higher and a 102 kJ/mol more favorable change in enthalpy over lactose at 280 K indicating the existence of additional subsites for both the alpha1-3-linked N-acetylgalactosamine at the non-reducing end and the alpha1-2-linked L-fucosyl residue. The thermodynamic parameters evaluated for other ligands substantiate further the carbohydrate recognition domain to be part of an extended binding site. Binding thermodynamics of galectin-3 with the galactose derivatives are essentially enthalpically driven and exhibit compensatory changes in DeltaH degrees and TDeltaS owing to solvent reorganization.