Lactose In Water Research Articles

β-galactosidase orodispersible dosage forms for the treatment of lactose intolerance

Lactose intolerance is associated with the insurgence of mild to severe gastrointestinal symptoms. The administration of β-galactosidase (β-gal) tablets or capsules, which are unsuitable for the dysphagic population, is the main symptomatic treatment. This work aimed to demonstrate the feasibility of β-gal orodispersible films (ODF) prepared by solvent casting technique. Since the preparation involves thermal and mechanical stresses, which can compromise the enzyme stability, in vitro performances of ODF were compared to those of oral lyophilizates (OL).ODF were made of maltodextrin DE6, glycerol and Capryol®90. OL made of different grades of maltodextrins, and sorbitol or trehalose were prepared in aluminium blisters. ODF and OL were assayed for disintegration time and β-gal activity. The hydrolysis rate of lactose was determined using: a) a placebo capsule (500 mg lactose) disintegrated in a glass of water; b) 150 mL milk in biorelevant media. ODF (6 cm2) and OL (made of maltodextrin DE19 and trehalose). ODF and OL loaded with about 4000 UI of β-gal were stable over 3 months of storage at 25 °C/60% RH. Both of them allowed the hydrolysis of lactose in water within 15 min. The complex composition of milk affected the hydrolysis rate (K) of lactose: the reaction was faster in fasted-state media (K ≈ −0.07 min−1) than in those simulating the fed state of subjects with physiologically appreciable residual gastric fluid in the stomach (grade 1 antrum: 20 mL, K ≈ −0.005 min−1; grade 2 antrum: 180 mL, K ≈ −0.01 min−1). No significant differences were noticed between ODF and OL. Overall, ODF can be proposed to hydrolyse lactose contained in immediate release dosage forms, improving the patient's adherence to therapy. Moreover, the dependence of the lactose degradation kinetic not only on the fed or fasted conditions, but also on the antrum phenotype may allow the development of ODF in a more patient-centric perspective.

Analysing the molecular interactions of ternary (lactose + water + tributylmethylammonium chloride) solutions at different temperatures via physicochemical methods

The interactions of lactose with tributylmethylammonium chloride (Bu3MeNCl) as the function of temperature have been studied by amalgamation of volumetric, acoustic and viscometric methods. Density, ultrasonic speed, and viscosity for varying concentrations of lactose in water and in (0.020, 0.039, 0.059, 0.079) mol.kg−1 aqueous solutions of Bu3MeNCl have been determined at five distinct temperatures (T = 293.15–313.15) K. These experimental values have been used to calculate apparent molar volume, Vϕ, limiting apparent molar volume, V0ϕ, apparent molar isentropic compression, Kϕ,s, limiting apparent molar isentropic compression, K0ϕ,s, viscosity B-coefficient, their transfer values, pair and triplet interaction coefficients, and hydration number nH. The Gibbs free energy of activation for solvent (Δµ01#) and Gibbs free energy of activation for lactose (Δµ02#) in water and in aqueous solutions of Bu3MeNCl have also been assessed and the obtained results support the outcome of volumetric, acoustic and viscometric parameters. These parameters provide better understanding of molecular interactions like solute-solute, solute-solvent interactions present in the systems. Further, it helps in determining structural and functional properties of studied systems and acquired results revealed that the solutions are characterized predominantly by solute-solvent interactions. Also, the values of second derivative of limiting apparent molar volume with respect to temperature indicated that the lactose monohydrate behaves as a structure maker in aqueous tributylmethylammonium chloride solutions.

Spray drying lactose from organic solvent suspensions for aerosol delivery to the lungs.

Lactose is widely used as an approved excipient for dry powder inhaler (DPI) products. Spray drying technique is a rapid method for converting a liquid feed into inhalable dried particles. However, spray-dried (SD) lactose powders produced from solutions are mostly amorphous and particularly unstable when exposed to moisture. In the present study, we explored the use of spray drying suspensions containing crystalline lactose particles in an organic solvent, and investigated the physicochemical properties of the resulting powders. The solution formulation was spray dried as a control. Two conditioned crystalline lactose samples were used for suspension formulations: Lactohale (LH) 300 lactose and jet-milled (JM) lactose micronized from LH300. The suspension formulations each contained 12mg/ml suspended crystalline lactose particles (either LH300 or JM lactose) in isopropyl alcohol. The solution formulation contained 60mg/ml lactose in water. The SD powders were stored under 25°C/60% RH and 40°C/75% RH for 3months. The particulate properties and in vitro dispersion performance were examined at various time points. The SD lactose obtained from solution recrystallized and was no longer dispersible after 1-day storage at both storage conditions. The suspension SD JM lactose powder showed deterioration in the particulate properties and dispersibility over time, but more gradually. In contrast, the SD LH300 powder was stable, with its particulate properties and dispersion performance (FPF: ~12%) remaining the same after 3-months storage at 25°C/60% RH. The SD LH300 stored at 40°C/75% RH showed no change in particulate properties, but the FPF decreased over 3months. Overall, SD lactose powders obtained from suspension demonstrated superior stability performance compared to SD lactose obtained from solution.

Effect of temperature and concentration alterations on the volumetric, acoustic and hydration studies of l-threonine in aqueous lactose solutions

The density and speed of sound in the solution of l-threonine in the concentration range (0.025 to 0.2) mol kg−1 in water and various lactose solutions (0 to 6 mass% of lactose in water) have been carried out at temperatures range of (293.15 to 313.15) K. The experimental data is used to obtain the apparent molar volume (Vϕ), limiting apparent molar volume (V0ϕ), limiting apparent molar transfer volume (V0ϕ,tr), as well as apparent molar compressibility (Ks,ϕ), limiting apparent molar compressibility (K0s,ϕ), limiting apparent molar transfer compressibility (K0s,ϕ,tr), pair and triplet interaction coefficients for volume and compressibility (VAB, VABB and KAB, KABB), limiting partial molar expansibility (ϕ0E), coefficient of thermal expansion (α) and hydration number (nH) of amino acid. The results have been interpreted in terms of solute-solute and solute-solvent interactions; and hydration characteristics of amino acid molecules in aqueous lactose solutions.

Molecular Interactions in L-threonine Aqueous-Lactose Solutions at (293.15–313.15) K on Viscometric Data

Viscosity measurements of L-threonine in the range (0.025–0.2) mol kg–1 in various aqueous-lactose solutions (0–6 wt % of lactose in water) have been carried out at temperatures (293.15–313.15) K. Jones–Dole coefficients, viscosity B-coefficients of transfer, Btr, variation of B with temperature, dB/dT and solvation behavior, B/ $$V_{\phi }^{^\circ }$$ of L-threonine have been obtained. Further, the free energy of activation of viscous flow per mole of solvent, as well as per mole of solute, along with activation enthalpy, and activation entropy has also been evaluated. The results have been interpreted in terms of various molecular interactions prevalent in these systems and moreover, it has been seen that the L-threonine acts as structure maker in all studied solutions.

Monitoramento da cristalização da lactose em soro concentrado

The kinetics of lactose crystal growth in concentrated whey were studied in two stages. The first took place in a bench-top crystallizer and the second in an industrial crystallizer using concentrated whey obtained by vacuum evaporation, consisting of 3 treatments: crystallization by primary nucleation, by secondary nucleation with the addition of 0.05% and with the addition of 0.1% microcrystalline lactose. The average size of the crystals remained between 60.7 mm and 63.8 mm. The percentage of crystallization was greater in the secondary nucleation process than in the primary nucleation, where crystallization stabilized first. Mathematical equations which independently related crystallization times of the concentrated whey to the concentrations of soluble solids, crystallization percentage and mass of lactose in water were established, that can be used in the industrial setting to process whey. The kinetics of lactose crystal growth was not well described by models of first or second order reactions.

Stability of sugar solutions: a novel study of the epimerization kinetics of lactose in water.

This article reports on the stereochemical aspects of the chemical stability of lactose solutions stored between 25 and 60 °C. The lactose used for the preparation of the aqueous solutions was α-lactose monohydrate with an anomer purity of 96% α and 4% β based on the supplied certificate of analysis (using a GC analytical protocol), which was further confirmed here by nuclear magnetic resonance (NMR) analysis. Aliquots of lactose solutions were collected at different time points after the solutions were prepared and freeze-dried to remove water and halt epimerization for subsequent analysis by NMR. Epimerization was also monitored by polarimetry and infrared spectroscopy using a specially adapted Fourier transform infrared attenuated total reflectance (FTIR-ATR) method. Hydrolysis was analyzed by ion chromatography. The three different analytical approaches unambiguously showed that the epimerization of lactose in aqueous solution follows first order reversible kinetics between 25 to 60 °C. The overall rate constant was 4.4 × 10(-4) s(-1) ± 0.9 (± standard deviation (SD)) at 25 °C. The forward rate constant was 1.6 times greater than the reverse rate constant, leading to an equilibrium constant of 1.6 ± 0.1 (±SD) at 25 °C. The rate of epimerization for lactose increased with temperature and an Arrhenius plot yielded an activation energy of +52.3 kJ/mol supporting the hypothesis that the mechanism of lactose epimerization involves the formation of extremely short-lived intermediate structures. The main mechanism affecting lactose stability is epimerization, as no permanent hydrolysis or chemical degradation was observed. When preparing aqueous solutions of lactose, immediate storage in an ice bath at 0 °C will allow approximately 3 min (180 s) of analysis time before the anomeric ratio alters significantly (greater than 1%) from the solid state composition of the starting material. In contrast a controlled anomeric composition (~38% α and ~62% β) will be achieved if an aqueous solution is left to equilibrate for over 4 h at 25 °C, while increasing the temperature up to 60 °C rapidly reduces the required equilibration time.

Solubility and physical properties of sugars in pressurized water

In this study, the solubility, density, and refractive index of glucose and lactose in water as a function of temperature were measured. For solubility of sugars in pressurized water, experimental data were obtained at pressures of (15 to 120) bar and temperatures of (373 to 433)K using a dynamic flow high pressure system. Density data for aqueous sugar solutions were obtained at pressures of (1 to 300)bar and temperatures of (298 to 343)K. The refractive index of aqueous sugar solutions was obtained at 293K and atmospheric pressure. Activity coefficient models, Van Laar and the Conductor-like Screening Model-Segment Activity Coefficient (COSMO-SAC), were used to fit and predict the experimental solubility data, respectively. The results obtained showed that the solubility of both sugars in pressurized water increase with an increase in temperature. However, with the increase of pressure from 15 bar to 120 bar, the solubility of both sugars in pressurized water decreased. The Van Laar model fit the experimental aqueous solubility data with deviations lower than 13 and 53% for glucose and lactose, respectively. The COSMO-SAC model predicted qualitatively the aqueous solubility of these sugars.

Solubility, Solubility Modeling, and Precipitation of Naproxen from Subcritical Water Solutions

In this paper, the solubility of naproxen in subcritical water (SBCW) between 130 and 170 °C is measured. The solubility of naproxen in SBCW was correlated to temperature using a Modified Universal Functional Activity Coefficient (M-UNIFAC) model. Errors in the model were minimized by optimizing the water−carboxylic acid interaction parameter, as other side groups were already optimized. The micronization of naproxen via processes that used the tunable solvent power of SBCW was conducted. Two precipitation techniques were developed. In the first technique, the temperature of a SBCW solution containing naproxen was rapidly quenched by injection into cold water solutions. The quenching media were either pure water or 1% w/v solution of lactose in water. Variations in SBCW−naproxen solution injection temperature and supersaturation ratios in pure water were examined. Product morphology was robust toward changes in operating conditions and consisted of flaky crystals with a particle size distribution ranging ...

A novel glycosyl donor for chemo-enzymatic oligosaccharide synthesis: 4,6-dimethoxy-1,3,5-triazin-2-yl glycoside

A novel activated glycosidic compound, 4,6-dimethoxy-1,3,5-triazin-2-yl beta-lactoside (DMT-beta-Lac), which can be prepared directly from lactose in water without using any protecting groups, was found to be an efficient glycosyl donor for enzymatic glycosylation catalyzed by an endo-1,4-beta-glucanase.

Reaction pathways of the formation of molecular products upon dissolution of γ-irradiated lactose crystals

Molecular products formed upon the dissolution of γ-irradiated crystalline lactose in water were identified using UV spectroscopy, HPLC, and chemical analysis. The effects of the storage time of irradiated lactose crystals, the pH of the solvent, and the presence of oxygen in the solvent on the composition of the final solutions of this carbohydrate were studied. It was found that a portion of molecular products resulted from post-radiation radical reactions in the crystals, whereas the other portion was formed in the course of dissolution of the solid samples.

Fructose Malabsorption and Lactose Maldigestion in Patients with Irritable Bowel Syndrome and Other GI Conditions

Purpose: Carbohydrates may play a role in symptoms experienced by patients with irritable bowel syndrome (IBS) and those with other functional or undiagnosed abdominal conditions. The purpose of this study was to determine the prevalence of fructose malabsorption (FM) and lactose maldigestion (LM) in a cohort of patients who did and did not meet Rome I and II criteria for IBS. Methods: The study group consisted of patients who were evauated for IBS, diarrhea, abdominal discomfort, bloating or other symptoms attributable to the hollow viscus. A questionnaire was completed noting demographics, Rome I and II IBS symptom criteria and exclusions. Study subjects had breath collections before and after lactose challenge with 50g powdered lactose in water and on a separate day 1 week apart challenge with fructose 25g. Breath samples were analyzed for hydrogen, methane and CO2 (for correction) using a Quintron MicroLyer model SC. FM and LM were defined by a greater than 20ppm gas rise above fasting baseline. Results: Of the 66 subjects (72% of the study cohort) who met IBS criteria, there were 54 females and 12 males. The mean age of the IBS group was 47 years ± 14. Nine (14%) had FM and 26 (39%) had LM. Of those who did not meet IBS criteria, there were 19 females and 7 males. The mean age was 56 ± 12. Three (11%) had FM and nine (34%) had LM. No symptom or demographic predicted carbohydrate challenge results. Conclusions: The prevalence of FM and LM are such that carbohydrate testing is advised for those with IBS and other functional and undiagnosed gastrointestinal conditions. Further experience and investigation will be needed to elucidate the clinical importance of FM and LM in these disorders.

How Much Lactose is Low Lactose?

Objective To test the hypothesis that complete elimination of lactose is not necessary to ensure tolerance by lactose maldigesters. Design Double-blind, randomized protocol in which challenge doses of 0, 2, 6, 12, and 20 g lactose in water were fed to subjects after a 12-hour fast. Subjects 13 healthy, free-living adults who were lactose maldigesters. Main outcome measures Breath hydrogen production (a measure of maldigestion) and symptom response to each challenge dose. Statistical analysis Analysis of variance was done to determine overall differences in mean hydrogen gas production (peak and sum of hours 1 through 8). Friedman's test was used to determine overall differences in the mean ranks for each symptom. Fisher's least significant difference test was used for multiple comparisons for hydrogen and symptom and data. Results Hydrogen production after consumption of the 0- and 2-g lactose doses was not significantly different. Hydrogen production increased with the 6-g dose. Intensity of abdominal pain increased when the dose of lactose was 12 g. Episodes of flatulence did not increase until the dose reached 20 g. No significant differences in the occurrence of diarrhea were observed after the five treatments. Conclusions No significant increase in breath hydrogen production or intolerance symptoms occurred after consumption of a 2-g dose of lactose. Up to 6 g was tolerated, even though maldigestion could be measured at the 6-g dose. Thus, lactose maldigesters may be able to tolerate foods containing 6 g lactose or less per serving, such as hard cheeses and small servings (120 mL or less) of milk. J Am Diet Assoc. 1996; 96:243-246.

Bench-Scale Reactor Tests of Low Temperature, Catalytic Gasification of Wet Industrial Wastes

Bench-scale reactor tests are under way at Pacific Northwest Laboratory to develop a low temperature, catalytic gasification system. The system, licensed under the trade name Thermochemical Environmental Energy System (TEES®), is designed for to a wide variety of feedstocks ranging from dilute organics in water to waste sludges from food processing. The current research program is focused on the use of a continuous feed, tubular reactor. The catalyst is nickel metal on an inert support. Typical results show that feedstocks such as solutions of 2 percent para-cresol or 5 percent and 10 percent lactose in water or cheese whey can be processed to >99 percent reduction of chemical oxygen demand (COD) at a rate of up to 2 L/hr. The estimated residence time is less than 5 min at 360°C and 3000 psig, not including 1 to 2 min required in the preheating zone of the reactor. The liquid hourly space velocity has been varied from 1.8 to 2.9 L feedstock/L catalyst/hr depending on the feedstock. The product fuel gas contains 40 percent to 55 percent methane, 35 percent to 50 percent carbon dioxide, and 5 percent to 10 percent hydrogen with as much as 2 percent ethane, but less than 0.1 percent ethylene or carbon monoxide, and small amounts of higher hydrocarbons. The byproduct water stream carries residual organics amounting to less than 500 mg/L COD.

Effect of Dietary Lactose on Cecal pH, Bacteriostatic Volatile Fatty Acids, and Salmonella typhimurium Colonization of Broiler Chicks

One-day-old broiler chicks were inoculated with volatile fatty acid producing cecal flora from adult chickens. The chicks were divided into four groups and provided 1) no lactose, 2) 2.5% lactose in water, 3) 5% lactose in feed, or 4) 10% lactose in feed, until 10 days of age. All groups were challenged at 3 days of age with 10(6) or 10(8) S. typhimurium. At 10 days, the number of Salmonella in the ceca of the chicks challenged with 10(6) Salmonella was significantly decreased (P less than 0.01) in the groups provided lactose as compared with the controls. A significant decrease (P less than 0.01) in Salmonella numbers occurred in the chicks challenged with 10(8) Salmonella and provided 10% lactose. Providing 2.5% lactose or 5% lactose failed to inhibit Salmonella growth in chicks challenged with 10(8) Salmonella. The pH of the ceca of the groups provided lactose decreased significantly (P less than 0.05) and was accompanied by significant increases (P less than 0.01) in the concentrations of bacteriostatic acetic and propionic acids. Results showed that providing dietary lactose to broiler chicks and inoculation with normal cecal flora decreased cecal pH, increased the concentrations of bacteriostatic volatile fatty acids, and inhibited Salmonella colonization.

The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance

1) Most humans, like other mammals, gradually lose the intestinal enzyme lactase after infancy and with it the ability to digest lactose, the principle sugar in milk. At some point in prehistory, a genetic mutation occurred and lactase activity persisted in a majority of the adult population of Northern and Central Europe. 2) Persistence of intestinal lactase, the uncommon trait worldwide, is inherited as a highly penetrant autosomal-dominant characteristic. Both types of progeny are almost equally common when one parent is a lactose maldigester and the other a lactose digester. 3) The incidence of lactose maldigestion is usually determined in adults by the administration in the fasting state of a 50-g dose of lactose in water, the equivalent of that in 1 L of milk. Measurement is made of either the subsequent rise in blood glucose or the appearance of additional hydrogen in the breath. It is also sometimes identified by measuring lactase activity directly in a biopsy sample from the jejunum. For children the test dose is reduced according to weight. Depending on the severity of the lactase deficiency and other factors, the test dose may result in abdominal distention, pain, and diarrhea. 4) The frequency of lactose maldigestion varies widely among populations but is high in nearly all but those of European origin. In North American adults lactose maldigestion is found in approximately 79% of Native Americans, 75% of blacks, 51% of Hispanics, and 21% of Caucasians. In Africa, Asia, and Latin America prevalence rates range from 15-100% depending on the population studied. 5) Whenever the lactose ingested exceeds the capacity of the intestinal lactase to split it into the simple sugars glucose and galactose, which are absorbed directly, it passes undigested to the large intestine. There it is fermented by the colonic flora, with short-chain fatty acids and hydrogen gas as major products. The gas produced can cause abdominal distention and pain and diarrhea may also result from the fermentation products. 6) Among individuals with incomplete lactose digestion, there is considerable variation in awareness of lactose intolerance and in the quantity of lactose that can be ingested without symptoms. A positive standard lactose test is not a reliable predictor of the ability of an individual to consume moderate amounts of milk and milk products without symptoms. In usual situations the quantity of lactose ingested at any one time is much less than in the lactose-tolerance test.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of fiber on breath hydrogen response and symptoms after oral lactose in lactose malabsorbers

The effect of ingesting cellulose, pectin, and psyllium with orally administered lactose in water or milk was tested in six lactose malabsorbers. Breath hydrogen tests were used to evaluate lactose malabsorption and mouth-to-cecum transit times. Addition of psyllium significantly reduced the breath hydrogen response, and symptoms in each subject; whereas, less diminution of expired hydrogen was seen after cellulose or pectin was added. The effect of each fiber on gastric emptying rates of an equal volume liquid meal was evaluated in three volunteers. Pectin had no effect, while the cellulose and psyllium modestly delayed emptying at approximately 30 min.

Gastric emptying of lactose and milk in subjects with lactose malabsorption.

Six lactose absorbers (LA) and 5 lactose malabsorbers (LM) had tests of gastric emptying with 750-ml meals of glucose in water, lactose in water, plain milk, and chocolate milk. The glucose and lactose meals emptied in a similar fashion in LA and LM subjects with a significant decrease in gastric emptying as the osmolarity of the meals was doubled. If the data are normalized by dividing lactose emptying by the emptying of glucose meals of twice the osmolality in each individual, the lactose malabsorbers empty significantly more lactose. Both LA and LM subjects emptied comparable amounts of milk meals having similar osmolarity. Chocolate milk, which had a higher osmolality than plain milk, emptied more slowly than plain milk in both groups, and this difference was significant in the LM group.

Utilization of a low-lactose milk

This study was undertaken to determine if a milk containing prehydrolyzed lactose, yet affording full nutritional benefits, could be ingested by a milk intolerant (MI) population without the symptoms of lactose intolerance. MI was defined by the failure of serum glucose to rise greater than 20 mg/100 ml after ingestion of 50 gm of lactose as well as by subjective and objective symptoms and signs after consumption of both 12.5 gm of lactose in water and 250 ml of skim milk. Lactose tolerance (LT) was evidenced by both lack of symptoms and a concomitant rise in serum glucose of greater than 20 mg/100 ml after ingestion of 50 gm lactose in water. A series of four, two hr tolerance tests were given to 12 MI patients and 12 LT controls. The following solutions were employed: 12.5 gm lactose, 250 ml skim milk. 250 ml low-lactose skim milk, and 6 gm glucose plus 6 gm galactose. In the MI group, significant differences were apparent between the tolerance test utilizing skim milk and that using low-lactose skim milk; no such differences were observed in the LT group. These observations indicate that in the MI population the lactose in skim milk was poorly absorbed or tolerated, but after hydrolysis the low-lactose skim milk was well tolerated. A MI individual then, appears able to absorb the monosaccharides of the prehydrolyzed milk and can, furthermore, tolerate the low-lactose skim milk without suffering from symptoms normally associated with lactose intolerance.

Symptom response to lactose-reduced milk in lactose-intolerant adults

The possible usefulness of low-lactose milk for those lactose-intolerant subjects who develop symptoms from milk consumption was investigated. In the first part of the study, 16 intolerant subjects (blood glucose rise less than 25 mg/100 ml) received low-lactose skim milk containing 15 g lactose (2.5 cups) and 7.5 g lactose (2.5 cups), regular skim milk containing 30 g lactose (2.5 cups), and all three milks plus a small breakfast. The low lactose milks produced significantly fewer symptoms. The food given with the milk had no significant effect on symptomatic response. The second group of 17 subjects received 25 g lactose in water (250 ml), skim milk (500 ml) and whole milk (500 ml); 10 g lactose in lactose-reduced skim (500 ml) and whole milk (500 ml) and whole milk (500 ml); and a placebo (250 ml). There was a significant positive relationship between amount of lactose consumed and symptom response. The form in which the lactose was administered (e.g., whole versus skim milk) was not significantly related to symptoms. It is concluded that in a symptomatic subjects a significantly greater quantity of low-lactose milk than regular milks can be consumed.