Artificial Neural Networks and Concentration Residual Augmented Classical Least Squares for the Simultaneous Determination of Diphenhydramine, Benzonatate, Guaifenesin and Phenylephrine in their Quaternary Mixture

Purpose: To develop two multivariate calibration methods for the simultaneous spectrophotometric determination of a quaternary mixture composed of diphenhydramine HCl, benzonatate, guaifenesin and phenylephrine HCl in Bronchofree ™ capsules in the ratio of 2.5 : 10 : 10 : 1, respectively.Methods: Novel artificial neural networks (ANNs) and concentration residual augmented classical least squares (CRACLS) methods were developed for the quantitative determination of the quaternary mixture. For proper analysis, a four-level, four-factor experimental design was established resulting in a training set of 16 mixtures containing different ratios of the four analytes. A validation set consisting of six mixtures was used to validate the prediction ability of the suggested models.Results: ANNs and CRACLS methods were successfully applied for the analysis of raw materials and capsules. For ANNs method, % recovery of diphenhydramine HCl, benzonatate, guaifenesin and phenylephrine HCl in the capsules was 102.21 ± 1.34, 100.30 ± 1.17, 99.31 ± 2.00 and 98.50 ± 1.27, respectively. On the other hand, % recovery of the four analytes by CRACLS was 99.84 ± 2.22, 100.07 ± 0.63, 98.37 ± 1.42 and 97.99 ± 0.96, respectively.Conclusion: The proposed methods can be applied for the quantitative determination of the four components without interference from excipients, thus obviating the need for preliminary extraction of analytes from the pharmaceutical formulation. The ability of the methods to deconvolute the highly overlapped UV spectra of the four components’ mixtures using low-cost and easy-to-handle instruments such as UV spectrophotometer is also an advantage.Keywords: Artificial neural networks, Concentration residual augmented classical least squares, Quaternary mixture, Simultaneous determinatio

Effects of sulfur and nitrogen on nutrients uptake of corn using acidified water

A greenhouse experiment was carried out with elemental sulfur (S) and nitrogen (N) fertilizer using acidified water (pH 6.5) to determine nutrients uptake and growth of maize plants grown in calcareous sandy soil. Four levels of elemental sulfur (0, 1, 5 and 10 t ha-1), two levels of N (0 and 0.34 t N ha-1) were tested at Al Foah Agricultural Experiment Farm, United Arab Emirates (UAE) University. In Al Semaih soil, the pH (1.21-1.33) and electrical conductivity (EC) (7.61 dSm-1) decreased by application of elemental S plus N, while EC rose (3.84 dSm-1) and pH reduced (1.20 to 1.11) in Al Zaid soil. Acidity improved by decreasing soil pH, Na and Cl concentration in both soils. A significant change was observed by application of acidified water at Al Semaih soil causing high levels in the initial status of EC, Na and Cl concentrations in the soil. A negative relationship was observed with soil pH among N, P, S, Fe, Zn and Mn, while uptake availability of sulfur and nitrogen had positive relationship with all nutrients. Elemental sulfur at the rate of 5 t ha-1 and nitrogen had a significant contribution towards uptake availability of N, P, S, Fe, Zn and Mn in both Al Zaid and Al Semaih soils. Based on experimental findings, elemental S at the rate of 5 tha-1 and N fertilizer (0.34 t ha-1) is suitable for the growth of maize at both soils. Al Zaid soil possesses advantages over Al Semaih soil due to its high nutrient uptake ability.Key words: Calcareous soil, corn, elemental sulfur, nitrogen, nutrients uptake

Growth and nutrient uptake of maize plants as affected by elemental sulfur and nitrogen fertilizer in sandy calcareous soil

This study was carried out to investigate the effect of elemental sulfur (S0) combined with or without N fertilizer on the growth and nutrient uptake such as nitrogen (N), phosphorus (P), sulfur (S), iron (Fe), zinc (Zn) and manganese (Mn) by maize plants grown in sandy calcareous soils. Elemental S at rates of 0, 1, 5 and 10 t ha-1 were tested combined with or without N fertilizer at rates of 0 and 0.34 t ha-1 in pots using normal irrigation water (pH >7.5) under Al Zaid and Al Semaih soils in evaporative cooled greenhouse conditions. Electrical conductivity (EC) increased (2.50 to 2.95 dSm-1) significantly and decreased (5.07 to 6.06 dSm-1) with application of S0 at rates of 5 and 10 t ha-1 combined with N fertilizer in both Al Zaid and Al Semaih soils, respectively. Soil acidity improved by decreasing soil pH (1.41 to1.52 unit) with application of S0 at the rate of 10 t ha-1 combined with N fertilizer. Addition of S0 at the rate of 5 t ha-1 combined with N fertilizer recorded superior total dry matter (TDM) and maximum uptake of all nutrients in both soils. Total dry matter accumulation and nutrient uptake had positive correlation, while soil pH showed negative correlation with TDM and uptake of all nutrients. Based on experimental findings, S0 at the rate of 5 t ha-1 combined with N fertilizer is suitable for growth of maize in both soils. Collectively, the results indicate that Al Zaid soil is more favorable due to higher nutrient uptake and growth of maize than Al Semaih soil.Key words: Elemental sulfur, nutrient uptake, maize, sandy calcareous soil

Development and validation of stability indicating method for determination of sertraline following ICH guidlines and its determination in pharmaceuticals and biological fluids

<p>Abstract</p> <p>Background</p> <p>Sertraline is a well known antidepressant drug which belongs to a class called selective serotonin reuptake inhibitor. Most published methods do not enable studying the stability of this drug in different stress conditions.</p> <p>Results</p> <p>Two new methods were developed for the determination of sertraline (SER). Both methods are based on coupling with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.8 and measuring the reaction product spectrophotometrically at 395 nm (Method I) or spectrofluorimetrically at 530 nm upon excitation at 480 nm (Method II). The response-concentration plots were rectilinear over the range 2-24 μg/mL and 0.25-5 μg/mL for methods I and II respectively with LOD of 0.18 μg/mL and 0.07 μg/mL, and LOQ of 0.56 μg/mL and 0.21 μg/mL for methods I and II, respectively.</p> <p>Conclusion</p> <p>Both methods were applied to the analysis of commercial tablets and the results were in good agreement with those obtained using a reference method. The fluorimetric method was further applied to the in vivo determination of SER in human plasma. A proposal of the reaction pathway was presented. The spectrophotometric method was extended to stability study of SER. The drug was exposed to alkaline, acidic, oxidative and photolytic degradation according to ICH guidelines. Moreover, the method was utilized to investigate the kinetics of oxidative degradation of the drug. The apparent first order rate constant and t_1/2of the degradation reaction were determined.</p

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was USD 92 492 million using approach 1 and USD 73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was USD 95 004 million using approach 1 and USD 75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially.publishedVersio

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly