Mixture Of Mannitol Research Articles

D143 潜熱蓄熱材と熱媒体オイルの直接接触凝固挙動(OS-11:凝固・融解を伴う伝熱現象とその応用(3))

The present study is investigated the direct contact solidification behavior between latent heat storage material and heat transfer oil. Purpose of this study is development of a latent heat storage system which is suggested using waste heat of temperature region (100〜200℃) as heat source from factories. Mixture of mannitol and erythritol was adopted as phase change material (PCM). To examine detailed heat exchange behavior, test section was constituted glass tube and the number of nozzle hole for injecting heat transfer oil is one. By this study, the following matters became clear. Size of injected oil droplets rise with the increasing flow of oil. Flow path is different depending on the height direction.

G061043 混合潜熱蓄熱材を充填した直接接触蓄熱槽の凝固・融解特性([G061-04]熱工学部門,一般セッション(4) : 固液相変化)

The present paper is suggested using waste heat of middle temperature region (100℃〜250℃) as heat source from factories. The purpose of this paper is comparing the melting and solidification characteristics of the mixture of mannitol and erythritol (C_M=70mass%, mannitol[70mass%]: erythritol[30mass%]) and mannitol as phase change materials (PCMs) in a direct-contact heat exchange type vessel. The experimental results show that the solidification behavior of the mixture of C_M=70mass% has a small porous area and the lower part of the porous solidification layer solidifies rapidly compared with mannitol. Furthermore as flow quantity of oil as a heat transfer medium increases, average heat release speed grows up.

Osmotic effects of NaCl on cell hydraulic conductivity of corn roots

In this study, whether the effect of salt (NaCl) stress on cell hydraulic conductivity (L(p)) is via osmotic pressure or ion toxicity and whether abscisic acid (ABA) can release the salt adverse effect were tested. Immediate effects of NaCl and ABA on root cortical cell L(p) of maize (Zea mays L.) were detected by measuring changes in half time of water exchange (T(1/2)) and turgor of individual single cells with a cell pressure probe for at least 1 h. The results showed that stepwise additions of NaCl (50 mM) significantly (P < 0.01) reduced the water permeability. One-step addition of 50 mM NaCl even more drastically decreased L(p). ABA was not able to instantaneously reverse the low water permeability induced by the salt stress. Long-term effects of NaCl, mannitol and sorbitol, and ABA on L(p) were measured for 6 days. Both NaCl and a mixture of mannitol and sorbitol, with the same osmotic strength of 0.25 MPa, significantly reduced L(p) at the early stage of the treatments. The declined L(p) in the salinized cell gradually and partially recovered after 2 days, whereas the L(p) with the mannitol and sorbitol mixture treatment was all time inhibited. With long-time treatment, ABA (500 nM) significantly (P < 0.01) increased turgor and L(p) of the NaCl-treated cells. In general, NaCl reduced water permeability of corn root cortical cells most likely by an osmotic stress. ABA could not instantaneously change water permeability of the corn root cortical cell subjected to NaCl stress; however, with long-time treatment, ABA was able to in part relieve the salt stress likely by osmotic adjustment.

Development of directly compressible powders via co-spray drying

Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility, powder hygroscopicity, flowability, and compactability. The influence of process parameters during spray drying on the compaction behaviour of drug/excipient mixtures was investigated via Heckel analysis. Erythritol, lactose, maltodextrin, and mannitol were efficient in co-spray drying with acetaminophen. However, lactose mixtures showed poor flowability. Spray dried mixtures containing mannitol and erythritol were characterised as non-hygroscopic, highly dense, and good flowing powders. Mannitol increased tablet tensile strength in contrast with the poor compactability of erythritol. Maltodextrin was selected for further experiments because it provided excellent tablet tensile strength. The use of erythritol, maltodextrin and mannitol in binary drug/excipient mixtures resulted in high process yields. Compacts of erythritol, mannitol, and maltodextrin were characterised by higher tablet tensile strength at higher spray drying temperatures due to the increased particle fragmentation of erythritol and mannitol mixtures and to the increased plastic deformation of maltodextrin formulations. A combination of erythritol, maltodextrin, and mannitol was selected for further formulation and process optimisation of co-spray dried powders for direct compression.

Evaluation of Critical Formulation Factors in the Development of a Rapidly Dispersing Captopril Oral Dosage Form

New methods of manufacture have enabled the creation of novel dosage forms with unique rapid-dispersion properties. This study combines one such technique with a statistical experimental design to develop dosage forms from captopril, an angiotensin-converting enzyme inhibitor used to treat cases of hypertensive emergency. The TheriForm™ process, a novel microfabrication technique, was used to build the dosage forms in a layer-by-layer fashion. Three key formulation factors were chosen for the design of experiments. A modified central composite design (Box-Behnken design) was used to maximize the efficiency of the experiments. A total of 13 distinct formulations were fabricated and tested, using mannitol as the bulk excipient. In addition, three replicates of the center point were tested to assess variability and experimental error. These formulations were tested for speed of dispersion (flash time), active content, hardness, friability, and moisture absorption. Regression analysis was performed to fit data responses to quadratic equations. Excellent dose accuracy (95% to 102% of target) and content uniformity (between 1.03% to 2.84%) were observed from all experimental formulation batches. As expected, the choice of powder additive (maltitol, maltodextrin, polyvinyl pyrrolidone), level of additive (2.5% to 7.5%), and saturation level of the binder liquid (45% to 65%) were all found to be significant factors for the TheriForm process. The regression analysis suggested that a rapidly dispersing dosage form of optimal physical properties would be obtained when a powder mixture of mannitol (97.5%) and maltitol (2.5%) is used at a saturation level of 45%. In conclusion, rapidly dispersing captopril oral dosage forms were successfully fabricated and tested. A wide range of physical properties, flash time, and hardness, were determined experimentally, and the effects of key formulation factors were identified.

Gas chromatographic method for detection of urinary sucralose: application to the assessment of intestinal permeability

We developed a capillary column gas chromatography (CCGC) method for the measurement of urinary sucralose (S) and three other sugar probes including, sucrose, lactulose (L) and mannitol (M) for use in in vivo studies of intestinal permeability. We compared the capillary method with a packed column gas chromatography (PCGC) method. We also investigated a possible role for sucralose as a probe for the measurement of whole gut permeability. Sample preparation was rapid and simple. The above four sugars were detected precisely, without interference. We measured intestinal permeability using 5- and 24-h urine collections in 14 healthy volunteers. The metabolism of sugars was evaluated by incubating the intestinal bacteria with an iso-osmolar mixture of mannitol, lactulose and sucralose at 37 °C for 19 h. Sugar concentrations and the pH of the mixture were monitored. The use of the CCGC method improved the detection of sucralose as compared to PCGC. The average coefficient of variation decreased from 15% to 4%. It also increased the sensitivity of detection by 200–2000-fold. The GC assay was linear between sucralose concentrations of 0.2 and 40 g/l ( r=1.000). Intestinal bacteria metabolized lactulose and acidified the media but did not metabolize sucralose or mannitol. The new method for the measurement of urinary sucralose permits the simultaneous quantitation of sucrose, mannitol and lactulose, and is rapid, simple, sensitive, accurate and reproducible. Because neither S nor M is metabolized by intestinal bacteria, and because only a tiny fraction of either sugar is absorbed, this pair of sugar probes appears to be available for absorption throughout the GI tract. Thus, the 24-h urinary concentrations of S and M, or the urinary S/M ratio following an oral dose of a sugar mixture, might be good markers for whole gut permeability.

Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone.

We attempted the development of rapid oral disintegration tablets by direct compression using co-ground mixture of D-mannitol and crospovidone. The co-ground mixture was prepared with a vibration rod mill. The tablets were formed by compression using a single punch-tableting machine after addition of the co-ground mixture to non-ground D-mannitol, crospovidone and magnesium stearate. Regarding the properties of tablets, hardness and the time of disintegration were measured. The particle diameter and specific surface area of the co-ground mixture were measured. The tablets manufactured from a physical mixture of 30% (w/w) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9 :1) with 65.5% (w/w) of non-ground mannitol, 4% (w/w) of crospovidone, and 0.5% (w/w) of magnesium stearate had good properties for rapidly disintegrating tablets in the oral cavity. They showed the hardness of 4.9 kg and disintegration time of 33 s. We found that adding co-ground mixture of D-mannitol and crospovidone is useful in enhancing hardness of the tablets that could not be achieved by addition of their individually ground mixture. The improvement in the hardness of the tablets was also observed when other saccharides and disintegrants were used. This method was proved to be applicable in the manufacture of tables of ascorbic acid, a water-soluble drug and nifedipine, a slightly water soluble drug; and the dissolution rate of nifedipine from the tablets in water was remarkably improved. The particle sizes of D-mannitol in the co-ground mixture were smaller than that of the individually ground mixture, resulting in a larger specific surface area of the co-ground mixture than that of the individually ground mixture. Therefore, it was presumed that crospovidone acted as a grinding assistant for D-mannitol in the co-grinding process, enhancing the hardness of tablets by increasing the contact area among powder particles.

Surface characterisation of freeze-dried protein/carbohydrate mixtures

In the present investigation freeze-drying of proteins (BSA or trypsin) together with various carbohydrates, i.e. lactose, sucrose, mannitol, α-cyclodextrin and dextrin, has been studied with particular emphasis on the surface composition of the freeze-dried powders. The proteins were found to be over-represented on the powder surface as compared to the bulk concentration of protein. The mechanism behind the surface accumulation is believed to be that proteins adsorb preferentially over carbohydrates to the ice/liquid interface in the frozen sample. The degree of surface accumulation depended on the carbohydrate used, and was increased in annealed samples compared to reference samples. The activity of trypsin was fairly well preserved (58–90%) in the freeze-dried powders, but depended on the carbohydrate excipient, whilst the surface composition had little effect on the activity. The activity preservation was improved when the protein concentration was raised from 1 to 10% in the solids. The surface composition of powders containing mixtures of mannitol and dextrin as excipients depended on the ratio between the two carbohydrates, with the lowest surface coverage of protein obtained in 50/50 mixtures.

The Physical State of Mannitol after Freeze-Drying: Effects of Mannitol Concentration, Freezing Rate, and a Noncrystallizing Cosolute

The objectives of this study were to (1) measure the effects of freezing rate and mannitol concentration on the physical state of freeze-dried mannitol when mannitol is present as a single component, (2) determine the relative concentration threshold above which crystalline mannitol can be observed by X-ray powder diffraction in the freeze-dried solid when a variety of noncrystallizing solutes are included in the formulation, and (3) measure the glass transition temperature of amorphous mannitol and to determine the degree to which the glass transition temperature of freeze-dried solids consisting of mannitol and a disaccharide is predicted by the Gordon–Taylor equation. Both freezing rate and mannitol concentration influence the crystal form of mannitol in the freeze-dried solid when mannitol is present as a single component. Slow freezing of 10% (w/v) mannitol produces a mixture of the α and β polymorphs, whereas fast freezing of the same solution produces the δ form. Fast freezing of 5% (w/v) mannitol results primarily in the β form. The threshold concentration above which crystalline mannitol is detected in the freeze-dried solid by X-ray diffraction is consistently about 30% (w/w) when a second, noncrystallizing solute is present, regardless of the nature of the second component. The glass transition temperature of amorphous mannitol measured from the quench-cooled melt is approximately 13°C. Accordingly, mannitol is an effective plasticizer of freeze-dried solids when the mannitol remains amorphous. Glass transition temperatures of mixtures of mannitol and the disaccharides sucrose, maltose, trehalose, and lactose are well predicted by the Gordon–Taylor equation with values of k in the range of 3 to 4.

Water sorption behavior of lyophilized protein–sugar systems and implications for solid-state interactions

This study examines the water sorption behavior of proteins co-lyophilized with sugar/polyol excipients. Gravimetric sorption analysis (GSA) was used to measure water sorption of the lyophilized mixtures and these data allowed for calculation of the water monolayer ( M 0). Lyophilized protein–mannitol mixtures behaved as predicted from the data for the pure components. Mannitol was shown to crystallize upon lyophilization. For protein co-lyophilized with sucrose or trehalose, which remain amorphous upon lyophilization, M 0 tended to be lower than that expected based on contributions of the pure protein and sugar. This negative deviation supports the view that amorphous sugars and pharmaceutical proteins interact in the solid state in such a way as to reduce the availability of water-binding sites. At high relative humidities (rh), sucrose and trehalose were susceptible to moisture-induced crystallization. When co-lyophilized protein was present, the GSA data revealed that this crystallization required a higher rh, or did not occur. For the temperature-induced (non-isothermal) sucrose crystallization, which was studied by differential scanning calorimetry, it was found that the temperature of crystallization tended to increase with an increasing amount of protein. The tendency to crystallize rose in the presence of elevated moisture, whether or not protein was present, likely due to the ability of water to plasticize the solid phase.

New method of preparing high-porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material

Compressed tablets of a water-soluble material, prepared using mannitol, did not rapidly dissolve in water since it is difficult for water to penetrate into the tablets due to their low porosity. To increase the porosity of the tablets which are prepared by direct compression using mannitol, we developed a novel method whereby camphor, a subliming material, is removed by sublimation from compressed tablets prepared using a mixture of mannitol and camphor. A high porosity was achieved due to the formation of many pores where camphor particles previously existed in the compressed mannitol tablets prior to sublimation of the camphor. These compressed tablets which have high porosity (approximately 30%) rapidly dissolved within 15 s in saliva in the mouth. We developed a direct compression method for the preparation, using mannitol and camphor, of a meclizine (antidinic agent) tablet with high porosity which dissolves rapidly in saliva.

Optimisation of the composition and production of mannitol/microcrystalline cellulose tablets

Mixtures of mannitol and microcrystalline cellulose (MCC) were investigated on a small-production scale by granulation in a high-shear mixer and compression into tablets. For both excipients only a few cases of incompatibilities with active ingredients are known. Tablets with only MCC as the filler excipient have mostly inferior strength and tablets of only mannitol disintegrate slowly. However, a combination of both excipients resulted in sufficiently rapid disintegrating tablets with acceptable strength. The composition of the tablet mixture and the process of tablet manufacturing were optimised using statistical techniques. Next to the effects of the amounts of MCC and hydroxypropylcellulose (HPC) in the composition, the effects of the amount of water and the granulation time were evaluated. For the production of tablets both the effects of moisture content in the granules and compression force were studied. Simultaneous optimisation of crushing strength, disintegration time and ejection force of the tablets was carried out to find optimal regions in the design space for these tablet properties. In conclusion, mannitol/MCC mixtures can be considered as an interesting alternative in case classical excipients cannot be selected in formulation development, due to chemical incompatibilities with active ingredients or inferior physical characteristics.

Protection of protein A-sepharose columns irradiated to sterilization doses

The effects of ionizing radiation on protein A-sepharose mini columns have been investigated. Radiolysis to a dose of 25 kGy is accompanied by a 55% loss of binding capacity to IgG. Various OH . radical scavengers have been used to render them radiation resistant at the high doses commonly used for the purpose of sterilization. Inclusion of mannitol at high concentrations (1 mol dm −3) partially protects the columns as does ascorbate (10 −2 mol dm −3), the loss of binding being only ∼15% at 25 kGy. A mixture of mannitol (1 mol dm −3) and ascorbate (10 −2 mol dm −3) however protects to ∼5% decomposition. This value is not effected by the presence of oxygen at the beginning of irradiation.

Stimulation of in vitro root and shoot growth of potato by increasing sucrose concentration in the presence of fluridone, an inhibitor of abscisic acid synthesis

Fluridone, an inhibitor of abscisic acid (ABA) biosynthesis, strongly stimulated rooting of nodal stem segments of potato (Solanum tuberosum L.) cultivar Arran Banner cultured in darkness on tuberisation medium. Inclusion of 10-6 M ABA in the culture medium prevented this rooting response, indicating that root proliferation in the presence of fluridone could be due to inhibition of ABA synthesis. The rooting response to fluridone (increased total root number and root fresh weight) was obtained only at high sucrose concentrations (0.175 and 0.234 M) and was demonstrated with two potato cultivars and two culture media; one which favoured tuberisation and one which did not. Shoot numbers were also increased, but to a lesser extent than root numbers, and total fresh weight of plant material per culture was greatly increased by inclusion of both fluridone (10-6 or 10-5 M) and 0.234 M sucrose in the culture medium. The role of sucrose was not simply osmotic because when the osmolarity of fluridone medium was increased using mixtures of mannitol and sucrose, no root proliferation occurred unless sucrose predominated in the mixture.

Jejunal Dialysis in Man Using Mannitol as the Perfusate

In four normal subjects a 50-cm segment of the jejunum was perfused through a multilumen tube with either hypertonic (1300 mOsm/kg) or isotonic mixtures of mannitol and water at rates between 18 and 70 ml/min. There was no difference in the solute clearances produced by the two solutions. Mean clearances (ml/min) were urea 23, creatinine 8, urate 4. Ninety-five mmol of sodium and 3.8 mmol of potassium were removed during a 1-h perfusion period. Clearances of glucose, calcium, phosphate and protein were negligible. Mean free water clearance was 0.5 ml/min during isotonic perfusion and 22.4 ml/min during hypertonic perfusion. These clearances of urea and creatinine are similar to those previously reported during perfusion of the whole bowel in uraemic patients with isotonic mannitol and during segmental jejunal perfusion with glucose/sodium mixtures. Over the range of flow rates studied there was a positive linear relationship between perfusate flow rates might achieve clinically useful solute clearance. However, the efficacy of the method in prolonged perfusion of uraemic patients may be different from that seen in normal subjects.

Effect of total starvation and very low calorie diets on intestinal permeability in man.

1. The effect of total starvation for 4-5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5g), [14C]mannitol (0.5 microCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 microCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g). [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P less than 0.025), 33% in group 2 obese subjects (P less than 0.05) and 41% in group 3 obese subjects P greater than 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate as markers of intestinal permeability in man

1. Factors affecting the intestinal uptake and urinary excretion of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), have been investigated in normal subjects and three patients with ileostomy. 2. The distribution volume of markers within the body, the rate of disappearance from plasma and renal clearance were assessed after an intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 3. The urinary recovery of all the intravenously administered markers was close to 100%. Distribution volumes and patterns of excretion were virtually identical. Oxidation of intravenously administered mannitol accounted for only about 1% of the dose. 4. The passage of an orally administered mixture of markers was traced through the intestine and into urine. Transit time through the gastrointestinal tract was measured by the breath hydrogen method and by radionuclide scanning. 5. The passage of markers from mouth to the large bowel was essentially complete by 3.5 h. In some subjects the marker appeared in the large bowel as early as 30-40 min but in others it took three times as long. 6. After an oral dose the urinary excretion of mannitol fell progressively from 2 to 6 h, whereas the excretion of lactulose and 51Cr-EDTA increased slightly. As a consequence the lactulose/mannitol and 51Cr-EDTA/mannitol ratios in urine collected between 0 and 2 h were more than twofold higher than in urine collected between 4 and 6 h (P less than 0.001). After 6 h, the urinary excretion

Reversal of the mannitol-sorbitol diauxie in Escherichia coli.

In Escherichia coli K-12 the proteins involved in the dissimilation of mannitol and sorbitol are specified by two separate gene clusters. The mannitol cluster appears to consist of a regulatory gene mtlC, a gene mtlA coding an enzyme II complex of the phosphoenolpyruvate phosphotransferase system, and a gene mtlD coding a mannitol-1-phosphate dehydrogenase. Three corresponding genes, sblC, sblA, and sblD, exist for the sorbitol pathway. In both pathways the hexitol captured from the medium and delivered into the cytoplasm as a phosphorylated compound is dehydrogenated to fructose-6-phosphate. The enzyme II complex for sorbitol is able to catalyze the phosphorylation also of mannitol if this substrate is present at high concentrations. Consequently mtlA(-) mutants lacking the enzyme II complex for mannitol can grow on mannitol either if the sorbitol phosphorylating system is preinduced by sorbitol or if mtlA is suppressed by a mutation of sblC to constitutivity. In wild-type cells, the induction of the enzymes in the mannitol pathway and dissimilation of the substrate are not prevented by glucose. The sorbitol system, however, is sensitive to glucose and to mannitol as well. In the suppressed strains (mtlA(-), sblC(c)) in which mannitol is utilized through the sorbitol enzyme, glucose becomes effective in restraining the consumption of mannitol, causing a definite diauxie. Moreover, in a mixture of mannitol and sorbitol, the latter is utilized preferentially. This reversal of normal diauxic pattern is consequent to the fact that the enzyme II complex for sorbitol has relatively poor affinity for mannitol.

EXTRACELLULAR GLYCOLIPIDS OF RHODOTORULA SPECIES: THE ISOLATION AND SYNTHESIS OF 3-D-HYDROXYPALMITIC AND 3-D-HYDROXYSTEARIC ACIDS

Several species of the red yeast Rhodotorula produce extracellular glycolipids which consist of a mixture of mannitol and pentitol esters of 3-D-hydroxypalmitic and 3-D-hydroxystearic acids. One molecule of the long chain acid is attached to each polyol molecule and most of the remaining hydroxyl groups including the one on the fatty acid are acetylated.

Studies in the Biochemistry of Micro-organisms. Part X.—The estimation of Mannitol in fermentation solutions

This paper deals with the problem of estimating mannitol in the presence of glucose and of products arising during the fermentation of this sugar. Work was started by preparing synthetic mixtures of pure mannitol and pure glucose, and, a satisfactory method of estimating each of these in presence of the other having been found, the effect of the presence of other fermentation products, e.g. , glycerol, on the accuracy of the method was tested. A successful solution of the problem was found in the use of the polarimeter. Details of the polarimetric work carried out on pure mannitol and glucose are given on pp. 173-185. Chemical methods which were also tried on these substances were :— (1) Estimation of mannitol as the tribenzoyl acetal, or as the ^-nitrobenzoyl derivative (see p. 185). (2) Estimation of mannitol by acetylation (see pp. 185-187). The use of the polarimetric and acetylation methods in conjunction with each other on synthetic mixtures of mannitol and glucose was next tried and is described on pp. 187-198, and then the application of these methods to actual fermentation solutions was investigated, the results being given on pp. 200-207. Finally, a quicker but somewhat less accurate method for the estimation of mannitol in fermentation solutions, which obviates the time-consuming step of removing glucose by fermentation, was devised for routine use and is discussed on pp. 198-200.