Physical properties and compact analysis of commonly used direct compression binders

This study investigated the basic physico-chemical property and binding functionality of commonly used commercial direct compression binders/fillers. The compressibility of these materials was also analyzed using compression parameters derived from the Heckel, Kawakita, and Cooper-Eaton equations. Five classes of excipients were evaluated, including microcrystalline cellulose (MCC), starch, lactose, dicalcium phosphate (DCP), and sugar. In general, the starch category exhibited the highest moisture content followed by MCC, DCP, lactose, and finally sugars; DCP displayed the highest density, followed by sugar, lactose, starch, and MCC; the material particle size is highly processing dependent. The data also demonstrated that MCC had moderate flowability, excellent compressibility, and extremely good compact hardness; with some exceptions, starch, lactose, and sugar generally exhibited moderate flowability, compressibility, and hardness; DCP had excellent flowability, but poor compressibility and hardness. This research additionally confirmed the binding mechanism that had been well documented: MCC performs as binder because of its plastic deformation under pressure; fragmentation is the predominant mechanism in the case of lactose and DCP; starch and sugar perform by both mechanism.     

Antimicrobial properties of fibrous cellulose and other polymeric materials modified with chlorhexidine]

Since fibrous cellulose and other polymeric materials are widely used as dressings, it was of interest to study the mechanism of the antimicrobial action of the products from such materials physically and chemically modified by chlorhexidine, a broad spectrum antiseptic. As vehicles and prolongation agents the following products were used: dressing gauze and cation exchange derivatives of cellulose and starch i.e. monocarboxycellulose (MCC), phosphate cellulose (PC), carboxymethyl cellulose (CMC), monocarboxyl starch (MCS) and alginic acid (AA), a natural compound. It was shown that chemical attachment of chlorhexidine provided a 2-4-fold increase in the antimicrobial effect of the preparations as compared to the use of physical sorption. The antimicrobial effect of the polymeric form of chlorhexidine based on MCC and PC was much higher than that based on MCC, MCS and AA.     

Flow Behavior of Native Corn and Potato Starch Granules in Aqueous Suspensions

The flow behavior of native corn and potato starch granule suspensions prepared in a concentrated sucrose solution has been investigated. Measurements were performed using a rotational rheometer with a concentric cylinder geometry. Starch suspensions were dilute to semi-concentrated (1 % to 25 % by volume). Shear and dynamic viscosity were measured by shear flow and dynamic oscillatory testing at 20, 50 and 80 °C. The starch suspensions exhibited essentially Newtonian behavior at all solid contents, although at higher solid volume fractions there was evidence of slight shear thickening. The relative viscosity of suspensions increased with increasing starch granule content, and the data conformed well to Maron-Pierce’s equation. An increase in maximum packing fraction and gravitational depletion of the starch granules with increasing temperature resulted in lower relative viscosities at higher temperatures. Also, the relative viscosities of potato starch granule suspensions with bigger, more oval and anisometric particles were lower than those of corn starch suspensions where granules were closer to sphericity but were angular in shape. Oscillatory shear testing results showed the presence of viscoelastic properties at intermediate solid volume fractions at low frequencies; in addition, the relative shear viscosity was higher than the relative dynamic viscosity, probably due to the formation of shear-induced structures during the shear flow test.     

Carboxymethylcellulose and hydroxypropylmethylcellulose as additives in reduction of oil content in batter based deep-fat fried boondis

Studies on boondi, a deep fried batter based legume snack food popular in the Indian sub-continent were conducted to reduce oil content. Effects of varying the water levels in the batter on the shape of the resulting boondi were noted. The effects of incorporating carboxymethyl cellulose (CMC) and hydro-xypropylmethyl cellulose (HPMC) in the bengal gram flour on the water levels so as to get appropriate batter viscosity for getting round shaped boondi were also recorded. The addition of 2% CMC and 1% HPMC (based on weight of bengal gram flour) in the dough decreased oil content in the fried boondi by 26.2% and 22.7% respectively as compared to the control.     

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.     

一种基于胶体微晶纤维素的改良病毒蚀斑测定法的建立与评价北大核心CSCD

胶体微晶纤维素(avicel)是一种由微晶纤维素(microcrystalline cellulose, MCC)和羧甲基纤维素(carboxymethyl cellulose,CMC)制成的混合物,可用于病毒蚀斑测定。常用的avicel由FMC公司生产,其MCC和CMC比例相对固定,无法很好地适应所有类型病毒的蚀斑测定实验。本研究通过对比不同的MCC和CMC配制比例对avicel在病毒蚀斑测定作用的影响,建立了一种操作简便、实用性好和稳定性好的改良avicel病毒蚀斑测定法。为了配制不同浓度MCC和CMC的混合物,本研究制备出12种2×avicel覆盖层,测定其总体黏度及底层黏度,评估其与传统覆盖层相比,使用时的操作难易程度。进一步将12种2×avicel覆盖层制备成avicel-DMEM营养覆盖层,测定96孔板中猪流行性腹泻病毒滴度,比较12种avicel覆盖层及传统覆盖层蚀斑大小、清晰度、稳定性及滴度准确性等的差异,筛选出最佳测定方法。结果显示,12种2×avicel覆盖层中,除4.8%MCC+1.4%CMC和4.8%MCC+1.0%CMC外,其余2×avicel覆盖层在实际使用中均比2×CMC覆盖层更容易吸取和配制营养覆盖层。最后,利用avicel病毒蚀斑测定法测定96孔板中猪流行性腹泻病毒滴度,结果显示CMC浓度越高蚀斑越小,其中终浓度为0.6%MCC+0.7%CMC的avicel覆盖层测定蚀斑染色最清晰,准确度与传统覆盖层相似,但操作较传统覆盖层更简便。综上所述,本研究建立了一种操作简便、实用性好和稳定性好的改良avicel病毒蚀斑测定法,为病毒的病原学、抗病毒药物及疫苗等相关研究的展开提供了良好的实验基础。     

Spray-Dried Cellulose Nanofibers as Novel Tablet Excipient

The purpose of this study was to evaluate the potential of cellulose nanofibers (also referred as microfibrillated cellulose, nanocellulose, nanofibrillated, or nanofibrillar cellulose) as novel tabletting material. For this purpose, physical and mechanical properties of spray-dried cellulose nanofibers (CNF) were examined, and results were compared to those of two commercial grades of microcrystalline cellulose (MCC), Avicel PH101 and Avicel PH102, which are the most commonly and widely used direct compression excipients. Chemically, MCC and CNF are almost identical, but their physical characteristics, like mechanical properties and surface-to-volume ratio, differ remarkably. The novel material was characterized with respect to bulk and tapped as well as true density, moisture content, and flow properties. Tablets made of CNF powder and its mixtures with MCC with or without paracetamol as model compound were produced by direct compression and after wet granulation. The tensile strength of the tablets made in a series of applied pressures was determined, and yield pressure values were calculated from the measurements. With CNF, both wet granulation and direct compression were successful. During tablet compression, CNF particles were less prone to permanent deformation and had less pronounced ductile characteristics. Disintegration and dissolution studies showed slightly faster drug release from direct compression tablets with CNF, while wet granulated systems did not have any significant difference.     

Extrusion processing of high amylose potato starch materials

Thermoplastic starch was prepared by mixing native high amylose potato starch and normal potato starch in a Buss co-kneading extruder at starch to glycerol ratios of 100:45 and 100:30. The materials were also conditioned to different moisture contents at different relative humidities at 23 °C. After the mixing, the compounds were extruded into sheets with a Brabender laboratory extruder. The thermoplastic high amylose materials exhibited a higher melt viscosity than the normal potato starch materials when conditioned at 53% relative humidity. Increasing the moisture content in HAP from 27% to 30% (by weight) lowered the melt viscosity to the same level as that of normal potato starch with a moisture content of 28%. In general, the high amylose materials were more difficult to extrude than the thermoplastic material based on normal starch. The main extrusion problems encountered with the high amylose starch were unstable flow, insufficient melt tenacity and clogging of the die. By increasing the moisture content, increasing the compression ratio of the screw and increasing the rotation rate of the screw, the problems were reduced or eliminated. However, only with a starch to glycerol ratio of 100:45 was an acceptable extrusion result obtained. Extruded sheets of such high amylose materials had a stress at break of about 5 MPa at room temperature and 53% relative humidity, whereas the corresponding value for normal potato (thermoplastic) starch was 3 MPa. The elongation at break was also higher in the case of the high amylose material. The results are discussed in terms of residual crystallinity of the starch materials.     

Effect of hydrophilic swellable polymers on dissolution enhancement of carbamazepine solid dispersions studied using response surface methodology

The objective of this work was to study dissolution enhancement efficiency and solid dispersion formation ability of hydrophilic swellable polymers such as sodium carboxymethyl cellulose (Na-CMC), sodium starch glycolate (SSG), pregelatinized starch (PGS), and hydroxypropylmethyl cellulose (HPMC) with carbamazepine using 3² full factorial design for each of the polymers. Solid dispersions of carbamazepine were prepared using solvent evaporation method with around 70% solvent recovery. The independent variables were the amount of polymer and organic solvent. The dependent variables assessed were percentage drug dissolved at various time points and dispersion efficiency (ie, in terms of particle size of solid dispersion). Solid dispersions were evaluated for percentage drug dissolved, wettability, differential scanning calorimetry, scanning electron microscopy, and angle of repose. Multiple linear regression of results obtained led to equations, which generated contour plots to relate the dependent variables. Similarity factor and mean dissolution time were used to compare dissolution patterns obtained in distilled water and simulated gastric fluid United States Pharmacopeia (USP) XXVI of pH 1.2. Maximum drug dissolution was obtained with polymer order Na-CMC>SSG>PGS>HPMC. Particle size of drug was reduced ≈ 10–15, 3–5, 5–7, and 10–25 times in Na-CMC, SSG, PGS, and HPMC solid dispersions, respectively; whereas wettability of solid dispersions was found in the order of Na-CMC>HPMC>PGS>SSG. Angle of repose was found to be in the range of 29° to 35° for all solid dispersions, which shows good flowability characteristics. HPMC showed increase in drug dissolution up to an optimized level; however, furthers increase in its concentration decreased drug dissolution. Published: April 6, 2007     

'Green' crosslinking of native starches with malonic acid and their properties

Starch is a highly hydrophilic biomaterial with weak mechanical properties rendering it useless for commercial applications. A fully 'green' water based process is presented to crosslink corn (cereal) and potato (tuber) starch to enhance mechanical properties as well as lower hydrophilicity. In addition, malonic acid, a green, plant based water soluble and relatively inexpensive polycarboxylic acid, was used as the crosslinker. The reactivity of potato starch toward esterification and crosslinking was found to be higher than that of corn starch owing to the inherent differences in the granule morphology and internal structure of the two starches. It was observed that potato starch granules had a higher degree of substitution (DS) of 0.19 than corn starch granules (DS=0.1) under similar reaction conditions. Chemical, thermal and mechanical test results confirmed the crosslinking as well as reduced moisture sensitivity.     

Edible films made from natural resources; microcrystalline cellulose (MCC), methylcellulose (MC) and corn starch and polyols-Part 2

Aqueous blends of microcrystalline cellulose (MCC) or methyl cellulose (MC) and corn starch with or without polyols were extruded, hot pressed and studied, after their conditioning at different relative humidities, in terms of their thermal, mechanical and water and gas permeability properties. An increase in water or polyol content showed a considerable increase in percentage elongation but also a decrease in the tensile strength of films. The presence of high cellulose contents increased the tensile strength and decreased the water vapour transmission of films. The development of crystallinity with time resulted in a decrease of both gas and water permeability. Several semiempirical models for calculation of gas permeability and tensile strength and tensile and flexural moduli were applied. The obtained values were compared to those experimentally determined and with the ones reported in the literature. On several occasions, quite significant discrepancies were found which were attributed to differences in molecular weight, percentage crystallinity and polymorphism.     

Sorption of Monoterpenoids and Sesquiterpenoids by Natural Polysaccharides

Sorption of terpenoids (essential oil components) from aqueous solutions by six types of native food starches was studied by capillary gas chromatography. Sorption of volatile substances did not depend on amylose content in starch and specific surface of its granules. The degree of sorption was maximum (86%) for corn starch containing 25–28% amylose and decreased in the following order: tapioca starch (77%) > potato starch (74%) > wheat starch (70%) > high-amylose corn starch (58%) > amylopectin corn starch (57%). Amylopectin corn starch differed from other starches in the mechanism of sorption and selectivity to compounds with various functional groups.     

Sorption of mono- and sesquiterpenes by natural polysaccharides

Sorption of terpenoids (essential oil components) from aqueous solutions by six types of native food starches was studied by capillary gas chromatography. Sorption of volatile substances did not depend on amylose content in starch and specific surface of its granules. The degree of sorption was maximum (86%) for corn starch containing 25-28% amylose and decreased in the following order: tapioca starch (77%) > potato starch (74%) > wheat starch (70%) > high-amylose corn starch (58%) > amylopectin corn starch (57%). Amylopectin corn starch differed from other starches in the mechanism of sorption and selectivity to compounds with various functional groups.     

Molecular fractionation of starch by density-gradient ultracentrifugation

Amylose and amylopectin in corn and potato starches were fractionated by centrifugation at 124,000g for 3-72 h at 40 degrees C in a gradient media, Nycodenz, based on their sedimentation rate differences. The fractions were collected from a centrifuge tube, and then analyzed by the phenol-sulfuric acid method and iodine-binding test. Amylopectin, a large and highly branched starch molecule, migrated faster than amylose and quickly reached its isopycnic point with a buoyant density of about 1.25 g/mL, exhibiting a sharp and stable carbohydrate peak. Amylose, which is a relatively small and linear molecule, however, migrated slowly in a broad density range and continued moving to higher density regions, eventually overlapping with amylopectin peak as the centrifugation continued. This could indicate that the buoyant density of amylose is similar to that of amylopectin. Under centrifugal conditions of 3 h and 124,000g, amylose and amylopectin molecules were clearly separated, and the presence of intermediate starch molecules (11.5 and 7.7% for corn and potato starch, respectively) was also observed between amylose and amylopectin fractions. The amylose content of corn and potato starches was 22.6 and 21.1%, respectively, based on the total carbohydrate analysis after the ultracentrifugation for 3 h. In alkaline gradients (pH 11 or 12.5), the sedimentation rate of starch molecules and the buoyant density of amylopectin were reduced, possibly due to the structural changes induced by alkali.     

Development of Beauveria bassiana dry formulation for vectoring by honey bees Apis mellifera (Hymenoptera: Apidae) to the flowers of crops for pest control

Using bee pollinators as a means for the dissemination of microbial control agents, such as Beauveria bassiana, against insect pests of agricultural crops is a novel and interesting approach to biological control. In four laboratory trials, one in Canada and three in Jordan, factors affecting the acquisition of B. bassiana by honey bees were evaluated using hive-mounted inoculum dispensers. The numbers of conidia carried by bees emerging from the dispensers differed according to the type of carrier used. Bees that passed through corn flour acquired more inoculum than did those that walked through wheat flour, durum semolina, corn meal, potato starch, potato flakes, oat flour or barley flour. The numbers of conidia acquired by the bees increased with decreasing particle size and moisture content of the carrier, and with increasing density of B. bassiana conidia in the formulation. Time required for a bee to pass through the dispenser did not significantly affect the acquisition of conidia. This study indicated that honeybees (Apis mellifera carnica) have a great potential for vectoring B. bassiana in crop systems. It also opens more avenues for studies on bee delivery of other microbial biological control agents.     

Influence of bulk and tapped density on the determination of the thermal conductivity of powders and blends

The aim of this study was to evaluate a non-steady-state needle sensor to determine the thermal conductivity (lambda) of powders and their blends. It was investigated how lambda of different powders was influenced by (1) bulk vs tapped density, (2) moisture content of the powders, and (3) blending time of the powders. Different powders were evaluated: 2 lactose powders with different properties, a microcrystalline cellulose powder, a cornstarch powder, and 3 herbal extracts. The results show that the values of lambda are highly dependent on the bulk and tapped density of the powders. Bulk density measurements were generally not sensitive enough to detect the moisture content within a powder. The tapped density measurements were reliable and highly reproducible and could differentiate between the nature of a powder and the powder moisture content. Measurements of lambda were able to be used to monitor the powder blending process. To be able to use thermal conductivity measurements to characterize powder properties in quality control, the powder density must be defined because changes in density affect lambda. Using thermal conductivity as a measure for process analytical technology seems to be feasible and can add valuable information to the process under investigation.     

Structural Changes in Starch Granules of Low Moisture Content during Heating

The thermal behavior of the starch structure was determined successfully under low moisture conditions by differential thermal analysis (DTA) using an anti-leak cell (resistant to an internal pressure of about 40 kg/cm²). Three kinds of starch, potato, kuzu and corn, with a low moisture content less than 12% indicated two strong endothermic peaks, one at the lower temperature (A) and the other at the higher temperature (B) in a temperature range approximately from 20 to 250°C. From microscopic observations and determinations of intrinsic viscosity, blue value and the solubility of heated starch, it is considered that peak A reflects an endothermic process accompanied by dextrinization involving the collapse of the ordered structure of starch with a limited breakdown in the polysaccharide chain. On the other hand, peak B corresponds to a thermal decomposition of the glucosyl residues, that is caramelization. The temperature at which such dextrinization takes place is markedly influenced by both the starch species and the moisture content of the starch.     

Interpretation of small angle x-ray scattering from starch on the basis of fractals

Using small-angle X-ray scattering, the behaviour of corn and potato starches during gelatinization, swelling, and rétrogradation was investigated. The scattering patterns were analysed on the basis of the fractal concept. The main scattering source from low moisture starches could be interpreted as a ‘surface fractal’ obeying a power law with an exponent of ca —4. When the starch swelled, the surface fractal characteristic was recognised only at very low angles, and on heating it disappeared at ca 80 °C. For gelatinised starches, the whole scattering pattern obeyed the power law with the power around -2.0. This result suggests that the physical arrangement of gelatinised starch molecules is a ‘mass fractal’, i.e. a self-similar structure, in nature. Further, it was found that the scattering of the retrograded starch showed a shoulder like peak superimposed the background scattering representing the mass fractal. The corresponding Bragg spacing was estimated to be 31˜15nm.     

Molecular dynamic studies of the compatibility of some cellulose derivatives with selected ionic liquids

Molecular dynamics techniques were used to study oligomers that mimic cellulose and various derivatives in the amorphous phase, including cellulose (C), methyl cellulose (MC), hydroxypropyl cellulose (HPC), and carboxymethyl cellulose (CMC). Densities and solubility parameters were determined for a series of oligomers with increasing chain length. Both properties were found to change linearly with the degree of polymerization (from monomers to dodecamers). Extrapolated predictions of the densities (g/cm³) for long chain polymers are: C, 1.42; MC, 1.33; HPC, 1.30; and CMC, 1.42. Computed values for the solubility parameter (MPa^1/2) are: C, 25.39; MC, 21.43; HPC, 21.70; and CMC, 24.35. We also evaluated the sensitivity of the solubility parameter to changes in the calculated density and found the dependence to be significant. The calculated solubility parameters were evaluated against experimental and other theoretical values as well as against selected ionic liquids comprised of cations in the imidazolium family and the chloride and trifluoroacetate anions.     

Internal structure and physicochemical properties of corn starches as revealed by chemical surface gelatinization

The organization of amylose and amylopectin within starch granules is still not well elucidated. This study investigates the radial distribution of amylose and amylopectin in different corn starches varying in amylose content (waxy corn starch (WC), common corn starch (CC), and 50% and 70% amylose corn starches (AMC)). Corn starches were surface gelatinized by 13 M LiCl at room temperature to different extents (approximately 10%, 20%, 30%, and 40%). The gelatinized surface starch and remaining granules were characterized for amylose content, amylopectin chain-length distribution, thermal properties, swelling power (SP), and water solubility index (WSI). Except for the outmost 10% layer, the amylose content in CC increased slightly with increasing surface removal. In contrast, amylose was more concentrated at the periphery than at the core for 50% and 70% AMC. The proportion of amylopectin A chains generally decreased while that of B1 chains generally increased with increasing surface removal for all corn starches. The gelatinization enthalpy usually decreased, except for 70% AMC, whereas the retrogradation enthalpy relatively remained unchanged for CC but increased for WC, 50% and 70% AMC with increasing surface removal. The SP and WSI increased with increasing surface removal for all corn starches, with WC showing a significant increase in SP after the removal of the outmost 10% layer. The results of this study indicated that there were similarities and differences in the distribution of amylose and amylopectin chains along the radial location of corn starch granules with varying amylose contents. More amylose-lipid complex and amylopectin long chains were present at the periphery than at the core for amylose-containing corn starches.