Sample records for bromhexine
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Bioavailability of bromhexine tablets and preliminary pharmacokinetics in humans.
Bechgaard, E; Nielsen, A
1982-01-01
The absorption of bromhexine from Bromhexin tablets 8 mg, DAK has been compared with that from Bisolvon tablets 8 mg, Boehringer Ingelheim, in a two-way complete crossover study. Four tablets of each of the two bromhexine products, corresponding to a single dose of 32 mg of bromhexine hydrochloride (77.6 mumol), was administered to each of the 10 volunteers. The plasma concentration was followed over the 4-hour period following each administration. By means of Pratt's test for paired data no statistically significant difference (p greater than 0.10) between the two products was found with respect to maximum plasma concentration (89 and 84 nmol.1(-1), respectively), the times for their occurrence (1.3 and 1.0 h, respectively), and the area under the plasma concentration-time curves (140 and 132 nmol.1(-1).h, respectively). It is concluded that Bromhexin, DAK and Bisolvon are bioequivalent. Provisional pharmacokinetic data for bromhexine, after oral administration, in man were obtained. The first-pass effect and the biological half-life were estimated by combining plasma and 30 h urine data from four of the volunteers. The first-pass effect was estimated to be c. 75 per cent, the biological half-life to be c. 6 h, and c. 0.1 per cent of the dose was found as unmetabolized bromhexine in the urine. The data indicate that the pharmacokinetics of bromhexine may be described as a two-compartment open model.
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Biotransformation of bromhexine by Cunninghamella elegans, C. echinulata and C. blakesleeana.
Dube, Aman K; Kumar, Maushmi S
Fungi is a well-known model used to study drug metabolism and its production in in vitro condition. We aim to screen the most efficient strain of Cunninghamella sp. among C. elegans, C. echinulata and C. blakesleeana for bromhexine metabolites production. We characterized the metabolites produced using various analytical tools and compared them with mammalian metabolites in Rat liver microsomes (RLM). The metabolites were collected by two-stage fermentation of bromhexine with different strains of Cunninghamella sp. followed by extraction. Analysis was done by thin layer chromatography, high performance thin layer chromatography, Fourier transform infrared spectroscopy, high performance liquid chromatography and Liquid chromatography-mass spectrometry. The role of Cytochrome P3A4 (CYP3A4) enzymes in bromhexine metabolism was studied. Fungal incubates were spiked with reference standard - clarithromycin to confirm the role of CYP3A4 enzyme in bromhexine metabolism. Three metabolites appeared at 4.7, 5.5 and 6.4min retention time in HPLC. Metabolites produced by C. elegans and RLM were concluded to be similar based on their retention time, peak area and peak response of 30.05%, 21.06%, 1.34%, and 47.66% of three metabolites and bromhexine in HPLC. The role of CYP3A4 enzyme in metabolism of bromhexine and the presence of these enzymes in Cunninghamella species was confirmed due to absence of peaks at 4.7, 5.4 and 6.7min when RLM were incubated with a CYP3A4 enzyme inhibitor - clarithromycin. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.
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Azodi-Deilami, Saman; Abdouss, Majid; Javanbakht, Mehran
2011-05-01
Imprinted polymers are now being increasingly considered for active biomedical uses such as drug delivery. In this work, the use of molecularly imprinted polymers (MIPs) in designing new drug delivery devices was studied. Imprinted polymers were prepared from methacrylic acid (functional monomer), ethylene glycol dimethacrylate (cross-linker), and bromhexine (as a drug template) using bulk polymerization method. The influence of the template/functional monomer proportion and pH on the achievement of MIPs with pore cavities with a high enough affinity for the drug was investigated. The polymeric devices were further characterized by FT-IR, thermogravimetric analysis, scanning electron microscopy, and binding experiments. The imprinted polymers showed a higher affinity for bromhexine and a slower release rate than the non-imprinted polymers. The controlled release of bromhexine from the prepared imprinted polymers was investigated through in vitro dissolution tests by measuring absorbance at λ (max) of 310 nm by HPLC-UV. The dissolution media employed were hydrochloric acid at the pH level of 3.0 and phosphate buffers, at pH levels of 6.0 and 8.0, maintained at 37.0 and 25.0 ± 0.5 °C. Results from the analyses showed the ability of MIP polymers to control the release of bromhexine In all cases The imprinted polymers showed a higher affinity for bromhexine and a slower release rate than the non-imprinted polymers. At the pH level of 3.0 and at the temperature of 25 °C, slower release of bromhexine imprinted polymer occurred.
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Javanbakht, Mehran; Namjumanesh, Mohammad Hadi; Akbari-Adergani, Behrouz
2009-11-15
In this work, a novel method is described for the determination of bromhexine in biological fluids using molecularly imprinted solid-phase extraction as the sample cleanup technique combined with high performance liquid chromatography (HPLC). The water-compatible molecularly imprinted polymers (MIPs) were prepared using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linker, chloroform as porogen and bromhexine as the template molecule. The novel imprinted polymer was used as a solid-phase extraction sorbent for the extraction of bromhexine from human serum and urine. Various parameters affecting the extraction efficiency of the polymer have been evaluated. The optimal conditions for molecularly imprinted solid-phase extraction (MISPE) consisted of conditioning 1 mL methanol and 1 mL of deionized water at neutral pH, loading of 5 mL of the water sample (25 microg L(-1)) at pH 6.0, washing using 2 mL acetonitrile/acetone (1/4, v/v) and elution with 3x 1 mL methanol/acetic acid (10/1, v/v). The MIP selectivity was evaluated by checking several substances with similar molecular structures to that of bromhexine. Results from the HPLC analyses showed that the calibration curve of bromhexine using MIP from human serum and urine is linear in the ranges of 0.5-100 and 1.5-100 microg L(-1) with good precisions (3.3% and 2.8% for 5.0 microg L(-1)), respectively. The recoveries for serum and urine samples were higher than 92%.
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Tantishaiyakul, V; Poeaknapo, C; Sribun, P; Sirisuppanon, K
1998-06-01
A rapid, simple and direct assay procedure based on first-derivative spectrophotometry, using a zero-crossing and peak-to-base measurement at 234 and 324 nm, respectively, has been developed for the specific determination of dextromethorphan HBr and bromhexine HCl in tablets. Calibration graphs were linear with the correlation coefficients of 0.9999 for both analytes. The limit of detections were 0.033 and 0.103 microgram ml-1 for dextromethorphan HBr and bromhexine HCl, respectively. A HPLC method has been developed as the reference method. The results obtained by the first-derivative spectrophotometry were in good agreement with those found by the HPLC method.
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Simultaneous spectrophotometric determination of salbutamol and bromhexine in tablets.
Habib, I H I; Hassouna, M E M; Zaki, G A
2005-03-01
Typical anti-mucolytic drugs called salbutamol hydrochloride and bromhexine sulfate encountered in tablets were determined simultaneously either by using linear regression at zero-crossing wavelengths of the first derivation of UV-spectra or by application of multiple linear partial least squares regression method. The results obtained by the two proposed mathematical methods were compared with those obtained by the HPLC technique.
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Lack of detectable DNA alkylation for bromhexine in man.
Farmer, P B; Parry, A; Franke, H; Schmid, J
1988-09-01
It is known that in vitro incubation of the expectorant drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) with nitrite yields methylcyclohexyl nitrosamine (NMCA). NMCA is capable of methylating DNA when administered to rats. In vivo tests with bromhexine have also demonstrated that the drug methylates DNA when it is orally administered in the presence of sodium nitrite, presumably due to the intragastric formation of NMCA. In this study the potential of bromhexine to methylate nucleic acids in man, under physiological conditions, has been investigated. 20 volunteers were orally administered on each of three successive days 48 mg of bromhexine hydrochloride, labelled with three deuterium atoms in the N-methyl group. Urine was collected before treatment and subsequent to the last dose, and analysed by GC-MS for d0- and d3-7-methylguanine. 7-Methylguanine is naturally occurring in urine owing to the turnover of t-RNA of which it is a minor constituent. It is also a repair product from nucleic acids methylated by carcinogens, which is known to be excreted unmetabolised largely within 24 h of the methylation process. Unlabelled 7-methylguanine was present at levels of 7.36 +/- 2.43 mg/d in control urine and 6.12 +/- 2.36 mg/d in treated urine, in accord with previously published values. The excretion of isotopically labelled 7-methylguanine averaged 0.43 +/- 0.077% of the unlabelled concentration for control urines and 0.44 +/- 0.066% for treated urines, i.e. no d3-7-methylguanine could be detected following the drug treatment. The observed signals were largely accounted for by the naturally occurring isotopes 13C and 15N.(ABSTRACT TRUNCATED AT 250 WORDS)
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Johansson, M; Lenngren, S
1988-11-18
Extraction of the hydrophobic tertiary amine bromhexine from plasma using cyclohexane-heptafluorobutanol (99.5:0.5, v/v) was studied at different pH values. The extraction yield from buffer solutions was quantitative at pH greater than 4.1, but from plasma the extraction yield decreased with increasing pH. Furthermore, at pH 8.4 the extraction yield varied greatly (56-99%) in different human plasma. The addition of lipoproteins to phosphate buffer, at pH 8.1, decreased the extraction yields considerably. Quantitative extraction from plasma was obtained by using a very long extraction time at pH 8.4 or by decreasing the pH to 5.4. The chromatographic system consisted of a reversed-phase column (Nucleosil C18, 5 microns) with an acidic mobile phase (methanol-phosphate buffer, pH 2) containing an aliphatic tertiary amine. UV detection at 308 or 254 nm was used. The limit of quantitation was 5 ng/ml using 3.00 ml of plasma and detection at 254 nm. The intra-assay precision for bromhexine was better than 3.6% at 5 ng/ml.
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Schmid, J; Daneck, K; Koss, F W; Eisenbrand, G; Schlemmer, K H
1988-09-01
Bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammoniumhydr ochloride) forms N-nitroso-N-methyl-N-cyclohexylamine (NMCA) under the conditions of the WHO Nitrosation Assay Procedure (NAP-test). The formation kinetics of this compound was investigated. The formation of NMCA depends on the square of the nitrite concentration. The reaction has a narrow pH-optimum at pH 3. The reaction is quick: After 1 h about 70% of the maximum amount of NMCA is formed. To study this reaction kinetics sensitive assays with a detection limit up to 0.5 ng/ml NMCA were developed. The stability of the components of the system, especially that of NMCA and nitrite, were further studied. The latter is rather instable under conditions found in an acidic stomach.
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Rauha, J P; Salomies, H; Aalto, M
1996-11-01
Liquid chromatographic methods were developed for the determination of bromhexine hydrochloride, methyl p-hydroxybenzoate and propyl p-hydroxybenzoate (method A) and dextromethorphan hydrobromide (method B) in cough-cold syrup formulations. Reversed-phase analytical columns (150 mm x 3.9 mm i.d.) were used with (A) C18 and (B) phenyl as stationary phases and mixtures of (A) acetonitrile and aqueous 15 mM triethylamine solution (43:57) and (B) methanol and aqueous 3% ammonium formate buffer solution (53:47) as mobile phases at a flow rate of 1.0 ml min-1. Both aqueous components were adjusted to pH 3.9. UV detection of analytes was at (A) 245 nm and (B) 278 nm. In both methods, the time required for an HPLC run giving good separations and recoveries was less than 8 min.
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Bazylak, Grzegorz; Nagels, Luc J
2003-08-08
Potentiometric detection of clenbuterol, ambroxol and bromhexine in marketed pharmaceuticals was described in six isocratic HPLC systems. The podant- and macrocyclic-type neutral ionophores, N,N,N',N'-tetracyclohexyl-oxybis(o-phenyleneoxy)diacetamide (TOPA) and hexakis(2,3,6-tri-O-octyl)-alpha-cyclodextrin (OCD), were applied in poly(vinyl)chloride (PVC)-based liquid membrane electrodes. Both types of neutral ionophores improve the sensitivity for all mentioned drugs when compared with a tetrakis(p-chlorophenyl)borate (BOR)-based electrode as well as with single wavelength UV detection. Detection limits (S/N=3) of 2.6 x 10(-10) mol l(-1) (injected concentration) for the highly hydrophobic bromhexine were achieved with the TOPA-based electrode and a cyano reversed-phase (RP)-HPLC with Uptisphere UP5CN-25QS silica column (250 x 4.6 mm i.d.) eluted with acetonitrile (AcN)-ethanol-perchloric acid (1.66 mM) (60:2:38, v/v/v) (pH* 2.45). Comparable result was obtained with OCD-based electrodes and an XTerra RP18 hybrid silica-polymer column eluted with AcN-phosphoric acid (20 mM) (25:75, v/v) (pH* 2.60). In the mobile phases containing 60-75% v/v AcN or methanol, stable and reproducible response of both types of neutral ionophore-based electrodes was observed for at least 3 days. The results of the validated procedure for reliable simultaneous determination of the drugs in fortified representative samples of pharmaceuticals were also presented.
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Kaneko, Kenitiro; Ono, Yasuyuki; Tainaka, Takahisa; Sumida, Wataru; Ando, Hisami
2009-07-01
Symptoms of choledochal cysts are caused by protein plugs made of lithostathine, which block the long common channel and increase pancreaticobiliary ductal pressure. Agents that dissolve protein plugs can provide relief from or prevent symptoms. In the present study, drugs reportedly effective for pancreatic and biliary stones were used in dissolution tests. Protein plugs were obtained from choledochal cysts during surgery in two children (5- and 6-year-old girls). Plugs approximately 2 mm in diameter were immersed in citric acid, tartaric acid, dimethadione, bromhexine, dehydrocholic acid, sodium citrate, hydrochloric acid, and sodium hydroxide solutions under observation with a digital microscope. The pH of each solution was measured using a pH meter. Plugs dissolved in citric acid (5.2 mM; pH 2.64), tartaric acid (6.7 mM; pH 2.51), dimethadione (75 mM; pH 3.70), hydrochloric acid (0.5 mM; pH 3.13), and sodium hydroxide (75 mM; pH 12.75) solutions. Plugs did not dissolve in dimethadione (7.5 mM; pH 4.31), bromhexine (0.1%; pH 4.68), dehydrocholic acid (5%; pH 7.45), and sodium citrate (75 mM; pH 7.23) solutions. Protein plugs in choledochal cysts are dissolved in acidic and basic solutions, which may eliminate longitudinal electrostatic interactions of the lithostathine protofibrils.
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NASA Astrophysics Data System (ADS)
Abdel-Ghani, N. T.; Rizk, M. S.; Mostafa, M.
2013-07-01
Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL-1, using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ⩾0.995 (n = 6) with a relative standard deviation (RSD) ⩽1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully.
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Current Usage of Medication in NATO Aircrew Medication Database
2001-06-01
beclometasone u u u u u* u ** u bromhexine u u u u u u **u u budesonide u u u u u ** u carbocysteine u u u u u ** u clobutinol u ** cromoglicicacid...u u budesonide u u u* u u u u u u cetirizine u u* f f u f u f u* cromoglycicacid u u u u I u u u u u u fexofenadine f u u flunisolide u u u u u U
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Abdel-Ghani, N T; Rizk, M S; Mostafa, M
2013-07-01
Simple, rapid, sensitive, precise and accurate spectrophotometeric methods for the determination of ephedrine hydrochloride (E-HCl) and bromhexine hydrochloride (Br-HCl) in bulk samples, dosage form and in spiked urine samples were investigated. The methods are based on the formation of a yellow colored ion-associates due to the interaction between the examined drugs with picric acid (PA), chlorophyllin coppered trisodium salt (CLPH), alizarin red (AR) and ammonium reineckate (Rk) reagents. A buffer solution had been used and the extraction was carried out using organic solvent, the ion associates exhibit absorption maxima at 410, 410, 430 and 530 nm of (Br-HCl)with PA, CLPH, AR and Rk respectively; 410, 410, 435 and 530 of (E-HCl) with PA, CLPH, AR and Rk respectively. (E-HCl) and (Br-HCl) could be determined up to 13, 121, 120 and 160; 25, 200, 92 and 206 μg mL(-1), using PA, CLPH, AR and Rk respectively. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity, Sandell sensitivity were determined for the investigated drug. The correlation coefficient was ≥0.995 (n=6) with a relative standard deviation (RSD) ≤1.15 for five selected concentrations of the reagents. Therefore the concentration of Br-HCl and E-HCl drugs in their pharmaceutical formulations and spiked urine samples had been determined successfully. Copyright © 2013 Elsevier B.V. All rights reserved.
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In vitro effects of ambroxol on Cryptococcus adherence, planktonic cells, and biofilms.
Kong, Qingtao; Du, Xue; Huang, Suyang; Yang, Rui; Zhang, Chengzhen; Shen, Yongnian; Liu, Weida; Sang, Hong
2017-07-01
The antifungal effects of ambroxol (Amb; the metabolite VIII of bromhexine) against Cryptococcus planktonic cells and mature biofilms were investigated in this study. Amb showed antifungal activity against planktonic cells and mature biofilms. Disk diffusion test similarly showed antifungal profile for planktonic cells. Furthermore, Amb was found to be synergetic with fluconazole against planktonic cells and reduced the adherence of cells to polystyrene. Our results suggest that Amb can inhibit cryptococcal cells and biofilms, indicating its potential role in the prevention and treatment of cryptococcosis. © 2017 APMIS. Published by John Wiley & Sons Ltd.
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Porel, A.; Haty, Sanjukta; Kundu, A.
2011-01-01
The aim of the present study was the development and subsequent validation of a simple, precise and stability-indicating reversed phase HPLC method for the simultaneous determination of guaifenesin, terbutaline sulphate and bromhexine hydrochloride in the presence of their potential impurities in a single run. The photolytic as well as hydrolytic impurities were detected as 3,5-dihydroxybenzoic acid, 3,5-dihydroxybenzaldehyde, 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl) amino]-ethanone from terbutaline, 2-methoxyphenol and an unknown impurity identified as (2RS)-3-(2-hydroxyphenoxy)-propane-1,2-diol from guaifenesin. The chromatographic separation of all the three active components and their impurities was achieved on Wakosil II column, using phosphate buffer (pH 3.0) and acetonitrile as mobile phase which was delivered initially in the ratio of 80:20 (v/v) for 18 min, then changed to 60:40 (v/v) for next 12 min, and finally equilibrated back to 80:20 (v/v) for 10 min. Other HPLC parameters were: Flow rate at 1.0 ml/min, detection wavelengths 248 and 280 nm, injection volume 10 μl. The calibration graphs plotted with five concentrations of each component were linear with a regression coefficient R2 >0.9999. The limit of detection and limit of quantitation were estimated for all the five impurities. The established method was then validated for linearity, precision, accuracy, and specificity and demonstrated to be applicable to the determination of the active ingredients in commercial and model cough syrup. No interference from the formulation excipients was observed. These results suggest that this LC method can be used for the determination of multiple active ingredients and their impurities in a cough and cold syrup. PMID:22131621
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Porel, A; Haty, Sanjukta; Kundu, A
2011-01-01
The aim of the present study was the development and subsequent validation of a simple, precise and stability-indicating reversed phase HPLC method for the simultaneous determination of guaifenesin, terbutaline sulphate and bromhexine hydrochloride in the presence of their potential impurities in a single run. The photolytic as well as hydrolytic impurities were detected as 3,5-dihydroxybenzoic acid, 3,5-dihydroxybenzaldehyde, 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl) amino]-ethanone from terbutaline, 2-methoxyphenol and an unknown impurity identified as (2RS)-3-(2-hydroxyphenoxy)-propane-1,2-diol from guaifenesin. The chromatographic separation of all the three active components and their impurities was achieved on Wakosil II column, using phosphate buffer (pH 3.0) and acetonitrile as mobile phase which was delivered initially in the ratio of 80:20 (v/v) for 18 min, then changed to 60:40 (v/v) for next 12 min, and finally equilibrated back to 80:20 (v/v) for 10 min. Other HPLC parameters were: Flow rate at 1.0 ml/min, detection wavelengths 248 and 280 nm, injection volume 10 μl. The calibration graphs plotted with five concentrations of each component were linear with a regression coefficient R(2) >0.9999. The limit of detection and limit of quantitation were estimated for all the five impurities. The established method was then validated for linearity, precision, accuracy, and specificity and demonstrated to be applicable to the determination of the active ingredients in commercial and model cough syrup. No interference from the formulation excipients was observed. These results suggest that this LC method can be used for the determination of multiple active ingredients and their impurities in a cough and cold syrup.
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Gause, A
2007-02-01
For the treatment of sicca symptoms as a manifestation of Sjögren's syndrome there are various tear substitutes as well as artificial saliva. The appropriate substances are discussed in this article. In addition to reducing symptoms, some of the effective compounds offer the advantage of infection prophylaxis in the form of better lubrication of the mucous membranes in the airways as well as reduced susceptibility to candidiasis. The presence of bromhexin in the catalogue of the statutory medical insurance agencies is recommended. Certain of the available drugs are still only available in foreign pharmacies.
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Contaminations of herbal products determined by NMR fingerprint.
Nicoletti, Marcello; Petitto, Valentina
2010-09-01
The utilisation of NMR fingerprinting is proposed as a rapid, available and reliable method to determine the contamination of herbal products. The presence of nimesulide has been reported recently as the contaminant of P.C. 28 Plus, a product based on herbal drugs marketed by the Italian company Cosval. The presence of the substance, as well as its relevant concentration (5%), was first reported by HPLC/MS analysis by other authors. The use of an NMR fingerprint confirmed the previous contamination with nimesulide in P.C. 28 Plus. The same contaminant was also found in P.C. 28 Pink. Furthermore, an analysis of Alergix Plus, another product of the same factory, evidenced the presence of bromhexin.
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Lacrimal secretion stimulants: sigma receptors and drug implications.
Shirolkar, S; Schoenwald, R D; Barfknecht, C F; Xia, E; Cheng, B; Iwai, Y; Ignace, C C; Vidvauns, S; Newton, R E
1993-01-01
3H-DTG (1.3-di(2-[5-3H]tolyl)guanidine) or 3H-haloperidol was added to sigma-receptors (25 nM) in the presence of 25 nM spiperone and incubated with increasing concentrations of bromhexine derivatives (phenylalkylamines; 10(-9) to 10(-2)M) in membrane homogenate suspensions. IC50 values for two derivatives ranged from 3.2 to 8.8 nM for both radioligands. A preferred derivative, 7A (N,N'-dimethyl-2-phenyl-ethylamine), yielded an IC50 of 7.8 nM for 3H-haloperidol but showed much less affinity in displacing 3H-DTG (IC50 = 900 nM). Applying the technic of Bromberg [Exp. Eye Res., 40:313-320, 1985], in vitro protein secretion rates were measured following stimulation of either lacrimal gland slices or isolated, intact lacrimocytes with the compounds. In vitro protein secretion rates exhibit a dose-response relationship with increases in protein release up to a concentration of 10(-8) to 10(-4) M for various derivatives of bromhexine and 10(-4) M for carbachol. By means of Schirmer strips, tear fluid was collected over a five minute period at 10 and 60 minutes post-dosing following the topical application (50 microliters) to the right eye of New Zealand white rabbits (n = 20-24) of 7A at various concentrations. Incubation of lacrimocytes with 7A alone (10(-4) M), with haloperidol (10(-4) M) alone or in combination show that 7A is acting as an agonist to stimulate protein release, whereas haloperidol is acting as an antagonist to inhibit release. In vivo protein secretion rates also show a dose-response curve (at both 10 and 60 minutes post-dosing) for 7A that reach a statistically significant maximum in the dosed eye at a concentration of 0.15% w/v. Analysis of protein extracts using size exclusion HPLC shows an increase in secretory proteins, particularly tear-specific prealbumin.
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Hamidi-Asl, Ezat; Daems, Devin; De Wael, Karolien; Van Camp, Guy; Nagels, Luc J
2014-12-16
In the present paper, the utility of a special potentiometric titration approach for recognition and calculation of biomolecule/small-molecule interactions is reported. This approach is fast, sensitive, reproducible, and inexpensive in comparison to the other methods for the determination of the association constant values (Ka) and the interaction energies (ΔG). The potentiometric titration measurement is based on the use of a classical polymeric membrane indicator electrode in a solution of the small-molecule ligand. The biomolecule is used as a titrant. The potential is measured versus a reference electrode and transformed into a concentration-related signal over the entire concentration interval, also at low concentrations, where the millivolt (y-axis) versus log canalyte (x-axis) potentiometric calibration curve is not linear. In the procedure, Ka is calculated for the interaction of cocaine with a cocaine binding aptamer and with an anticocaine antibody. To study the selectivity and cross-reactivity, other oligonucleotides and aptamers are tested, as well as other small ligand molecules such as tetrakis(4-chlorophenyl)borate, metergoline, lidocaine, and bromhexine. The calculated Ka compared favorably to the value reported in the literature using surface plasmon resonance. The potentiometric titration approach called "concentration-related response potentiometry" is used to study molecular interaction for seven macromolecular target molecules and four small-molecule ligands.
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Rainville, Paul D; Simeone, Jennifer L; Root, Dan S; Mallet, Claude R; Wilson, Ian D; Plumb, Robert S
2015-03-21
The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data quality, reduce animal usage, and save costs in safety assessment studies. The analysis of these samples presents new challenges for bioanalytical scientists, both in terms of sample processing and analytical sensitivity. The use of two dimensional LC/MS with, at-column-dilution for the direct analysis of highly organic extracts prepared from biological fluids such as dried blood spots and plasma is demonstrated. This technique negated the need to dry down and reconstitute, or dilute samples with water/aqueous buffer solutions, prior to injection onto a reversed-phase LC system. A mixture of model drugs, including bromhexine, triprolidine, enrofloxacin, and procaine were used to test the feasibility of the method. Finally an LC/MS assay for the probe pharmaceutical rosuvastatin was developed from dried blood spots and protein-precipitated plasma. The assays showed acceptable recovery, accuracy and precision according to US FDA guidelines. The resulting analytical method showed an increase in assay sensitivity of up to forty fold as compared to conventional methods by maximizing the amount loaded onto the system and the MS response for the probe pharmaceutical rosuvastatin from small volume samples.
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Noguchi, Shuji; Kajihara, Ryusuke; Iwao, Yasunori; Fujinami, Yukari; Suzuki, Yoshio; Terada, Yasuko; Uesugi, Kentaro; Miura, Keiko; Itai, Shigeru
2013-03-10
Computed tomography (CT) using synchrotron X-ray radiation was evaluated as a non-destructive structural analysis method for fine granules. Two kinds of granules have been investigated: a bromhexine hydrochloride (BHX)-layered Celphere CP-102 granule coated with pH-sensitive polymer Kollicoat Smartseal 30-D, and a wax-matrix granule constructed from acetaminophen (APAP), dibasic calcium phosphate dehydrate, and aminoalkyl methacrylate copolymer E (AMCE) manufactured by melt granulation. The diameters of both granules were 200-300 μm. CT analysis of CP-102 granule could visualize the laminar structures of BHX and Kollicoat layers, and also visualize the high talc-content regions in the Kollicoat layer that could not be detected by scanning electron microscopy. Moreover, CT analysis using X-ray energies above the absorption edge of Br specifically enhanced the contrast in the BHX layer. As for granules manufactured by melt granulation, CT analysis revealed that they had a small inner void space due to a uniform distribution of APAP and other excipients. The distribution of AMCE revealed by CT analysis was also found to involve in the differences of drug dissolution from the granules as described previously. These observations demonstrate that CT analysis using synchrotron X-ray radiation is a powerful method for the detailed internal structure analysis of fine granules. Copyright © 2013 Elsevier B.V. All rights reserved.
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El-Gindy, Alaa; Emara, Samy; Shaaban, Heba
2007-02-19
Three methods are developed for the determination of two multicomponent mixtures containing guaiphenesine (GU) with salbutamol sulfate (SL), methylparaben (MP) and propylparaben (PP) [mixture 1]; and acephylline piperazine (AC) with bromhexine hydrochloride (BX), methylparaben (MP) and propylparaben (PP) [mixture 2]. The resolution of the two multicomponent mixtures has been accomplished by using numerical spectrophotometric methods such as partial least squares (PLS-1) and principal component regression (PCR) applied to UV absorption spectra of the two mixtures. In addition HPLC method was developed using a RP 18 column at ambient temperature with mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 4.3 (60:40, v/v), with UV detection at 243 nm for mixture 1, and mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 3 (50:50, v/v), with UV detection at 245 nm for mixture 2. The methods were validated in terms of accuracy, specificity, precision and linearity in the range of 20-60 microg ml(-1) for GU, 1-3 microg ml(-1) for SL, 20-80 microg ml(-1) for AC, 0.2-1.8 microgml(-1) for PP and 1-5 microg ml(-1) for BX and MP. The proposed methods were successfully applied for the determination of the two multicomponent combinations in laboratory prepared mixtures and commercial syrups.
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Management of acute cough by Zataria multiflora Boiss as an alternative treatment.
Mahboubi, Mohaddese
2018-01-01
Cough, as a defensive reflux mechanism, removes foreign objects and secretions from bronchi and bronchioles of airways. Zataria multiflora is a popular plant for treatment of cough in Iranian traditional medicine. The aim of this review was to evaluate the potency of Z. multiflora as an alternative treatment in management of acute cough and its possible mechanisms of action. Here the authors compiled information about Z. multiflora in the treatment of cough from all accessible resources and books. The results of this investigation showed that there were five clinical studies that evaluated the efficacy of Z. multiflora essential oil or extract alone (n = 1), in combination with Althaea officinalis (n = 2) or Foeniculum vulgare essential oil (n = 1), in the form of syrup (n = 3), oral drop (n = 1) and soft capsule (n = 1), for the treatment of acute cough in comparison with placebo or synthetic drugs (bromhexine, dextromethorphan and clobutinol). All clinical studies confirmed the efficacy of Z. multiflora in the amelioration of acute cough in pediatric (n = 1) and adult patients (n = 4) without any adverse effects. Different mechanisms, such as anti-inflammatory, analgesic, antimicrobial, relaxant and immune-enhancement, may be responsible for the efficacy of Z. multiflora in cough relief. Other clinical trials can be performed with Z. multiflora in combination with ivy leaf extract or primrose root extract on patients with cough. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.
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Okamoto, Hitoshi; Nakajima, Toshiaki; Ito, Yuji; Aketo, Takao; Shimada, Kenji; Yamato, Susumu
2005-03-09
Cyclodextrin-modified microemulsion electrokinetic chromatography (CD-MEEKC) was used to simultaneously determine 14 active ingredients (thiamine nitrate, anhydrous caffeine, acetaminophen, riboflavin, guaifenesin, pseudoephedrine hydrochloride, ascorbic acid, ethenzamide, DL-methylephedrine hydrochloride, dihydrocodeine phosphate, ibuprofen, noscapine, carbinoxamine maleate, and bromhexine hydrochloride) in a cold medicine. Separation of the ingredients was optimized by changing the SDS concentration and oil type and the addition of 2-propanol and cyclodextrin (CD) to the separation solution. The separation selectivity was improved dramatically by changing CD type. All of the active ingredients and formulation excipients were successfully separated with the use of a separation solution consisting of 0.81% (w/w) pentane, 6.61% (w/w) 1-butanol, 2% (w/w) 2-propanol, 4.47% (w/w) SDS, and 86.11% (w/w) 10 mM sodium tetraborate solution with 3 mM 2,6-di-O-methyl-beta-CD. The established method was then validated and demonstrated to be applicable to the determination of the active ingredients in a model cold medicine. No interference from the formulation excipients was observed. Good linearities were obtained with correlation coefficients above 0.999. Recovery and precision ranged from 99.1 to 100.7% and from 0.5 to 2.8% R.S.D., respectively. The detection limit for ingredients ranged from 0.6 to 4.2 microg ml(-1). Good agreement was obtained between the established method and the traditional HPLC method. These results suggest that CD-MEEKC can be used for the determination of multiple ingredients in cold medicine.
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Brochmann, Rikke Prejh; Helmfrid, Alexandra; Jana, Bimal; Magnowska, Zofia; Guardabassi, Luca
2016-06-24
New therapeutic strategies are needed to face the rapid spread of multidrug-resistant staphylococci in veterinary medicine. The objective of this study was to identify synergies between antimicrobial and non-antimicrobial drugs commonly used in companion animals as a possible strategy to restore antimicrobial susceptibility in methicillin-resistant Staphylococcus pseudintermedius (MRSP). A total of 216 antimicrobial/non-antimicrobial drug combinations were screened by disk diffusion using a clinical MRSP sequence type (ST) 71 strain resistant to all six antimicrobials tested (ampicillin, ciprofloxacin, clindamycin, doxycycline, oxacillin and trimethoprim/sulfamethoxazole). The most promising drug combination (doxycycline-carprofen) was further assessed by checkerboard testing extended to four additional MRSP strains belonging to ST71 or ST68, and by growth inhibition experiments. Seven non-antimicrobial drugs (bromhexine, acepromazine, amitriptyline, clomipramine, carprofen, fluoxetine and ketoconazole) displayed minimum inhibitory concentrations (MICs) ranging between 32 and >4096 mg/L, and enhanced antimicrobial activity of one or more antimicrobials. Secondary screening by checkerboard assay revealed a synergistic antimicrobial effect between carprofen and doxycycline, with the sum of the fractional inhibitory concentration indexes (ΣFICI) ranging between 0.3 and 0.5 depending on drug concentration. Checkerboard testing of multiple MRSP strains revealed a clear association between synergy and carriage of tetK, which is a typical feature of MRSP ST71. An increased growth inhibition was observed when MRSP ST71 cells in exponential phase were exposed to 0.5/32 mg/L of doxycycline/carprofen compared to individual drug exposure. Carprofen restores in vitro susceptibility to doxycycline in S. pseudintermedius strains carrying tetK such as MRSP ST71. Further research is warranted to elucidate the molecular mechanism behind the identified synergy and its linkage to tetK.
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Zhang, Yunhui; Fu, Yakun; Yu, Jialin; Ai, Qing; Li, Junshuai; Peng, Ningning; Song, Sijie; He, Yu; Wang, Zhengli
2015-11-01
Central venous catheters are widely used in neonatal intensive care units (NICUs) nowadays. The commonest cause of catheter-related bloodstream infections (CRBSIs) is coagulase-negative staphylococci (CoNS). Ambroxol, an active metabolite of bromhexine, exhibits antimicrobial activity against strains producing biofilm and enhances the bactericidal effect of some antibiotic by breaking the structure of biofilm. In this study, we aimed to determine the effect of ambroxol with vancomycin on the biofilm of Staphylococcus epidermidis (S. epidermidis) in vitro and in vivo. In the in vitro study, the biofilm of S. epidermidis was assessed by XTT reduction assay and analysed by confocal laser scanning microscopy (CLSM). In the in vivo study, a rabbit model of CRBSIs was created by intravenous intubation with a tube covered with S. epidermidis biofilm. The rabbits received one of the following four treatments by means of antibiotic lock therapy: normal heparin, ambroxol, vancomycin, or vancomycin plus ambroxol each for 3 days. The microstructure of the biofilm was assessed by scanning electron microscopy (SEM). The number of bacterial colonies in the organs (liver, heart, and kidney) and on the intravenous tubes was measured on agar plates. Pathological changes in the organs (liver, heart, and kidney) were observed with Hematoxylin-Eosin staining. The ambroxol exhibits significant efficacy to potentiate the bactericidal effect of vancomycin on S. epidermidis biofilm both in vitro and in vivo. The antibiotic lock therapy using a combination of ambroxol and vancomycin reveals a high ability to eradicate S. epidermidis biofilms in vivo. These results provide the basis of a useful anti-infection strategy for the treatment of CRBSIs. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.