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Use of near-infrared for quantitative measurement of viscosity and concentration of active ingredient in pharmaceutical gel.

Near infrared (NIR) spectroscopy is gaining worldwide interest as an analytical tool for quality control of raw materials, intermediate products, and final dosage forms. This technique can be used without sample preparation, therefore, avoiding the need for reagents and solvents. Quantitative NIR analyses involve calibration by sophisticated mathematical techniques that have been used extensively since the advent of microcomputing and chemometrics. The main objective of this investigation was to use transmission near-Infrared spectroscopy to measure the potency of an active ingredient in a topical gel preparation. A second objective was to evaluate the effect of gel viscosity on the NIR reflectance spectra. Four gel formulations with different ibuprofen concentrations were used for quantitative determination of the active ingredient, and five gel formulations with different viscosity values were used for the evaluation of the effect of viscosity change on the near-infrared reflectance spectra. The laboratory ibuprofen quantitative determination was compared to near-infrared transmission data using linear, quadratic, cubic and partial least square techniques to determine the relationship between ultraviolet (UV) determination and near-infrared spectra. For viscosity, the laboratory data were compared to near-infrared diffuse reflectance data using the same techniques used to determine the relationship between Brookfield viscometer determination and near-infrared spectra. The results demonstrated that an increase in ibuprofen concentration and viscosity produced an increase in near-infrared absorbance. Series of model equations were developed from the calibration of laboratory vs. the near-infrared data for each formulation. The near-infrared spectroscopy method is an alternative method that does not require sample pretreatment for quantitative measurement of active ingredient and viscosity of pharmaceutical gel.

Anti-Inflammatory Agents, Non-Steroidal↗

Release of furosemide from multiple-unit and single-unit preparations containing different viscosity grades of sodium alginate.

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while high viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero-order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.

Alginates↗

Some perspectives on the viscosity of actin filaments.

Measurements of the dynamic viscosity of various actin filament preparations under conditions of low and controlled shear: (a) confirm the shear rate dependence of F-actin viscosities and show that this dependence obeys the power law relationship observed for entangled synthetic polymers; (b) permit estimation of the extent to which shear artifact amplifies changes in the apparent viscosity of F-actin measured in a falling ball viscometer; (c) show that gel-filtration chromatography of actin and the addition of cytochalasin B to F-actin bring about small (20-40%) changes in the viscosity of the F-actin solutions. These variations are consistent with alterations in the actin-binding protein concentrations required for incipient gelation, a parameter inversely related to average filament length. Therefore: (a) changes in the viscosity of F-actin can be magnified by use of the falling ball viscometer, and may exaggerate their biological importance; (b) chromatography of actin may not be required to obtain meaningful information about the rheology of actin filaments; (c) changes in actin filament length can satisfactorily explain alterations in F-actin viscosity exerted by cytochalasin B and by chromatography, obviating the need to postulate specific interfilament interactions.

Actins↗

The effect of sweeteners on perceived viscosity.

Two different sweeteners, sucrose and aspartame, were matched in perceived sweetness intensity. These solutions were thickened with carboxymethylcellulose to six different viscosity levels. Sucrose and aspartame appeared to decrease perceived viscosity of the solutions at a specific sweetener concentration, at all viscosity levels. However, in a second similar experiment with three viscosity levels and seven sucrose concentrations no effect of sucrose concentration on perceived viscosity was found. Reasons for these conflicting results are discussed. No definite conclusions about the effect of sweeteners on perceived viscosity can as yet be drawn.

Adult↗

The differences in intestinal viscosity produced by barley and beta-glucanase alter digesta enzyme activities and ileal nutrient digestibilities more in broiler chicks than in cocks.

The objectives of this study were to determine whether intestinal viscosity caused by mixed linked barley beta-glucan depresses ileal nutrient digestibility and digestive enzyme activities and to determine the interaction of intestinal viscosity, digestive enzyme activities and ileal nutrient digestibility in different ages of poultry. In Experiments 1 and 2, 1-d-old broiler chicks and 1-y-old cocks, respectively, were fed diets with 60% corn, low and high viscosity barley with or without beta-glucanase, for 3 wk. A 3 x 2 factorial design was used. Comparisons were made only within the same age group. In Experiment 3, 1-d-old broiler chicks were fed high viscosity barley with and without beta-glucanase to measure fecal nutrient and ileal and fecal amino acid digestibility. Broiler chicks fed barley ate less and gained less weight than those fed corn; added beta-glucanase resulted in increases in both food consumption and weight gain for the barley-fed chicks (P < 0.05). Relative pancreas weight was higher (P < 0.05) in chicks fed barley than in those fed corn, and lower with beta-glucanase (P < 0.05). Digesta from barley-fed birds had the highest viscosities, which were decreased (P < 0.05) by beta-glucanase. Amylase and lipase were lower in broiler chicks fed high viscosity barley compared with corn (P < 0.05), and beta-glucanase increased both activities and that of trypsin as well (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Dietary pectin with high viscosity lowers plasma and liver cholesterol concentration and plasma cholesteryl ester transfer protein activity in hamsters.

We fed semipurified diets containing pectin with either a high or low in vitro viscosity at a level of 3 g/100 g air-dried diet to hamsters for 8 wk. A control group was fed cellulose and a positive control group was fed psyllium. The pectins used were a calcium-sensitive pectin (CS-pectin) that has a high viscosity and a noncalcium-sensitive pectin (NCS-pectin) that has a low viscosity. In the presence of calcium, CS-pectin has a more than 80-fold higher viscosity than NCS-pectin which offered the opportunity to investigate the possible role of viscosity in the hypolipidemic properties of pectin. The hamsters fed CS-pectin or psyllium had considerably lower plasma cholesterol concentrations (3.69 +/- 0.44 and 4.21 +/- 0.45 mmol/L, respectively, mean +/- SD, n = 14) than those fed NCS-pectin (5.03 +/- 1.15 mmol/L) or cellulose (5.72 +/- 1. 04 mmol/L). Differences in total plasma cholesterol were reflected in both high density lipoprotein and very low density lipoprotein cholesterol. There was no effect of fiber on low density lipoprotein cholesterol levels. Liver cholesterol concentrations paralleled the plasma cholesterol levels and were 9.91 +/- 2.48 micromol/g of liver for the CS-pectin group, 15.03 +/- 5.75 for the psyllium group, 17. 69 +/- 10.66 for the NCS-pectin group, and 25.57 +/- 9.23 for the cellulose group. Fecal bile acid and neutral steroid excretion tended to be higher in the hamsters fed CS-pectin than in their counterparts fed NCS-pectin. The hamsters fed psyllium had significantly greater fecal excretions of bile acids than the hamsters fed cellulose, CS-pectin or NCS-pectin, whereas the excretion of fecal neutral sterols tended to be lower. Plasma cholesteryl ester transfer protein activity was significantly lower in the hamsters fed CS-pectin than in those fed NCS-pectin. The results of this study suggest that the viscosity of pectins may determine their cholesterolemic effect.

Animals↗

Large particles increase viscosity and yield stress of pig cecal contents without changing basic viscoelastic properties.

The viscosity of gut contents should influence digestion and absorption. Earlier investigators measured the viscosity of intestinal contents after the removal of solid particles. However, we previously found that removal of solid particles from pig cecal contents dramatically lowered the viscosity of the contents. Accordingly, we examined the contribution of large solid particles to viscoelastic parameters of gut contents in the present study. We removed large particles from pig cecal contents by filtration through surgical gauze. Then, we reconstructed the cecal contents by returning all, one half or none of the original amount of the large particles to the filtrate. We measured the viscosity, shear stress and shear rate of these reconstructed cecal contents using a tube-flow viscometer. The coefficient of viscosity was larger when the large-particle content was higher (P < 0.01). Cecal contents behaved as a non-Newtonian fluid and showed an apparent Bingham plastic nature irrespective of large-particle content. We calculated the yield stress of these fluids assuming that the fluids behave as Bingham plastic. The yield stress of the cecal contents was greater (P < 0.05) when the large-particle content was higher. The above results indicated that large particles elevated the viscosity and yield stress of gut contents without changing their basic viscoelastic character. Integrating the present and our previous results, we conclude that it is likely that finer particles such as bacteria should provide non-Newtonian and apparent Bingham plastic characteristics to pig cecal contents.

Animals↗

Fibrinogen, viscosity and the 10-year incidence of ischaemic heart disease.

AIMS: To use the ten year follow-up of the Caerphilly and Speedwell studies to assess the contributions of fibrinogen and viscosity to the prediction of risk of ischaemic heart disease. METHODS AND RESULTS: Caerphilly and Speedwell are prospective studies based on representative samples of middle-aged males. Ischaemic heart disease morbidity and mortality were defined using hospital notes, repeat electro-cardiographs and death certificates. There were 603 incident events among the 4860 men. Age-adjusted relative odds of ischaemic heart disease increased to 3.3 and 3.4 in the 20% of men with the highest levels of fibrinogen and viscosity, respectively. After standardizing for the major cardiovascular risk factors, these relative odds were 2.2 (95% confidence interval 1.6 to 3.1) for fibrinogen and 2.3 (95% confidence interval 1.7 to 3.2) for viscosity. When fibrinogen and viscosity were entered jointly, both remained significant (P < 0.01) predictors. Incidence of ischaemic heart disease increased with increasing fibrinogen at every level of viscosity, and vice versa. Interactions with lipids were also examined. There was no support for the suggestion that risk is independent of cholesterol level when fibrinogen is low. CONCLUSIONS: Fibrinogen and viscosity are powerful, long term and independent predictors of the risk of ischaemic heart disease.

Age Distribution↗

Effect of storage time and dietary enzyme on the metabolizable energy and digesta viscosity of barley-based diets for poultry.

The effect of barley storage time and dietary enzyme addition on the energy value of barley-based broiler diets was studied in two experiments. A two-rowed winter barley (Beka cultivar) was stored at room temperature for 0, 3, 6, 16, and 32 wk after harvesting. At these dates, diets were formulated using 50% barley with and without the addition of a commercial beta-glucanase-based enzyme product. In Experiment 1, 320 Arbor Acres chickens (eight replicates of three 10-d-old birds and eight replicates of one 30-d-old bird, per treatment) were fed the experimental diets to determine the AMEn following a 2 x 2 x 5 (age by enzyme by barley storage time) factorial design. At the end of the metabolism trial, viscosity of the intestinal contents was determined in 30-d-old broilers. Total beta-glucan, nonstarch polysaccharides (NSP), in vitro viscosity, and endogenous enzyme activity of barley grain decreased with increasing storage time. Dietary AMEn increased with barley storage time (from 2,755 to 2,939 kcal/kg DM, P < 0.001, for 0 and 32 wk of storage, respectively), with enzyme addition (2,861 vs 2,919 kcal/kg DM, P < 0.003), and with the age of animals (2,826 and 2,958 kcal/kg DM for 10- and 30-d-old chickens, respectively, P < 0.001). Interactions of enzyme and age by barley storage time (P < 0.02 and P < 0.001, respectively) were also detected. These data indicate that the minimum time of barley storage before its inclusion in broiler feed depends on the animals' age (more than 6 wk for 10-d-old chickens and 3 wk for 30-d-old chickens), and that the use of enzymes allowed a reduction in the time of barley storage. Digesta viscosity decreased with barley storage time (P < 0.001), and with enzyme addition (P < 0.001), an interaction of storage time by enzyme addition was shown (P < 0.007). Digesta viscosity was also negatively related to the dietary AMEn content (r = -0.68, P < 0.01). In vitro barley viscosity explained 53 and 90% of the variation in gut viscosity produced by unsupplemented and enzyme supplemented diets, respectively. In Experiment 2, the same diets as Experiment 1 and the barley grain were intubated into 120 adult roosters (Hy-Line) to determine TMEn. Dietary and barley TMEn values were not affected by barley storage time or enzyme addition (3,237 and 3,037 kcal TMEn/kg DM for diets and barley, respectively).

Animal Feed↗

Plasma viscosity and its biochemical predictors: associations with lifestyle factors in healthy middle-aged men.

The association of lifestyle factors and biochemical variables with plasma viscosity was examined in a sample of middle-aged males of high social status. Analyses were performed on a subsample of men that had relevant rheological and biochemical variables determined during a preventive medical assessment conducted between 1992 and 1996. Among 622 subjects (64 smokers), measures of physical activity or predicted VO2max and adiposity (sum of subcutaneous skinfolds) were the lifestyle factors significantly associated with plasma viscosity (both P < 0.001). Among the biochemical variables, serum total protein and plasma fibrinogen concentrations accounted for most of the explained variability in plasma viscosity within subjects (combined adjusted r2 = 65.5%). Logarithm-transformed triglyceride, leukocyte count and serum globulin together contributed an additional 3.0% of the variance in plasma viscosity. Serum total protein, In triglycerides and leukocyte count decreased significantly across higher quartiles of predicted VO2max (all P < 0.0001), with trends towards lower fibrinogen and globulin concentrations (P = 0.054 and P = 0.050, respectively). Higher levels of adiposity were also significantly associated with higher levels of serum total protein (P < 0.0001), globulin (P < 0.0001), fibrinogen (P < 0.01), leukocyte count (P < 0.05), and triglycerides (P < 0.0001). The association of lifestyle factors with the biochemical predictors of plasma viscosity may result directly from a pro-inflammatory state of adipose tissue origin and/or a larger plasma volume related to higher levels of cardiorespiratory fitness. Randomised controlled trials of the effects of regular physical activity of different intensities on plasma viscosity, with reference to body composition, are now required.

Adult↗

The relationship between body weight and plasma viscosity in hypertensive diabetic Nigerians.

Plasma viscosity and fibrinogen concentrations were measured in 70 diabetics (35 hypertensive and 35 normotensive) and compared with those of 35 age- and sex-matched normotensive healthy subjects in relation to body weight. The body weight, body mass index, blood pressure (systolic and diastolic), mean arterial pressure, plasma viscosity and fibrinogen level of the hypertensive diabetics were significantly higher than the values seen in the controls. Among the normotensive diabetics, only the fibrinogen concentration was elevated above that of the controls (P less than 0.01). Body weight, body mass index, blood pressure (systolic and diastolic), mean arterial pressure and plasma viscosity were all significantly higher in the hypertensive diabetics than in their normotensive counterparts. The difference in fibrinogen titre of both groups of diabetics was not significant. Body mass index, fibrinogen and plasma viscosity were correlated significantly with systolic and diastolic blood pressures (P less than 0.001). The order of relative contribution showed that fibrinogen contributed most to blood pressure, followed by plasma viscosity and then body mass index. The results suggest that high levels of body weight, fibrinogen concentration and plasma viscosity could contribute to the development of hypertension in diabetic Nigerians.

Blood Viscosity↗

Physical activity, cardiorespiratory fitness, and the primary components of blood viscosity.

PURPOSE: The relationship of both self-reported leisure time physical activity (LTPA) and predicted maximum oxygen consumption (VO2max) with plasma viscosity and hematocrit (Hct) concentration was examined within a cross-sectional sample of employed middle-aged men. METHODS: Analyses were performed on a subsample of nonsmoking men who completed a preventive medical assessment between 1992-1996. RESULTS: Among nonsmokers the mean age-adjusted levels of plasma viscosity (N = 590) and Hct concentration (N = 632) were significantly lower with higher Physical Activity Index (PAI) categories (P = 0.001 and P = 0.01, respectively). Following adjustment for conventional IHD risk factors and blood leukocyte count, a significant inverse relationship remained for Hct (P = 0.044) but not plasma viscosity. Mean age-adjusted plasma viscosity and Hct concentration also showed a significant decrease with higher quartiles of predicted VO2max (mL x kg(-1) x min(-1))(P = < 0.00005 and P = 0.0004, respectively). Following adjustment for all confounding variables mean plasma viscosity and Hct concentration remained significantly lower with higher quartiles of predicted VO2max (mL x kg(-1) x min(-1))(P = < 0.00005 and P = 0.047). CONCLUSIONS: These data confirm the inverse relationship between LTPA and/or predicted VO2max with plasma viscosity and Hct concentration within nonsmoking middle-aged men of high socioeconomic status.

Adult↗

Experimental evaluation of in vitro stability of purified polydimethylsiloxanes (silicone oil) in viscosity ranges from 1000 to 5000 centistokes.

One of the main problems in the clinical use of silicone oil in vitreoretinal surgery is the instability of the material in terms of emulsification. Fine silicone oil droplets can cause a secondary glaucoma by blocking aqueous outflow. Intravitreally applicable silicone oils comprise an inhomogeneous group of materials, and the rate of emulsification depends on the physicochemical properties of the silicone oils. Clinically most frequently used silicone oils are highly purified polydimethylsiloxanes with a viscosity of 1000 centistokes (cs) to 5000 cs. Low-viscosity silicone oils are preferred by some surgeons because of easier surgical handling and easier removal out of the vitreous. The authors investigated highly purified polydimethylsiloxanes in viscosity ranges of 1000 cs, 2000 cs, 3000 cs, 4000 cs, and 5000 cs with regard to their in vitro stability to evaluate the optimal range of viscosity with acceptable material stability. The comparative stability tests were performed with 0.1% salt solutions of albumin, acidic alpha-1-glycoprotein, fibrin, fibrinogen, gamma globulins, and very-low-density lipoprotein as emulsifiers. Silicone oil at 5000 cs was in all cases distinctly more stable than the silicone oils with a viscosity up to 4000 cs. A positive correlation between the degree of viscosity and an increase of material stability was not found with all emulsifiers. When very-low-density lipoprotein, albumin, and fibrin served as detergents, a remarkable stability gain was achieved only at 5000 cs.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

The clinical relevance of plasma viscosity in Hodgkin's disease.

The erythrocyte sedimentation rate has previously been identified as an important prognostic factor in Hodgkin's disease. The plasma viscosity has replaced the ESR measurement in many laboratories, but doubts exist about its clinical relevance. In this study plasma viscosity at presentation/diagnosis was studied in 107 patients with Hodgkin's disease. A multivariate analysis of factors influencing prognosis and relapse-free survival identified plasma viscosity and number of disease sites as being highly significant. The risk of relapse increases initially with a rise in plasma viscosity, but after a value of about 2.0 mPa.s no further increase in risk is observed. When all of the prognostic factors are made available to the proportional hazards model, treatment modality and plasma viscosity are selected as the best set for predicting time to first relapse. This study demonstrates that measurement of plasma viscosity at presentation is an important prognostic factor in Hodgkin's disease, in terms of predicting outcome or risk of relapse.

Adult↗

Intrinsic viscosity of ovomucoid in random coil conformation.

Ovomucoid is denatured by concentrated solutions of guanidine hydrochloride. The intrinsic viscosities of the glycoprotein in 6 M guanidine hydrochloride in the absence and presence of beta-mercaptoethanol were found to be 8.1 and 16.0 ml/g, respectively. Ovomucoid with disulphide bonds reduced exists in linear random coil conformation. However, the intrinsic viscosity of the randomly coiled protein was less than that predicted from the empirical equations describing the molecular weight dependence of intrinsic viscosities of random coil proteins in 6 M guanidine hydrochloride. On excluding the carbohydrate content of the protein, which is theoretically justified, the calculated intrinsic viscosity interestingly became closer to the measured one. The temperature dependence of the intrinsic viscosity of ovomucoid in linear random coil conformation was studied in the temperature range, 25-55 degrees. The features of the intrinsic viscosity-temperature profile are not comparable with those exhibited by other linear random coil proteins in 6 M guanidine hydrochloride.

Chemical Phenomena↗

Viscosity-dependent locomotion of oral spirochetes.

Spirochetes are thought to remain motile in environments (such as intercellular spaces) that immobilize extracellularly flagellated eubacteria. This attribute suggests that the viscosity of the milieu is of importance to locomotion. We sought to determine the interdependence of oral spirochete locomotion with media viscosity. Video time-lapse microscopy using darkfield optics was used. The motility of the spirochetes in media of different viscosities (various concentrations of Noble agar) was measured. Treponema denticola exhibited the fastest speed (18.7 +/- 4.4 microns/min) at a viscosity of 30 mPa.s. The highest speeds for Treponema vincentii and Treponema socranskii were 41.9 +/- 14.9 and 33.4 +/- 13.2 microns/min, respectively, at 88 mPa.s. These data show that optimal migration of spirochetes is viscosity-dependent. The results support the hypothesis that such viscosity-dependent locomotion could be a virulence factor that enables oral spirochetes to initiate and sustain periodontal disease.

Cell Movement↗

Increased whole blood viscosity on cooling in a patient with cold hemoagglutinin disease.

The whole blood and plasma viscosities have been evaluated in a patient with cold hemoagglutinin disease at different temperatures and at different shear rates. At 37 and 42 degrees C, whole blood viscosity values, regardless of the shear rate applied, resulted to be correspondent to the hematocrit value (31%). The values observed were similar to those noted in a patient with chronic bleeding anemia and an approximately equivalent hematocrit (33%). The same was true for plasma viscosity. At 32 degrees C, whole blood viscosity, regardless of the shear rate, resulted to be higher than expected. The values observed were similar to those noted in a normal subject with a clearly higher hematocrit value (44%) and definitely higher than those noted in the chronic anemia patient. On the contrary, plasma viscosity remained unchanged. These studies indicate that in cold hemoagglutinin disease, red cell aggregation and piling are capable of increasing blood viscosity.

Aged↗

Investigation of flow behaviour (viscosity) from human seminal fluid with a rotational viscosimeter.

Flow behaviour of human seminal fluid was studied with a rotational viscometer (Rotoviso RV 100 with low shear sensor CV 100 made by Haake Karlsruhe) regarding normozoospermia, oligozoospermia, azoospermia and initially prolongated liquefaction time. Measurement is done according to DIN 53018 (procedure) and DIN 53019 (evaluation) and viscosity is given in millipascal seconds (mPas). At a shear rate of 90 s-1 the absolute viscosity n is 7.86 +/- 5.51 mPas (n = 104); without the initial viscous ejaculate (n = 23) viscosity n at 90 s-1 was 5.55 +/- 1.71 mPas (n = 81). Within the group of viscous ejaculates the average viscosity is distinctly higher than the one in the group of normal ejaculates. In both groups there is no correlation between number of spermatozoa and viscosity and motility and viscosity. A reason for the different flow behaviour is not yet found.

Adult↗