Academic literature on the topic 'Bromhexina'

Background: Painful peripheral neuropathy is a dose-limiting adverse effect of the antitumor drug oxaliplatin. The main symptoms of neuropathy: tactile allodynia and cold hyperalgesia, appear in more than 80% of patients on oxaliplatin therapy and are due to the overexpression of neuronal sodium channels (Navs) and neuroinflammation. Objective: This study assessed antiallodynic and antihyperalgesic properties of two repurposed drugs with antiinflammatory and Nav-blocking properties (bromhexine and its pharmacologically active metabolite - ambroxol) in a mouse model of neuropathic pain induced by oxaliplatin. Using molecular docking techniques, we predicted targets implicated in the observed in vivo activity of bromhexine. Methods: Oxaliplatin (a single intraperitoneal dose of 10 mg/kg) induced tactile allodynia and cold hyperalgesia in CD-1 mice and the effectiveness of single-dose or repeated-dose bromhexine and ambroxol to attenuate pain hypersensitivity was assessed in von Frey and cold plate tests. Additionally, Veber analysis and molecular docking experiments of bromhexine on mouse (m) and human (h) Nav1.6-1.9 were carried out. Results: At the corresponding doses, ambroxol was more effective than bromhexine as an antiallodynic agent. However, at the dose of 150 mg/kg, ambroxol induced motor impairments in mice. Repeated-dose bromhexine and ambroxol partially attenuated the development of late-phase tactile allodynia in oxaliplatin-treated mice. Only 7-day administration of bromhexine attenuated the development of late-phase cold hyperalgesia. Bromhexine was predicted to be a strong inhibitor of mNav1.6, mNav1.7, mNav1.9, and hNav1.7-hNav1.9. Conclusion: The conversion of bromhexine to other than ambroxol active metabolites should be considered when interpreting some of its in vivo effects. Nav-blocking properties of bromhexine (and previously also predicted for ambroxol) might underlie its ability to attenuate pain caused by oxaliplatin.

Introduction. Multicomponent oral drugs containing salbutamol, bromhexine, ambroxol and guaifenesin have a mucolytic, expectorant and bronchodilator effect. The development method for determination substances in biological fluids is a main procedure for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs. There is no published data of the determination of bromhexine, ambroxol and guaifenesin, but there a lot of published methods for divided determination analytes in a biological fluid. This study presents the development and validation of a method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human blood plasma by high performance liquid chromatography with tandem mass spectrometric detection. A sample preparation was perfomed by solid-phase extraction. Deuterated derivatives were used as internal standards.Aim. The aim of the study is to develop a method for the quantitative determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection for performing the analytical part of pharmacokinetic studies.Materials and methods. Determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection. A sample was prepared using solid-phase extraction.Results and discussion. The method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over and stability.Conclusion. The method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma was developed and validated by HPLC-MS/MS. The analytical range of the was 0.1–20 ng/mL in plasma for salbutamol, 0.25–25 ng/mL in plasma for bromhexine, 0.075–3 ng/mL in plasma for ambroxol, and 10–2000 ng/mL in plasma for guaifenesin. Method could be applied to determination of salbutamol, bromhexine, ambroxol and guaifenesin in plasma for PK and BE studies.

Telah dikembangkan kromatografi cair kinerja tinggi (KCKT) fase balik yang sederhana, akurat, dan presisi untuk menetapkan campuran chlorpheniramin maleat, ephedrin HCl dan bromhexin HCl dalam sediaan sirop. Pemisahan diperoleh dengan menggunakan kolom Eurospher-100 C18 (ODS) 5μm (125 x 3 mm i.d.), dengan fase gerak etanol-asam asetat 0,5% yang dialirkan secara gradien dan detektor ultra violet. Kemampuan sistem memisahkan puncak-puncak analit cukup baik. Metode yang dipakai menghasilkan linieritas pada rentang 84,16–336,64 ppm untuk chlorpheniramin maleat, 160,56-642,24 ppm untuk ephedrin HCl dan 160,68–642,72 ppm untuk bromhexin HCl dengan. Batas kuantitasi ephedrin HCl, bromhexin HCl, dan chlorpheniramin maleat dalam sediaan sirop berturut-turut adalah 98,48; 109,73 dan 330,42 ppm. Akurasi terbaik untuk ephedrin HCl, bromhexin HCl, dan chlorpheniramin maleat dalam matrik sirop berturut-turut 96,83; 98,34 dan 97,24 % dengan presisi terbaik berturut-turut 0,39; 0,35 dan 2,25 %.

Introduction: Bromhexine is a potential therapeutic option in COVID-19, but no data from a randomized clinical trial has been available. The present study aimed to evaluate the efficacy of bromhexine in intensive care unit (ICU) admission, mechanical ventilation, and mortality in patients with COVID-19. Methods: An open-label randomized clinical trial study was performed in Tabriz, North-West of Iran. They were randomized to either the treatment with the bromhexine group or the control group, in a 1:1 ratio with 39 patients in each arm. Standard therapy was used in both groups and those patients in the treatment group received oral bromhexine 8 mg three times a day additionally. The primary outcome was a decrease in the rate of ICU admissions, intubation/mechanical ventilation, and mortality. Results: A total of 78 patients with similar demographic and disease characteristics were enrolled. There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P = 0.006), intubation (1 out of 39 vs. 9 out of 39, P = 0.007) and death (0 vs. 5, P = 0.027) in the bromhexine treated group compared to the standard group. No patients were withdrawn from the study because of adverse effects. Conclusion: The early administration of oral bromhexine reduces the ICU transfer, intubation, and the mortality rate in patients with COVID-19. This affordable medication can easily be administered everywhere with a huge positive impact(s) on public health and the world economy. Altogether, the verification of our results on a larger scale and different medical centers is strongly recommended. Trial Registration: IRCT202003117046797N4; https://irct.ir/trial/46969.

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

In present work, the RP-HPLC method was established for the determination of bromhexine and salbutamol in syrup by using a design of experiment approach. The Plackett-Burman design was applied to screen the influence of independent variables (ratio of organic solvent and pH in mobile phase, flow rate, column temperature, sample injection volume and detection wavelength) on the output data of chromatographic signals (peak area, tailing factor, theoretical plates, resolution) of bromhexine and salbutamol. The Pareto diagram shows that the selected variables affect mainly target function. A central composite design has been used to optimize the values of main factors and Design expert® software predicts the interaction and quadratic model to evaluate the impact of input parameters on output. The optimal conditions were determined with the support of response surface methodology for flow rate 0.9 mL/min, temperature 25 °C and 60% methanol in water with 0.06% orthophosphoric acid as the mobile phase. Good linearity was observed in the concentration range of 8-48 μg/mL for bromhexine and 4-24 μg/mL for salbutamol with a significantly high correlation coefficient (R > 0.999). The limit of detection and limit of quantitation were 0.32 and 0.96 μg/mL, respectively for bromhexine and 0.08 and 0.25 μg/mL, respectively for salbutamol. This method was validated according to ICH guidelines.

Concurrent administration of drugs may alter their pharmacokinetic parameters, so; investigation to what extent bromhexine hydrochloride affects the pharmacokinetic behavior of tilmicosin was our aim of this work. Ten broiler chickens were classified into two groups as follow, the first one (tilmicosin group) was given single oral dose of tilmicosin (20 mg/kg.b.wt.) while the 2nd (pre-treated group) was given single oral dose of bromhexine hydrochloride (1 mg/kg.b.wt.) followed by single oral dose of tilmicosin (20 mg/kg.b.wt.) one hour later. The serum concentration of tilmicosin was measured using High Pressure Liquid Chromatography (HPLC) method. The results revealed that the mean serum concentrations of tilmicosin were significantly lower in pre-treated group when compared with tilmicosin alone group at the corresponding time intervals. Pharmacokinetic parameters were significantly differed (p<0.001) between both groups. The maximum serum concentration were (Cmax0.70±0.02, 0.81±0.04µg/ml), achieved at Tmax of (tmax 0.89±0.16, and 2.10±0.06h), absorption half-life (t0.5ab) of 0.16±0.08, and 0.37±0.01 hour, area under curve (AUC) of 12.96±0.42 and 16.73±0.42µg.h/ml) in tilmicosin-bromhexine and tilmicosin alone groups respectively. In conclusion, based on the obtained pharmacokinetic parameters, these findings showed that bromhexine accelerates the tilmicosin penetration into body tissues, achieving higher and faster concentrations than when given tilmicosin alone.

Recurrent episodes of bronchial obstruction are most common in young children. Various phenotypes of wheezing/bronchial obstruction in preschool children have been described. Large cohort studies demonstrated that it is possible to estimate the risk of chronic bronchopulmonary diseases (developing in adolescence or adulthood) among children with recurrent episodes of bronchial obstruction. All children with recurrent bronchial obstruction should be carefully followed-up and receive timely rational therapy. In children with mild bronchial obstruction, the combination of bromhexine, guaifenesin, and salbutamol in fixed doses has demonstrated high efficacy. Key words: bronchial asthma, bronchial obstruction, children, bromhexine + guaifenesin-salbutamol, prognosis, wheezing phenotypes, COPD

Memoria para optar al título de Químico Farmacéutico
En esta memoria se modificó una pasta de carbono convencional, agregando el líquido iónico 1-butil-3-metilimidazolio hexafluorofosfato a grafito, obteniendo una pasta con proporción 59,2:40,8 (p/p) de grafito y líquido iónico, respectivamente. Utilizando esta superficie como electrodo de trabajo, el fármaco bromhexina presentó una señal anódica en disolución metanol/tampón Britton-Robinson 0,1 M (2,5:97,5 v/v), tanto en voltamperometría cíclica como voltamperometría de pulso diferencial en el intervalo de pH 2-6,5. Esta respuesta fue irreversible y controlada por adsorción de la especie electroactiva. El potencial de pico de oxidación de bromhexina tuvo una dependencia lineal respecto al pH de trabajo, con un punto de inflexión a pH 5, lo cual estaría relacionado con cambios en los equilibrios protonación-deprotonación de la especie electroactiva, con lo cual se estima que el pKa voltamperométrico de la bromhexina es cercano a 5, valor cercano con lo reportado en la literatura. Desde el punto de vista analítico pH 6 fue la condición en la que se obtuvo una mejor reproducibilidad en la señal de corriente, por lo que se seleccionó como pH de trabajo para las medidas voltamperométricas. El electrodo modificado con el líquido iónico se caracterizó empleando mediadores redox clásicos. En el caso del ferrocenometanol se obtuvo un incremento de 4,4 veces en el pico anódico y de 2,7 veces en el pico catódico vs el electrodo sin modificar. Con ferricianuro de potasio se obtuvo un incremento en la respuesta anódica de alrededor de 6 veces debido al efecto del líquido iónico. Por otra parte, al comparar el efecto del líquido iónico en la medición de bromhexina por voltamperometría cíclica vs la pasta sin modificar, se encontró que la señal voltamperométrica se incrementa alrededor de 24,5 veces con el electrodo modificado (Ip = 7,49 μA vs 185,9 μA, respectivamente, una disolución 1×10-4 M). Por otro lado se caracterizó morfológicamente cada uno de estos electrodos por medio de microscopía electrónica de barrido (SEM), en la que se pudo observar que el líquido iónico permite obtener mejor calidad de imágenes, además la pasta mostró una mejor aglutinación y una superficie más homogénea. En las condiciones experimentales seleccionadas (disolución metanol/tampón Britton-Robinson 0,1 M (2,5:97,5 v/v), pH 6), se desarrolló una metodología analítica empleando la técnica de voltamperometría de pulso diferencial. Se obtuvo una respuesta corriente-concentración en un amplio intervalo de concentraciones (6×10-6 - 1×10-4 M), describiéndose dos curvas de calibración, para los intervalos 6×10-6 - 3×10-5M (r2: 0,99888; m: 995943 μA/C intercepto: 0,597 μA) y 1×10-5 - 1×10-4 M (r2: 0,99711; m: 758767 μA/C; intercepto: 7,021 μA). Los límites de detección y cuantificación calculados fueron 1,9×10-6 M y 3,4×10-6 M, respectivamente. La reproducibilidad del método desarrollado exhibió un coeficiente de variación de 5,1 % (en una disolución 5×10-5 M), lo que es un valor aceptable para ser un electrodo modificado. En el ensayo de recuperación; en una matriz compuesta por sacarosa, metilparabeno y ácido cítrico anhidro; se obtuvieron porcentajes similares al valor real: 101 ± 2 % de la cantidad agregada, utilizando la curva de calibración de concentraciones elevadas y 102,3 ± 1,6 % utilizando la curva de concentraciones más bajas. En cuanto a la aplicación del método desarrollado, se cuantificó la cantidad de bromhexina en un jarabe comercial (4 mg/5 mL), y la cantidad encontrada fue 100,9 ± 0,1 % de lo declarado por el fabricante, utilizando la curva de calibración de concentraciones más altas y 100,3 ± 1,1 % utilizando la curva de concentraciones más bajas, además no se requiere un tratamiento previo de la muestra. Utilizando la prueba de t-student se comprobó que el promedio de este método no es significativamente diferente comparado con el promedio de las mediciones del mismo jarabe por HPLC y que cada uno tampoco es significativamente diferente comparados con el valor nominal de 4 mg declarado por el fabricante
Conventional carbon paste was modified by adding 1-butyl-3-methylimidazolium hexafluorophosphate (ionic liquid) at graphite, obtaining a paste with proportion 59.2:40.8 (w/w) of graphite and ionic liquid, respectively. Using this surface as a working electrode, the drug bromhexine had anodic response in methanol/0.1 M Britton-Robinson buffer solution (2.5:97.5 v/v) both by using cyclic voltammetry and by differential pulse voltammetry in the pH range 2-6.5. This response was irreversible and mainly controlled for adsorption of electroactive species. The peak potential had a linear dependence respect on the working pH, with an inflection point at pH 5, which could be related with changes in protonation-deprotonation equilibrium of the electroactive species, whereby an estimated pKa voltammetric of the bromhexine is close to 5, similar value to that reported in the literature. From analytical point view at pH 6 was the condition which better reproducibility in the current signal was obtained, which was selected as working pH. The modified electrode with ionic liquid was characterized using classics redox mediators. In the case of ferrocenemethanol an increase of 4.4 times in the anodic peak and of 2.7 times in the cathodic peak versus unmodified electrode was obtained. With potassium ferricyanide an increase in the anodic response about 6 times due to the effect of the ionic liquid was obtained. On the other hand, to compare the effect of the ionic liquid in the measurement of bromhexine by cyclic voltammetry versus unmodified paste was found that the voltammetric signal was increased about 24.5 times with the modified electrode (ip = 7.49 μA vs 185.9 μA, respectively, 1×10-4 M solution). Each electrode was characterized morphologically by scanning electron microscopy (SEM), in which it was possible to observe that the ionic liquid allows obtain better image quality, in addition the paste showed a better agglutination and most homogeneous surface. In the selected experimental conditions (methanol/0.1 M Britton-Robinson buffer solution (2.5:97.5 v/v), pH 6), an analytical methodology using the differential pulse voltammetry technique was developed. A current-concentration response in a wide concentration range (6×10-6 - 1×10-4 M) was obtained a, describing two calibration curves, in the ranges 6×10-6 - 3×10-5 M (r2: 0.99888, m: 995943 μA/C intercept: 0.597 μA) and 1×10-5 - 1×10-4 M (r2: 0.99, m: 758767 μA/C, intercept: 7.021 μA). The detection and quantification limits calculated were 1.9×10-6 M and 3.4×10-6 M, respectively. The reproducibility of the developed method showed a variation coefficient of 5.1% (5×10-5 M solution), which is an acceptable value for a modified electrode. Regarding the application of the developed method, the amount of bromhexine in syrup 4 mg/5 mL was measured. The amount found was 100.9 ± 0.1 % of the declared for the manufacturer, using the calibration curve of higher concentrations and 100.3 ± 1.1 %, using the curve of lower concentrations. In the recovery test similar percentage were obtained respect to reference value, these being 101 ± 2 % of the amount added, using the calibration curve of higher concentrations and 102.3 ± 1.6 % using the curve of lower concentrations, further pretreatment of the sample is not required. Using the t-student test found that the average of this method is not significantly different compared to the average of the measurements of the same syrup by HPLC and the value is also not significantly different compared to the value of 4 mg declared by manufacturer

Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and medicine been applied to aviculture and pet care. Pigeon racing is one of the sports not well known to the general public. These sportsmen invest a great deal to ensure that their pigeons are disease free. During racing they are exposed to infectious agents in the racing baskets and bring these pathogens back to the racing flock. If you ask any experienced flier what health problem he fears most for his pigeons during the racing season, he will probably say respiratory infection. Respiratory diseases are very common in pigeons. They are the major cause of poor performance and pigeon loss during the racing season. Doxycyline HCI, a broad-spectrum antibiotic, is the world-wide veterinary therapeutic agent of choice for the treatment of Chlamydia, a principle cause of respiratory infection. Doxycyline HCI has several advantages: greater activity, providing effective blood levels for up to 20 hours after a single dose compared to 4 hours for older tetracyclines; causes less disruption to the normal bowel bacteria; has less detrimental effect on the immune system; and is less affected by calcium and other minerals. Bromhexine HCI is an expectorant drug, promoting bronchial secretion and having mucolytic properties. It is commonly used in combination with antibiotics such as doxycycline HCI for the treatment of respiratory infections in the pigeon loft. Because avian medicine has not been commercialised as much as those for human use, it has left fanciers experimenting with dosage forms and strengths resulting in severe consequences. There is a great need for sophisticated medication developed specifically for the pigeon market. Methods: This study investigated the formulation of a direct compressed tablet and a water-soluble powder containing doxycycline HCI and bromhexine HCI respectively and in combination. The formulation and evaluation of the stability of an ophthalmic solution, containing doxycycline HCI was also investigated. Initial test were done on all three formulations. The tablets were inspected visually and tested for uniformity of mass, hardness, friability, disintegration, assay and dissolution. The water-soluble powder was tested for its pH, constitution time, assay, moisture content and visual properties. An "in use" assay was also done on the doxycycline HCI powder. Three containers (stainless steel, glass and plastic) were used and the powder was dissolved in tap water (5 mglml). Samples were taken from every container after 0, 6, 12 and 24 hours and analysed. The results obtained were compared to the same powder but with no citric acid in the formulation. The same containers and time intervals were used for the comparing powder. The ophthalmic solution's appearance, pH, density, viscosity, assay, particulate matter and preservative efficacy were tested. The formulations were stored at three different temperatures and humidities for three months. The above mentioned tests were repeated after every month. An HPLC method for the simultaneous determination of doxycycline HCI and bromhexine HCI was developed and validated. Results and discussion: Based on the different test results generated over the twelve weeks of stability evaluation of the products that were developed in this study, doxycycline HCI and bromhexine HCI, respectively and in combination, seemed to have been relatively stable. The final tablets, water-soluble powders and ophthalmic solution formulations remained stable. The "in use" assay of the powder containing citric acid showed no discoloration, precipitation or breakdown when dissolved in water for a period of 24 hours. The powder lacking the citric acid showed discoloration after only 3 hours. This powder showed significant breakdown as well. The containers used for the storage of the tablets and the powders didn't seal tight enough. The moisture uptake was very high resulting in poor disintegration and dissolution times. Therefore the powder and the tablets should be stored in tightly sealed containers with enough silica as drying agent. The containers used for the tablets, powders and ophthalmic solution respectively, seemed not to influence the stability of the formulations negatively. The newly developed and validated HPLC method was used to analyse the stability samples and it proved to be reliable and easy to execute. Conclusion: Accelerated stability tests indicated that the formulations remained stable and that no significant breakdown occurred. Complete stability trial studies should however be conducted to claim their stability. The newly developed HPLC method was used over the twelve-week period to analyse accelerated stability samples, and it proved to be reliable and easy to carry out.
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.