Bilateral simultaneous acute angle closure glaucoma triggered by an over-the-counter cold and influenza medication.

A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management.

Green highly sensitive and selective spectroscopic detection of guaifenesin in multiple dosage forms and spiked human plasma.

Guaifenesin (GUA) is determined in dosage forms and plasma using two methods. The spectrofluorimetric technique relies on the measurement of native fluorescence intensity at 302 nm upon excitation wavelength "223 nm". The method was validated according to ICH and FDA guidelines. A concentration range of 0.1-1.1 µg/mL was used, with limit of detection (LOD) and quantification (LOQ) values 0.03 and 0.08 µg/mL, respectively. This method was used to measure GUA in tablets and plasma, with %recovery of 100.44% ± 0.037 and 101.03% ± 0.751. Furthermore, multivariate chemometric-assisted spectrophotometric methods are used for the determination of GUA, paracetamol (PARA), oxomemazine (OXO), and sodium benzoate (SB) in their lab mixtures. The concentration ranges of 2.0-10.0, 4.0-16.0, 2.0-10.0, and 3.0-10.0 µg/mL for OXO, GUA, PARA, and SB; respectively, were used. LOD and LOQ were 0.33, 0.68, 0.28, and 0.29 µg/mL, and 1.00, 2.06, 0.84, and 0.87 µg/mL for PARA, GUA, OXO, and SB. For the suppository application, the partial least square (PLS) model was used with %recovery 98.49% ± 0.5, 98.51% ± 0.64, 100.21% ± 0.36 & 98.13% ± 0.51, although the multivariate curve resolution alternating least-squares (MCR-ALS) model was used with %recovery 101.39 ± 0.45, 99.19 ± 0.2, 100.24 ± 0.12, and 98.61 ± 0.32 for OXO, GUA, PARA, and SB. Analytical Eco-scale and Analytical Greenness Assessment were used to assess the greenness level of our techniques.

Propofol-sparing and hemodynamic effects of guaifenesin in sheep.

OBJECTIVE: To evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep. STUDY DESIGN: Prospective, blinded, two-way crossover experimental study. ANIMALS: Thirteen healthy adult female sheep. METHODS: Anesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg-1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg-1 min-1). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student's t-test. Values of p < 0.05 were considered statistically significant. RESULTS: The propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg-1) than in the SAL treatment (5.94 ± 1.09 mg kg-1). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Guaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range.

Two green and sensitive spectrofluorimetric approaches for determination of Ambroxol and guaifenesin in their single and combined pharmaceutical formulations.

Ambroxol hydrochloride (AMX) and guaifenesin (GFN) are approved drugs utilized to treat coughs through their potent mucolytic and expectorant properties. Due to their massive, combined administration in many illnesses, there is a persistent need for their concurrent estimation in different pharmaceutical formulations. Two sensitive, environmentally friendly spectrofluorimetric methods were developed. AMX was determined using the first method (I) without interference from GFN. This method depends on the quenching of Erythrosine B (EB) native fluorescence at 552 nm after excitation at 527 nm due to the formation of a non-fluorescent AMX-EB ion-pair complex in Britton-Robinson buffer (BRB) solution pH (3.5). The concentration plot is linear over the 0.25-5.0 µg/mL range, with a mean percent found value of 99.74%. Method (II) depends on measuring the native fluorescence of aqueous GFN solution at two analytical wavelengths, either 300 or 600 nm, after excitation at 274 nm. Relative fluorescence intensity (RFI)-concentration plots are linear over the ranges of 0.02-0.5 and 0.1-2.0 µg/ml, with mean percent found at 99.96% and 99.91% at dual wavelengths, respectively. The proposed methods were successfully applied to assay both drugs in raw materials and different single and combined pharmaceutical formulations. These methods have been thoroughly validated following International Committee on Harmonisation (ICH) guidelines. National Environmental Methods Index, Analytical Eco-Scale, and Green Analytical Procedure Index were used to prove greenness, thereby enhancing their applicability. The proposed techniques provide straightforward, precise, and cost-effective solutions for routine formulation analysis in quality control laboratories.

Fast concurrent determination of guaifenesin and pholcodine in formulations and spiked plasma using first derivative synchronous spectrofluorimetric approach.

Guaifenesin and pholcodine are frequently co-formulated in certain dosage forms. A new fast first derivative synchronous spectrofluorometric method has been used for their simultaneous analysis in mixtures. Here, first derivative synchronous spectrofluorometry enabled the successful simultaneous estimation of guaifenesin at 283 nm and pholcodine at 275 nm using a wavelength difference (Δλ) of 40 nm. The method was fully validated following International Council of Harmonization guidelines. For guaifenesin and pholcodine, linearity was determined within the corresponding ranges of 0.05-0.30 and 0.10-6.0 µg/ml. The two drugs were effectively analyzed using the developed approach in their respective formulations, and the results showed good agreement with those attained using reference methods. The method demonstrated excellent sensitivity, with detection limits down to 0.007 and 0.030 µg/ml and quantitation limits of 0.020 and 0.010 µg/ml for guaifenesin and pholcodine, respectively. Therefore, the procedure was successful in determining these drugs simultaneously in vitro in spiked plasma samples and syrup dosage form. The developed methodology also offered an environmentally friendly advantage by utilizing water as the optimal diluting solvent throughout the whole work. Different greenness approaches were investigated to ensure the method's ecofriendly properties.

Resolving phenylephrine HCl and guaifenesin enantiomers on cellulose-based chiral stationary phases: Separation of four enantiomers on 50-mm column.

Chiral high performance liquid chromatographic technique usually employs polysaccharide-based stationary phases in a normal phase mode. This frequently generates large waste of organic solvents. Using shorter columns of 50 mm length as well as a mobile phase with a high water percentage are common approaches for greening this analytical technique. In this context, a new chiral chromatographic technique was developed for simultaneous enantio-separation of phenylephrine HCl and guaifenesin racemates. Four 50 mm cellulose-based columns were experimented to separate the four enantiomers in a reversed phase mode. A face centered design was then employed to optimize the mobile phase acetonitrile% and flow rate on Lux Cellulose-1 (50 × 4.6 mm, 5 µm). The simultaneous resolution of the cited drugs enantiomers was achieved using acetonitrile-water (30:70, by volume), with a flow rate of 0.5 ml min-1 . These optimized chromatographic conditions separate the enantiomers in 7 min running time, generating about 1.0 ml acetonitrile per run. The proposed method was favorably compared with other reported chiral ones in terms of waste volume generated and analysis time required.

Vanillin Production Pathways in Alkaline Nitrobenzene Oxidation of Guaiacylglycerol-ß-guaiacyl Ether.

Alkaline nitrobenzene oxidation (AN oxidation) is a significant method for chemical analysis of lignin. Despite its importance in lignin chemistry, the detailed chemical reactions involved in AN oxidation are not yet fully understood. Surprisingly, there is almost no experimentally supported information available regarding the reaction pathways in the AN oxidation of guaiacyl glycerol-ß-guaiacyl ether (GG), a common model compound in lignin chemistry. This study reports the results of our investigation into the formation pathway of vanillin (4-hydroxy-3-methoxybenzaldehyde) in the AN oxidation of GG. Our series of experiments proposed a vanillin formation pathway involving an enol ether with a C2 side chain, 2-methoxy-4-[2-(2-methoxyphenoxy)-ethenyl]-phenol C2EE, as an intermediate, in which C2EE is produced by the non-oxidative degradation of GG by alkali. Another enol ether with a C3 side-chain, Z-4-[3-hydroxy-2-(2-methoxyphenoxy)-1-propen-1-yl]-2-methoxyphenol (C3EE), and the condensation products formed under alkaline conditions were found to be insignificant as vanillin sources. On the other hand, the comparison of the vanillin yields from GG and isolated C2EE (80.7 and 86.5 mol %, respectively) in their AN oxidation to the C2EE yield from GG in the absence of nitrobenzene (69.9 mol %) also suggested that the vanillin formation from GG involved unknown pathways in which C2EE is not an intermediate.

[Evaluation of the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol versus a fixed-dose combination of bromhexine/guaifenesin/salbutamol in the treatment of productive cough in adult patients with acute bronchitis].

AIM: To evaluate the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol, oral solution, versus Ascoril Expectorant, syrup (combination of bromhexine, guaifenesin, and salbutamol) in the treatment of productive cough in adult patients with acute bronchitis. MATERIALS AND METHODS: This open-label, randomized, phase III study included patients with acute bronchitis who had a productive cough with difficulty in sputum expectoration. 244 patients were randomized in a 1:1 ratio and received 10 mL of the study drug or reference drug 3 times daily for 2 weeks. After 7 and 14 days of treatment, the physician evaluated patient's subjective complaints and the efficacy of therapy. The primary endpoint was the proportion of patients with high and very high efficacy. RESULTS: The primary endpoint was reached by 70 (0.5738) patients in the study drug group and 54 (0.4426) in the reference drug group (p=0.04). The intergroup difference was 0.1311 [95% confidence interval: 0.0057; 0.2566]. The lower limit of the 95% confidence interval was above zero, which confirms the superiority of therapy with the study drug over therapy with Ascoril Expectorant. The proportion of patients with a 1-point total score reduction and with complete resolution of all symptoms according to the Modified Cough Relief and Sputum Expectoration Questionnaire after 7 and 14 days was numerically higher in the study drug group versus the reference drug group. There were no statistically significant differences between the groups in the incidence of adverse events. CONCLUSION: The efficacy of a new combination drug containing ambroxol, guaifenesin, and levosalbutamol in the treatment of productive cough in adult patients with acute bronchitis is superior to the efficacy of Ascoril Expectorant. The safety profiles of the study drug and the reference drug were comparable.

The effect of oral guaifenesin on pediatric chronic rhinitis: A pilot study.

OBJECTIVES: To investigate the effectiveness of guaifenesin in the relief of nasal symptoms in children with chronic rhinitis (CR). We hypothesized that guaifenesin use over a 14-day study period would improve subjective nasal complaints in pediatric patients with chronic rhinitis, as measured by the SinoNasal-5 (SN-5) survey. We also hypothesized improvement in nasal volume and cross-sectional area with guaifenesin. STUDY DESIGN: Randomized, placebo-controlled, parallel group, masked clinical trial. METHODS: The study consisted of a 14-day, randomized, placebo-controlled, parallel group, masked clinical trial of oral guaifenesin for CR in children aged 7-18 years. A 2:1 ratio of subjects on active medication to placebo was used. The study was approved by the Western Institutional Review Board. On initial enrollment and at the conclusion of therapy, the SN-5 was completed by parents, acoustic rhinometry measurements performed, and mucus sampling for rheology was obtained. RESULTS: 30 subjects were enrolled in the study, with 20 receiving guaifenesin and 10 placebo. Treatment with guaifenesin for 14 days produced a significant mean change towards clinical improvement in SN-5 scores compared with placebo (p = 0.013). There was no significant difference in quality of life assessment scores between the two groups or in any of the acoustic rhinometry parameters. Many of the study subjects had difficulty producing a mucus sample sufficient for analysis. CONCLUSIONS: Based upon our pilot data, it appears that guaifenesin treatment may produce objective improvements in pediatric patients with CR. Further research with larger samples sizes, inclusion of children younger than 6, and biophysical mucus analyses is warranted. LEVEL OF EVIDENCE: Level 2b.

Heart rate, arterial pressure and propofol-sparing effects of guaifenesin in dogs.

OBJECTIVE: To evaluate the heart rate (HR) and systemic arterial pressure (sAP) effects, and propofol induction dose requirements in healthy dogs administered propofol with or without guaifenesin for the induction of anesthesia. STUDY DESIGN: Prospective blinded crossover experimental study. ANIMALS: A total of 10 healthy adult female Beagle dogs. METHODS: Dogs were premedicated with intravenous (IV) butorphanol (0.4 mg kg-1) and administered guaifenesin 5% at 50 mg kg-1 (treatment G50), 100 mg kg-1 (treatment G100) or saline (treatment saline) IV prior to anesthetic induction with propofol. HR, invasive sAP and respiratory rate (fR) were recorded after butorphanol administration, after guaifenesin administration and after propofol and endotracheal intubation. Propofol doses for intubation were recorded. Repeated measures analysis of variance (anova) was used to determine differences in propofol dose requirements among treatments, and differences in cardiopulmonary values over time and among treatments with p < 0.05 considered statistically significant. RESULTS: Propofol doses (mean ± standard deviation) for treatments saline, G50 and G100 were 3.3 ± 1.0, 2.7 ± 0.7 and 2.1 ± 0.8 mg kg-1, respectively. Propofol administered was significantly lower in treatment G100 than in treatment saline (p = 0.04). In treatments G50 and G100, HR increased following induction of anesthesia and intubation compared with baseline measurements. HR was higher in treatment G100 than in treatments G50 and saline following induction of anesthesia. In all treatments, sAP decreased following intubation compared with baseline values. There were no significant differences in sAP among treatments. fR was lower following intubation than baseline and post co-induction values and did not differ significantly among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: When administered as a co-induction agent in dogs, guaifenesin reduced propofol requirements for tracheal intubation. HR increased and sAP and fR decreased, but mean values remained clinically acceptable.

High throughput virtual screening strategy to develop a potential treatment for bronchial asthma by targeting interleukin 13 cytokine signaling.

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of -3.84 and -3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma.

Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation.

Combinatorial drug therapy has attracted substantial attention as an emerging strategy for the treatment of diseases with complex pathological mechanisms. We previously developed a potentially universal computational screening approach for combination drugs and used this approach to successfully identify some beneficial combinations for the treatment of heart failure. Herein, this screening approach was used to identify novel combination drugs for the treatment of epilepsy in an approved drug library. The combination of guaifenesin-andrographolide was first discovered as a promising therapy with synergistic anticonvulsant activities in maximal electroshock (MES)- and subcutaneous pentylenetetrazol (sc-PTZ)-induced epilepsy models in vivo. The studies of network analysis, fluorescence imaging, and N-methyl-d-aspartate (NMDA)-induced cytotoxicity further revealed that guaifenesin-andrographolide might synergistically affect NMDA receptors and then alleviate the pathogenesis of epilepsy. Therefore, we report that the combination of guaifenesin-andrographolide exerts effects against epilepsy through a novel synergistic mechanism and is thus a potential treatment for epilepsy, providing a promising mechanism for the design of novel combinatorial drug treatments against epilepsy.

A Chemometric Strategy in the Development of a RP-UPLC Method for the Quantitative Resolution of a Two-Component Syrup Formulation.

A novel chemometric strategy was implemented in the development of a new ultraperformance liquid chromatography method for the quantitative estimation of guaifenesin and pseudoephedrine hydrochloride in a two-component syrup formulation with minimal experimental effort, time and reagent. A full factorial design with three factors was investigated to find optimal working conditions of chromatographic factors (column temperature, flow rate, and 0.1 M H3PO4% in mobile phase) that affect the chromatographic separation. Then, optimum experimental conditions providing adequate separation of the analyzed drug substances within the short runtime were determined. Under optimal experimental conditions, the retention times for guaifenesin and pseudoephedrine hydrochloride were obtained as 0.817 and 1.430 min, respectively. In the optimized RP-UPLC method, chromatographic response was reported as a linear function of concentration between 5.0 and 80.0 µg/mL for guaifenesin and 10.0-90.0 µg/mL for pseudoephedrine hydrochloride. The proposed method was carefully validated and successfully applied to quality control and analysis of a cough syrup preparation containing guaifenesin and pseudoephedrine hydrochloride. Consequently, the proposed reversed-phase ultraperformance liquid chromatography method provided an opportunity to quantify relevant drugs with small amount of reagents and short runtime.