Effects of recycled waste on the modulus of elasticity of structural concrete.

Concrete, the construction industry's most utilized construction material, has transformed the environment and the modern built-up lifestyle. Although concrete is a first-rate supplier to the carbon footprint, it is imperative for buildings to display sustainable characteristics. Scholars have explored techniques to lessen the carbon footprint and the way to put into effect strategic waste control plans in which waste is reused. This study explores the dual benefits wherein concrete ingredients are replaced through abandoned waste which reduces the unwanted waste materials that have a substantial carbon footprint and thus results in the recycling of waste as part of a sustainable economic system. In this study, timber ash is utilized as a partial substitute for sand and cement, crumb rubber and waste glass as a partial substitute for sand, recycled concrete, and waste glass as a substitute for gravel. Characteristics studies were done to check the influence of each waste replacement on the modulus of elasticity of concrete. More than sixty-five combinations of waste have been examined to attain the modulus of elasticity of concrete. A total of about 200 concrete cylinders were cast to provide at least three cylinders for each generated data point. Three different ASTM standards were utilized to determine the modulus of elasticity of each mix. Four mixes comprising of the combination of two waste materials and two mixes comprising of the combination of three waste materials replacing natural materials were determined to exhibit an equal or superior modulus of elasticity of the control mix of 25 GPa.

Dimensionality and reliability of USM pre-clinical medical students' guidance and counselling needs questionnaire.

OBJECTIVE: There is no standard mechanism for empathy guidance and counselling for medical students. This study aimed to determine the dimensionality and reliability of a questionnaire developed for establishing guidance and counselling for pre-clinical medical students at Universiti Sains Malaysia (USM). METHODS: A cross-sectional study was conducted among undergraduate medical students of the School of Medical Sciences of USM. The proposed USM Medical Students' Guidance and Counselling Needs (USM-MSGCN) questionnaire is a self-administered instrument that consists of 68 initial items developed from the recommendation of medical students, counsellors, and lecturers in the medical education department. To determine the dimensionality (construct validity) and reliability of the questionnaire, exploratory factor analysis and Cronbach's alpha internal consistency reliability analysis were conducted. RESULTS: A total of 208 students participated in the study. Factor analysis revealed that the items were not unidimensional; four potential constructs could be extracted from the questionnaire, namely, self-leadership (7 items), communication (5 items), learning (5 items), and psychological coping skills (3 items), with factor loading ranges of 0.56-0.82, 0.56-0.88, 0.65-0.84, and 0.79-0.80, respectively. These domains had the following internal consistency reliability (Cronbach's alpha): 0.89, 0.90, 0.87, and 0.87, respectively; the overall alpha value was 0.93. CONCLUSION: Four factors, with 20 items in the USM-MSGCN questionnaire had good validity and reliability values when administered among the pre-clinical medical students.

Saliva versus Plasma Relative Bioavailability of Tolterodine in Humans: Validation of Class III Drugs of the Salivary Excretion Classification System.

Relative bioavailability study of tolterodine in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioavailability and bioequivalence of class III drugs according to the salivary excretion classification system (SECS). Saliva and plasma samples were collected up to 16 h after 2 mg oral dose. Saliva and plasma pharmacokinetic parameters were calculated by non compartmental analysis using Kinetica program V5. Human effective intestinal permeability was optimized by SimCYP program V13. Tolterodine falls into class III (High permeability/Low fraction unbound to plasma proteins) and hence was subjected to salivary excretion. A high pearsons correlation coefficient of 0.97 between mean saliva and plasma concentrations, and saliva/plasma concentrations ratio of 0.33 were observed. In addition, correlation coefficients and saliva/plasma ratios of area under curve and maximum concentration were 0.98, 0.95 and 0.42, 0.34 respectively. On the other hand, time to reach maximum concentration was higher in saliva by 2.37 fold. In addition, inter subject variability values in saliva were slightly higher than plasma leading to need for slightly higher number of subjects to be used in saliva studies (55 vs. 48 subjects). Non-invasive saliva sampling instead of invasive plasma sampling method can be used as a surrogate for bioavailability and bioequivalence of SECS class I drugs when adequate sample size is used.

In silico vs. in vivo human intestinal permeability.

The aim of this research is to calculate human intestinal permeability in silico and correlate results with those measured in vivo. Optimized human intestinal permeability values were calculated for 16 drugs by de-convolution of human plasma profiles using Parameter Estimation module of SimCYP program V13. Results showed high in silico-in vivo correlation coefficient of 0.89 for drugs with high/low permeability values. In silico permeability, if properly optimized, can be used as surrogate for in vivo permeability for BCS class I drugs and hence is suggested that such methodology could be employed as a support for waiver of in vivo studies.

Liquid chromatographic-electrospray mass spectrometric determination of cyclosporin A in human plasma.

A rapid, sensitive and selective liquid chromatography-mass spectrometry (LC-MS) assay has been developed for determination of cyclosporin A (CyA) in human plasma; cyclosporin B (CyB) was used as internal standard (IS). The method utilized a combination of a column-switching valve and a reversed-phase symmetry column. The mobile phase was a 25:75 (v/v) mixture of 10% aqueous glacial acetic acid and acetonitrile. Running time per single run was less than 10 min. Sample preparation included C8 SPE of human plasma spiked with the analyte and internal standard, evaporation of the eluate to dryness at 50 degrees C under N2 gas, and finally reconstitution in the mobile phase. Detection of cyclosporin A and the IS was performed in selected ion-monitoring mode at m/z 601.3 and 594.4 Da for CyA and IS, respectively. Quantitation was achieved by use of the regression equation of relative peak area of cyclosporin to IS against concentration of cyclosporin. The method was validated according to FDA guideline requirements. The linearity of the assay in the range 5.0-400.0 ng mL(-1) was verified as characterized by the least-squares regression line Y = (0.00268+/-1.9 x 10(-4))X+(0.00078+/-1.8 x 10(-3)), correlation coefficient, r = 0.9986+/-1.1 x 10(-3) (n = 48). Intra and inter-day quality-control measurements in the range 5.0-350.0 ng mL(-1) revealed almost 100% accuracy and < or = 9% CV for precision. The mean absolute recovery of CyA was found to be 84.01+/-9.9% and the respective relative recovery was 100.3+/-9.19. The limit of quantitation (LOQ) achieved was 5 ng mL(-1). Eventually, stability testing of the analyte and IS in plasma or stock solution revealed that both chemicals were very stable when stored for long or short periods of time at room temperature or -20 degrees C.

Comparative bioavailability of two cefadroxil products using serum and urine data in healthy human volunteers.

1. The aim of the present study was to assess the bioequivalence of two cefadroxil products, namely Ultracef (a reference product) in the form of a 500 mg capsule (produced by Bristol-Myers Squibb Laboratories, Princeton, NJ, USA) and Roxil (a test product) in the form of a 500 mg capsule (produced by Tabuk Pharmaceutical Manufacturing, Tabuk, Saudi Arabia). 2. The study was performed under US Food and Drug Administration (FDA) guidelines (http://www.fda.gov/cder) on 24 healthy male subjects. Both products were administered orally as a single dose (1 x 500 mg capsule) separated by a 1 week washout period. Following oral administration, blood and urine samples were obtained and analysed for cefadroxil concentrations using a sensitive and specific HPLC assay. 3. There were no statistically significant differences between the two products in either the mean concentration-time profiles or the cumulative urinary excretion of cefadroxil at various times. Similarly, no statistical significance was observed in the pharmacokinetic parameters reflecting rate and extent of drug absorption. The relative extent of drug absorption, assessed by calculating the area under the curve (AUC) ratio for Roxil/Ultracef for 10 h and for infinity was 0.94 with 90% confidence limits (CL) of 0.91-0.98. In agreement with serum data, the average ratio (Roxil/Ultracef) of the cumulative amount of cefadroxil excreted in urine 10 h after the dose was found to be 0.97, with 90% CL of 0.88-1.05. The CL of the AUC and cumulative urinary excretion ratios are within the FDA accepted limits for bioequivalent products (0.80-1.25). 4. These findings show that serum and urine data of cefadroxil are in agreement and indicate that Roxil (the test product) and Ultracef (the reference product) are bioequivalent in terms of the rate and extent of drug absorption.

Liquid chromatographic-mass spectrometric method for quantitative determination of lisinopril in human plasma.

A validated liquid chromatographic-mass spectrometric (LC/MS) method for the determination of lisinopril in human plasma is presented. Enalapril was used as an internal standard. After the addition of internal standard, solid phase extraction was used as a cleaning step. To separate lisinopril and enalapril from interfering endogenous plasma substances, the analysis was performed using column switching valve. The quantitative determination was performed using selected ion monitoring (+)-electrospray LC-MS. A combination of an acidic mobile phase and a reverse phase column was used. A precision in the linear range from 10 to 500.0 ng/mL plasma, absolute recovery of 91.69% for lisinopril and 90.26% for enalapril, stability for 3.5 months at -20 degrees C have been achieved. Limit of quantitation (LOQ) was 10 ng/mL while limit of detection (LOD) was about 1 ng/mL.

Bioequivalence assessment of Azomycin (Julphar, UAE) as compared to Zithromax (Pfizer, USA)--two brands of azithromycin--in healthy human volunteers.

Two studies have been performed to assess the relative bioavailability of Azomycin (Julphar, UAE) as compared with Zithromax (Pfizer, USA) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved Azomycin capsules and the other Azomycin suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of azithromycin were administered as single dose on two treatment days separated by a 2 weeks washout period. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood, was analysed for azithromycin by HPLC coupled with electrochemical detection. Various pharmacokinetic parameters including AUC(0-t,) AUC(0-infinity,) C(max), T(max), T(1/2) and K(elm) were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratios of these parameters were found within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences it was concluded that Azomycin capsule is bioequivalent to Zithromax capsule and Azomycin suspension is bioequivalent to Zithromax suspension.

Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

Adsorption of allopurinol and ketotifen by chitosan.

The experimental work of studying the adsorption of ketotifen and allopurinol by chitosan focused on determining the solubilities and the adsorption isotherms of the adsorbates employed in this study. The adsorption of the aforementioned compounds by chitosan was studied using the rotating bottle method. The concentrations, both before and after the attainment of equilibrium, were determined with the aid of a reversed-phase high-performance liquid chromatography column. The results of these studies demonstrated that ketotifen and allopurinol are both adsorbed by chitosan. The nonlinear Langmuir-like and the Freundlich models both were applied to the experimental data. The correlation coefficients obtained from the nonlinear Langmuir-like model were better than those obtained from Freundlich model, suggesting that allopurinol and ketotifen interacted with certain specific binding sites on the chitosan surface. The allopurinol adsorption experiments indicated that the particle size of chitosan and therefore the surface area can significantly affect the Langmuir capacity constant, while the affinity constants are statistically the same. As expected from the solubility studies, the ketotifen adsorption experiments at 2 different pHs (7 and 10) showed that the adsorption affinity at pH 10 was much higher than at pH 7. What was not expected was that the capacity constants were significantly different, suggesting that further studies are needed using common ion buffers and multicomponent adsorption for the proper mechanism to be determined.

Enhancement of oral absorption of metronidazole suspension in humans.

The purpose of this study was to investigate oral absorption of two metronidazole suspension products, Flagyl((R)) and a test product. Twenty-four healthy volunteers participated in the study. The crossover study was done in a two-phase, two-sequence manner with a 2-week washout period. Individual disposition kinetics were determined by non-compartmental analysis. AUC(0-infinity) and C(max) values were 1.26 and 1.86 times more in the case of test formulation. Mean plasma drug concentrations were analyzed to estimate the rate and extent of oral absorption. The optimized duodenal, jejunal1, jejunal2, illial1, ileal2, ilial3, ilial4, colonic permeability values (x10(-4)) for the test and Flagyl products were 3.96, 3.96, 3. 96, 0.68, 0.37, 0.01, 0.12, 0.38 and 2.34, 0, 0, 1.2, 1.1, 0.9, 0.3, 0.04cm/s, respectively. The total fraction of oral dose absorbed for the test and Flagyl products were 95.5% and 65.6% respectively, consistent with the pharmacokinetic ratios. The test product exhibited significantly higher absorption rate and extent than Flagyl, but both show similar half-lives. Sensitivity analysis showed that drug absorption is sensitive to effective permeability but not sensitive to particle radius and small intestinal transit time. The two products were found bio-inequivalent which is suggested to be due to differences in formulation additives that decreased the effective permeability of Flagyl.

Allergic bronchopulmonary aspergillosis as presenting sign of cystic fibrosis in an elderly man.

BACKGROUND: Although cystic fibrosis is the most common genetic disorder of children, its heterogeneous spectrum of severity lends itself to underdiagnosis in the older adult patient population where the index of suspicion is not high. METHODS: We report a 60-year-old Hispanic man with asthma who presented with progressive dyspnea and wheezing unresponsive to inhaled corticosteroid treatment. Additionally, he had clinical findings and a past history suggestive of cystic fibrosis. Skin testing, radiography and laboratory studies were completed to evaluate for allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. RESULTS: Test results revealed peripheral eosinophilia and hyper IgE. Skin testing to Aspergillus fumigatus (Af) was positive. IgG, IgM, and Af specific antibodies were present. High resolution CT scan showed central bronchiectasis. Sweat tests were positive on two separate occasions and gene analysis showed our patient to have a positive gene mutation at D127ON/D127ON. CONCLUSION: Cystic fibrosis should be suspected in the older adult patient with a compatible clinical presentation.

Formulation and release behavior of diclofenac sodium in Compritol 888 matrix beads encapsulated in alginate.

Sustained-release polymer beads containing diclofenac sodium (DNa) dispersed in Compritol 888 and encapsulated in calcium alginate shell were prepared utilizing 2(3) factorial design. The effect of sodium alginate concentration, drug: Compritol 888 weight ratio and CaCl2 concentration on drug content (%), time for 50% and 80% of the drug to be released, and mean dissolution time (MDT) were evaluated with analysis of variance (ANOVA). An increase in the level of all these factors caused retardation in the release, and t50%, t80%, and MDT were increased. The drug release was dependent on the pH of the release media. A formula that gives a release comparable to commercial products was prepared.

RP-LC method for the determination of cetirizine in serum.

The development and evaluation of HPLC method for quantifying cetirizine in human serum is described. The method involves liquid phase extraction of cetirizine in methylene chloride, adding diazepam as an internal standard, followed by separation on a reversed phase C18 Novapak column (150 x 3.9 nm; 4 microm), and employing a UV-detection set at 230 nm at ambient temperature. The mobile phase consists of a 13 mM phosphoric acid solution and acetonitrile (61:39 v/v) adjusted to pH 2.8 with 5 M NaOH. The assay is linear from 10 to 500 ng ml(-1) with a detection limit of 5 ng ml(-1) and a mean recovery of 96.5%. The applicability of this method in pharmacokinetic studies is evaluated.

Trace-level determination of nifedipine in human serum by reversed phase high performance liquid chromatography.

A rapid, simple, specific and sensitive high performance liquid chromatographic method has been developed for the determination of nifedipine (adalate) in human serum using diazepam (valium) as an internal standard (I.S.). The method utilized a 5 microm nonpolar C18 reversed phase Hypersil (ODS) column (250 x 3 mm i.d.). The mobile phase consisted of 60% v/v, acetonitrile in water, adjusted to pH 3.7 with glacial acetic acid and ammonium acetate, and pumped at a flow rate of 2 ml/min. The effluent was monitored by UV detection at 340 nm and a sensitivity fixed at 0.02 aufs. Each analysis required no longer than 4 min. The minimum detectable amount of nifedipine in serum was 3 ng/ml, and the mean absolute recovery was 93.5%. The within and between-day coefficients of variation at three different concentrations from 15-160 ng/ml ranged from 2.07 to 7.76%, and from 3.15 to 7.98% respectively. Calibration graphs for 10 to 200 ng/ml were linear with a mean correlation coefficient, r (n = 36) of 0.9991. The method was validated for accuracy, sensitivity, selectivity and reproducibility and finally was utilized and proved to be suitable in a bioavailability study of two products of nifedipine following oral administration to healthy male subjects.

Determination of the population pharmacokinetic parameters of sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium by simultaneous data fitting using NONMEM.

Data from sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium are fitted simultaneously using NONMEM and the general linear model, ADVAN 5. Absorption and disposition parameters, serum levels, and absorption profiles were determined. The in vivo absorption profiles were determined using the program TOPFIT. The in vivo absorption for the sustained-release formulation is slow first order and follows a flip-flop model since disposition rate constants are greater than absorption rate constants. Absorption from the enteric-coated form is essentially complete (> or = 95%) at about 7.5 h, while it is 95% complete at 24 h from the sustained-release formulation. This suggests likely absorption from the colon in the case of the sustained-release formulation since absorption is only 75% complete during the first 10 h. The sustained-release relative bioavailability is 90-99%. Absorption from the suppository is essentially complete at about 4.5 h. However, the relative bioavailability of the suppository formulation is low (55%), since defecation may remove the drug from the absorption site before complete absorption.

Imported malaria: a retrospective study in University Hospital, Kuala Lumpur, a ten-year experience.

Over a period of ten years (1983-1992), 134 malaria cases admitted to University Hospital, Kuala Lumpur (UHKL) were analysed. Malays constituted 27.6%, Chinese 29.8%, Indians 9.7%, Indonesians 16.4% and other foreigners 16.4%. Therefore, of the total number of cases, foreigners constituted 32.8% (44) of all the malaria cases admitted to UHKL. Fifteen of these foreigners had chloroquine-resistant strains of malarial parasites. Three species of malaria were reported of which Plasmodium falciparum constituted the most (46.3%) (80% of these developed resistance to chloroquine). Plasmodium vivax was confirmed in 44.8% (10% of these developed resistance to chloroquine) and there was only one case of Plasmodium malarie infection.

Comparative bioavailability of two capsule formulations of mefenamic acid.

Pharmacokinetic behavior of single dose of 2 mefenamic acid capsule formulations was studied in a randomized crossover design in 22 healthy male volunteers. Following ingestion of 250 mg of either of the products, blood samples were obtained over a 14-hour period and the serum drug concentrations were determined by an HPLC assay with ultraviolet detection at 280 nm. The parametric 90% confidence intervals of the mean value of the ratio (fendol (test)/ponstan (reference)) of pharmacokinetic parameters were 0.88-1.07, 0.94-1.19, and 0.89-1.16 for AUC zero-infinity, Cmax and T1/2. In each case values were within the acceptable bioequivalence range of 0.8-1.25. Distribution-free point estimate for the difference in expected medians of Tmax of the 2 formulations (fendol-ponstan) was -0.5 hours with a 90% confidence interval of -1.0 to -0.25 which overlaps with the stipulated bioequivalence range of +/-0.48. The kinetic parameters a comparable to what is reported for mefenamic acid and there were no statistically significant differences in any of them when comparing the 2 products by ANOVA on log-transformed data. Although the 2 products are not equivalent regarding the secondary parameter Tmax, still the data indicate that they could be considered bioequivalent regarding rate of absorption (Cmax), extent of absorption (Cmax and AUC), and elimination (t1/2).

Synthesis and evaluation of some acyloxyethyl mefenamates as possible prodrugs.

Various acyloxyethyl mefanamates were synthesized and evaluated for potential application as prodrugs. Their kinetics of hydrolysis were examined in aqueous solutions of pH 1.0 and 7.4 and in human plasma at 37 degrees C. Among the synthesized compounds, the beta-carboxypropionylethyl mefenamate and the pivaloyloxyethyl mefenamate show high stability against enzymatic and non enzymatic hydrolysis. On the other hand the acetyloxyethyl mefenamate shows t1/2s of 1.4 h, 1.41 h and 3.61 h in human plasma, solutions of pH 7.4 and pH 1.0 respectively; However, its hydrolysis to mefenamic acid in plasma was not quantitative. Preliminary in vivo study shows that acetyloxyethyl mefenamate gave plasma concentration of mefenamic acid lower than that of control after oral administration. The calculated AUC0-inf for the acetyloxyethyl and control were 45 and 85 micrograms.h/ml respectively.

Dissolution kinetics of glibenclamide glass.

This work examines the dissolution kinetics of glibenclamide crystalline state, form I, and glibenclamide glassy state, form II. This required determination of the pH-solubility profiles of the two forms, dissolution at different stirring rates, temperatures, and pHs. It was found that form II exhibited higher solubility and dissolution rate at all the studied pHs. However, a significant increase in dissolution and solubility of form II was noted at pH 6. Dissolution studies at different stirring rates confirmed that the dissolution process is diffusion controlled, zero order in nature and adheres to the Noyes and Whitney and Levich equations. Dissolution studies at different temperatures enabled calculation of the heat of dissolution, Ea, of both forms. Ea for form I and form II was found to be almost identical. Storing of form II for one week at different temperatures resulted in the partial transformation of form II to form I as indicated from dissolution studies. The extent of transformation and hence reduction in dissolution rate increased with the increase in storage temperature.