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Natural molecules have been a boon in the field of medical science and therapeutics. With the progress of latest technology and advancement in synthetic chemistry and computational biology, it has now become possible to precisely decide the best possible fit inhibitor molecule for the pathologically important target molecules in the human body. In recent history, many naturally occurring molecules have been derivatized to improve the inhibitory potential. Bromhexine is one such molecule that has been derivatized from the naturally occurring molecule vasicine. Vasicine is obtained from Adhatodavasica, a very well known herb for respiratory and other inflammatory diseases. The present review describes the importance and uses of bromhexine in the area of therapeutics with a light on its mechanism of action and its use in several diseases such as asthma and chronic bronchitis.
Chronic Bronchitis
Natural molecules have been a boon in the field of medical science and therapeutics. With the
progress of latest technology and advancement in synthetic chemistry and computational
biology, it has now become possible to precisely decide the best possible fit inhibitor molecule
for the pathologically important target molecules in the human body. In recent history, many
naturally occurring molecules have been derivatized to improve the inhibitory potential.
Bromhexine is one such molecule that has been derivatized from the naturally occurring
molecule vasicine. Vasicine is obtained from Adhatodavasica, a very well known herb for
respiratory and other inflammatory diseases. The present review describes the importance
and uses of bromhexine in the area of therapeutics with a light on its mechanism of action and
its use in several diseases such as asthma and chronic bronchitis.
Bromhexine, a benzylamine derived cardiac depressant of
vasicine, is a quinazoline alkaloid obtained from the plant
Adhatoda vasica. It was developed in the research laboratory of
Boehringer Ingelheim in the late 1950s as an active ingredient for
pharmaceutical use. It was introduced in 1963 under the
trademark of Bisolvon® and is chemically known as N-
cyclohexly-N-methyl-(2-amino-3, 5-dibromobenzyl) ammonium
chloride. [1] The chemical structure of bromhexine is represented
in figure 1.
It is also known by the synonym as Bromhexine Hydrochloride.
Bromhexine is majorly used as a mucolytic agent for curing
respiratory disorders correlated with excessive or viscid mucus. It is
used as a secretolytic expectorant for the effective treatment of
cough with phlegm. [2, 3] In addition, bromhexine also has
antioxidant properties. It is mainly associated with upper as well as
lower respiratory tract infections [4] such as broncho-pneumonia
[5], bronchiectasis [6], acute and chronic bronchitis [7], sinusitis [8],
mixed respiratory conditions [9] & diseases like allergic asthma [10]
and obstructive airway diseases whose course is complicated by
infections. [11] This compound is accepted well as it has a low level
of toxicity. [12] It is generally well tolerated and can also be given to
children of different ages.
Bromhexine exists as a white crystalline powder in solid state
and is insoluble in water but shows little solubility in alcohol. It is
also slightly soluble in chloroform and methylene chloride. [13]
Bromhexine's intentional use is to support the body's activities
associated for clearing mucus from the respiratory tract. The
mechanism of action is based on phlegm degradation, thereby easing
coughs. [3] It helps in enhancing the production of serous mucus in
the respiratory tract and helps in the production of thinner and less
viscous phlegm. This produces a secretomotoric effect by helping the
cilia in expectoring the phlegm out of the lungs. Due to this reason, it
is often regarded as an important component of cough syrups. [14]
Bromhexine begins to act on the mucus at the formative stages in
the glands inside the mucus-secreting cells. [12] Through oral
administration in patients, the onset of action of bromhexine begins
Int J Biol Med Res.2018;9(3):6455-6459
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Int J Biol Med Res
Volume 6, Issue 2, April 2015
Copyright 2010 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685. All rights reserved.
* Corresponding Author : Dr.Rachana
Copyright 2011. CurrentSciDirect Publications. IJBMR - All rights reserved.
Associate Professor, Department of Biotechnology,
Jaypee Institute of Information Technology,
A-10, Sector 62, Gautam Buddha Nagar, Noida, 201309,
Uttar Pradesh, India
Phone: +91 9315434437
Email ID:
a b
Ayushi Bhagat , and Rachana *
M.Tech Student, Department of Biotechnology, Jaypee Institute of Information Technology, Noida
b*Associate Professor, Department of Biotechnology, Jaypee Institute of Information Technology, Noida
Jaypee Institute of Information Technology,
A10, Sector 62, Gautam Buddha Nagar, Noida, 201309, Uttar Pradesh, India
after 30 minutes. Its complete effect is visualized by an increased
production of respiratory tract fluid after 2-3 days of the
commencement of treatment. Following oral administration,
bromhexine has been shown to increase the volume of sputum
and to decrease the viscosity of bronchial secretions in chronic
bronchitis patients. [15-17] The drug induces the hydrolytic
depolymerization of mucous protein fibers of high molecular
weight and stimulates the activity of the ciliated epithelium. [18-
19] It has been shown to reduce the viscosity of bronchial
secretions in both animals [2] and men. [20]
Anon in 1971 postulated an increase in the lysosomal activity
which was associated with bromhexine. [15] There were
significant improvements in the pulmonary function besides an
ease in expectoration, in bronchitis patients. Several other
pharmacological effects of bromhexine have also been posited
such as an increment of secretion from exocrine glands (eg, tear
production) and an upsurge in pulmonary surfactant production.
[17-18] Bromhexine also has clinical efficacy to increase sputum
concentrations in combination with various antibiotics such as
oxytetracycline, erythromycin, ampicillin and amoxicillin. [13, 16,
17, 21] However, some of these effects reported (exocrine
stimulation and increased sputum concentrations etc.) have not
yet been confirmed in the studies. [22-24]
It has been suggested that, Ambroxol (NA-872) which is a
metabolite of bromhexine, can also contribute to an increased
sec reti on f rom e xoc ri ne g land s dur in g b romh exin e
administration. [25-26] Asthmatic and chronic bronchitis
patients have sputum comprising of fibre systems characterized
with mucoproteins and mucopolysaccharides. The nuclei of cells
lining the mucosal wall of the bronchial track disintegrate leading
to the formation of purulent fibres of deoxyribonucleic acid. This
leads to the formation of sputum viscosity due to an increase in
the mucopolysaccharide and DNA fibre systems. Although,
antibiotics effectively decrease the DNA contribution, it has been
seen under the microscope that bromhexine helps in breaking
down the mucopolysaccharide fragments and thus cause a
reduction in sputum viscosity. Therefore, it is now more easily
removed through coughing. Bromhexine therapy often amends
the sputum immunoglobulins and causes changes in the secretory
granules of bronchial and nasal mucosa glands as seen through
electron microscopic studies. [1] Although there is a decline in the
sputum volume, its viscosity remains low until the bromhexine
treatment is maintained. This causes an increased response to
bronchodilator drugs by our body. It is preferable in some cough
medication as it does not include any sedatives which can
otherwise make the users feel drowsy. [27]
Various studies have been performed to analyse the
therapeutic applications for bromhexine for Asthma. Forty seven
patients, who were experiencing symptoms of respiratory disease
such as, the production of mucopurulent sputum were given a
dosage of 8 mg of bromhexine thrice daily for one week in a double
blind controlled crossover clinical study. An increase in the
ventilatory capacity leading to significant clinical improvement
was seen in a greater number of patients than those who were
administered placebo. However, there was a difference in the
results in different parts of the trial which was carried out in
winters and summers. [28] On the other hand, in another double
blind crossover technique, thirty four patients were given the oral
treatment with two drugs and placebo for three consecutive times
with a gap of 12 days. These people suffered from chronic asthma
and persistent mucoid expectoration. There was no significant
enhancement in the sputum viscosity, clinical state, PEF or airway
resistance. Th ough, patients' ow n preference regardi ng
bromhexine as a mucolytic agent increased by 0.1%. [29]
Similarly in another study of a double blind therapeutic
regimen, fourteen patients received oral or intravenous treatment
of bromhexine or placebo in conjunction with the regular
standard therapy for acute severe asthma. There was no
prominent recovery seen for bromhexine group of patients. [30]
In the next decade, twenty children in the range of ages from 3 to
14 years were nebulized with 2 ml of saline or bromhexine (2
mg/ml) for two weeks. They had been suffering from bronchial
asthma in combination with chronic sinusitis. Both treatments
had shown compelling improvements but saline nebulization was
more significant than bromhexine. [31] Hence, it can be seen that
although there are several studies related to asthma that have
been performed with bromhexine, some have shown positive
effects while the others have shown nil effect.
Similar to asthma, in the case of chronic bronchitis, either
types of reports were available in which positive or none effects
were seen. Bromhexine has been shown to change the sputum
characteristics in vitro but, it has produced varying results in
several clinical trials. [32] Here is a brief scenario highlighting
both the positive and nil effects observed by the bromhexine
therapy in chronic bronchitis patients.
4.2.1 Positive effects of bromhexine for chronic bronchitis
Hamilton et al. reported that, when 16 mg bromhexine was
administered orally for three times daily for 11 days in twenty five
patients in a double blind clinical trial, it resulted in a prominent
increment in sputum volume along with a reduction in the
viscosity of sputum. No change in the ventilatory capacity or in the
respiratory state of the patients was visualized. There was a
change in the yield values with no possible side effects seen
amongst patients. [20] In agreement to Hamilton, Seventy-five
patients diagnosed with chronic bronchitis were administered a
daily dosage of 24 mg bromhexine and a placebo. Sixty one
patients produced suitable results for evaluation. Out of these, a
significant group felt better after consumption of bromhexine and
showed fewer side effects as compared to the placebo group. [33]
It has been seen that intra-alveolar haemorrhage and
sustained intermittent positive pressure ventilation therapy
leads to an increase in the viscosity of bronchial secretions in
chest injuries. To stop this kind of injuries an appropriate
mucolytic drug can be used to break the mucopolysaccharide
complex along with the moistening of inhaled air. When
bromhexine was used 12 mg daily along with ventilation therapy
in a patient with chronic bronchitis, it showed significant results.
[14] In yet another controlled double blind cross over clinical
study of twenty one patients suffering from severe chronic
bronchitis, 24 mg or 48 mg bromhexine was significantly
correlated with a placebo for 14 weeks daily. Sodium fluorescein
was utilized as a drug marker. Sufficient data was obtained from
eighteen patients with no change or enhancement in the
ventilatory capacity or sputum properties. No side effects were
Ayushi Bhagat & Rachana/Int J Biol Med Res.9(3):6455-6459
bronchitis exacerbations and those having mucoid sputum for
14 days. There was no change in the volume, yield value and
viscosity of the sputum. The ventilatory capacity of the lungs
remained unaffected after treatment with no shift in the ease of
breathing. [41] In another study, eleven out of twenty two patients
were asked to take bromhexine along with 1 g of erythromycin
ethyl succinate twice daily for a period of 10 days. The other half
group were administered with placebo along with the antibiotic.
These people had acute exacerbations of chronic bronchitis.
There was no clinical improvement seen in both these groups.
[42] .
Bromhexine has also been tested for the treatment of
nephropathy. Male wistar rats were given single intravenous
injections of streptozotocin (40 mg/kg) for the onset of diabetes.
They were treated with bromhexine at two different dose levels
for the subsequent 13 months. Renal analysis of these rats along
with non diabetic controls and untreated diabetic rats showed a
prominent increase in the glomerular volume. It led to an increase
in the thickness of the basement membrane in untreated diabetic
animals. Diabetic rats treated with bromhexine showed a
reduction in the glomerular volume as compared to animals that
were not given bromhexine therapy. This proved that bromhexine
effectively enhanced one of the changes in vitro diabetic
nephropathy. [43] On the other hand, in a study performed by
Marshall et al. in 1991, the activity of 72 mg of bromhexine daily
was observed in nine insulin dependent diabetes melitus patients
with normal albumin excretion in a randomised cross over double
blind clinical trial. There was no change in the albumin excretion
after bromhexine treatment in all the three groups tested with no
change in blood pressure, blood glucose levels or creatinine
clearance. Thus, they concluded that bromhexine had no effect in
insulin dependent diabetes mellitus patients. [44]
Twenty five patients suffering from xerostomia after head and
neck radiotherapy were given a treatment of pilocarpine and
bromhexine in a randomized crossover single blind clinical trial.
Initially, they were given pilocarpine for a period of 2 weeks
followed by a wash out period of one week. Then, they were given
bromhexine for the subsequent 2 weeks. In the second part of the
clinical trial, patients were first asked to consume bromhexine
and then pilocarpine for a period of 2 weeks each along with a gap
of one week wash out period in between. The results were
analyzed based on the saliva secretion rates of patients.
Pilocarpine proved more effective in treating xerostomia as
correlated with bromhexine. However, bromhexine also showed
effective results alone but was more productive in reducing
radiotherapy associated problems when used in combination
with pilocarpine. [45]
On the basis of the above mentioned descriptive studies
highlighting the role of bromhexine in various clinical conditions,
it can be stated that bromhexine has been effective in most of the
cases when administered to people. It has been proven to be a
suitable molecule that alters the mucus properties and has been
helpful in easing many clinical conditions like asthma, bronchitis,
nephropathy and xerostomia. The trend of research on this
observed in these patients. [34] As put forward by Lal and Bhalla,
forty one patients with chronic bronchitis were given 16 mg
bromhexine or placebo thrice daily for 3 weeks along with 500 mg
oxytetracycline twice daily. These patients also had symptoms of
irreversible airways obstruction. Thirty six patients showed
reduction in stickiness of phlegm whereas five patients had
developed influenza. There was no significant change in other
respiratory illnesses such as cough, sputum volume and ease of
breathing. [35]
As reported by Aylward, bromhexine was compared with S-
carboxymethylcysteine in a clinical study in patients having
mucoid sputum for 10 days. Both the drugs were given orally as
syr up fo rm ulat io ns t hr ice d aily a s 7 50 mg f or S-
carboxymethylcysteine and 16 mg for bromhexine. There was a
prominent change in cough severity, consistency of sputum and
expectoration ease. However, bromhexine didn't show any overall
benefits in the respiratory states and thus was not prefered by
clinicians. One person had also shown side effects of severe
nausea after receiving bromhexine. [36] Armstrong posited that
there were beneficial results after consuming bromhexine
(Bisolvon) which was used for the treatment of chronic
bronchitis. There were prominent amendments in the sputum
volume, consistency, peak expiratory flow rate and ascultatory
findings. This proved that bromhexine was effective for most
people with thick sputum. [37] In a double cross blind clinical
trial, thirty patients were randomized for 36 mg of bromhexine
and 45 mg of ambroxol (metabolite VIII of bromhexine). Several
parameters of mean bronchial flow resistance, arterial blood
gases, forced expiratory volume, static lung volumes and
laboratory results were analyzed. However, bromhexine didn't
cause a change in any of the lung parameters. [38]
In Greek medicine several early remedies such as cinnamon,
garlic, pepper, turpentine etc. have been replaced with the
modern mucokine tic re medies o f ephedr ine, a tropine ,
theophylline and bromhexine. [39] The efficacy of bromhexine
therapy was observed in the treatment of eighty eight patients
who were diagnosed with bronchiectasis, by administering them
with 30 mg capsules of bromhexine or placebo thrice daily in
conjunction with ceftazine for one week. Bromhexine produced
effective results and improved the respiratory conditions of
patients. [19] In a one-week, multicentric and randomised
double-blind clinical study, four hundred twenty six patients with
progressive coughing were tested for the efficacy and tolerability
of three expectorant formulations for three times per day for 7
days. Group A were given a fixed dose concentration of 2 mg
salbutamol, 100 mg guaiphenesin and 8 mg of bromhexine HCl.
There was a significant improvement in the reduction of cough
frequency and several sputum characteristics. Group B were
administered with a combination of 100 mg guaiphenesin and 2
mg salbutamol. Group C were given a combined dosage of 8 mg
bromhexine HCl and 2 mg salbutamol. Both groups B and C didn't
produce effective results as compared to group A. [40] This
further affirmed that the combination of salbutamol, bromhexine
and guaiphenesin over bromhexine or guaiphenesin given alone,
could be used effectively as a cough expectorant for alienating the
cough produced.
4.2.1 Nil effects of bromhexine for chronic bronchitis studies
Langlands in 1970 reported that 8 mg Bromhexine or identical
placebo tablets were administered in patients with chronic
Ayushi Bhagat & Rachana/Int J Biol Med Res.9(3):6455-6459
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5. Molina L. Use of Na-274 in bronchopneumonia in infants. Med Klin. 1970;
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effect of bromhexine on phospholipid concentration in bronchial and
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7. Matts SGF, Zorbala-Mallios H, Southgate J. Sputum fibre systems in
exacerbations of longstanding pulmonary disease. A comparison of
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molecule has slowed down these days and it is important to
analyze this molecule further by focusing on the optimization of
its drug regime with dose, time intervals, frequencies and
combinations with other drug to enhance its efficacy in the above
stated clinical conditions along with several unexplored diseased
Ayushi Bhagat & Rachana/Int J Biol Med Res.9(3):6455-6459
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The effect of bromhexine on experimentally induced diabetic nephropathy.
Br J Exp Pathol. 1983; 64(4):462-465.
All rights reserved.
Copyright 2010 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685.
44. Marshall SM, Shearing PA, Shelley JH, Alberti KG. The effect of bromhexine on
albumin excretion in insulin dependent diabetes. Diabete Metab. 1991;
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Improving Radiotherapy-induced Xerostomia. J Dent Res Dent Clin Dent
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Ayushi Bhagat & Rachana/Int J Biol Med Res.9(3):6455-6459
... Ambroxol, bromhexine and acetylcysteine from mucolytic drugs were tested. They are one of the most commonly used mucolytic drugs in upper respiratory tract infection with thick secretions [9][10][11][12][13]. The general mechanism of action of the studied drugs is to dilute secretions in the bronchial tree by stimulating the secretion of surfactant in the lungs, breaking down mucus glycoproteins into smaller particles and stimulating ciliary movement in the bronchi [9][10][11][12][13]. ...
... They are one of the most commonly used mucolytic drugs in upper respiratory tract infection with thick secretions [9][10][11][12][13]. The general mechanism of action of the studied drugs is to dilute secretions in the bronchial tree by stimulating the secretion of surfactant in the lungs, breaking down mucus glycoproteins into smaller particles and stimulating ciliary movement in the bronchi [9][10][11][12][13]. In addition, acetylcysteine has antioxidant activity, thanks to which it neutralizes free radicals formed in respiratory cells during the inflammatory process [14]. ...
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The drugs except active pharmaceutical ingredient (API) contain excipients in formulations. In drugs formulations, it is important that API and excipient are compatible. As a quick and cheap method of testing the compatibility of API with an excipient, thermal methods can be used, including thermogravimetry analysis. In this study, the assessed compatibility of selected mucolytic drugs (ambroxol, bromhexine, acetylcysteine) with excipients (magnesium stearate, lactose monohydrate, starch) is used in solid dosage form. TG and DTG analysis were done for pure API, excipients, and binary mixture API/excipient with different ratio. The study has shown that the tested mucolytic drugs are compatible with magnesium stearate, but are incompatible with lactose monohydrate. The Maillard reaction is responsible for this incompatibility, which was additionally confirmed by a colorimetric method. The starch and acetylcysteine are compatible, but starch and ambroxol are incompatible. The measurements for compatibility bromhexine witch starch are ambiguous. The obtained results proved the usefulness of TG and DTG measurements for initial examination of compatibility API/excipient in preformulation studies.
... It is a mucolytic drug used in curing respiratory disorders combined with excessive or viscid mucus secretion and cough. Its secretolytic expectorant action appeared by acting on the mucus at its formative stages inside the mucus-secreting cells present in glands, enhancing the production of thinner and less viscous mucus in the respiratory tract, which is easily cleared and expectorated by the cilia out of the lungs (2). Impurity B (IMB) is chemically identified as 2-amino-3,5dibromobenzaldehyde (1) (Supplementary Figure S1b). ...
Two simple, sensitive and validated chromatographic methods were developed for quantitative determination of bromhexine hydrochloride (BHX) in presence of its major impurities, impurity B (IMB) and impurity C (IMC), as specified by British Pharmacopoeia. First method (I) was high-performance thin layer chromatography-densitometry at which the chromatographic separation was performed using silica gel plates and developing system consisted of hexane:acetone:ammonia solution (9:0.5:0.08, by volume) with ultraviolet scanning at 240 nm and linearity was achieved in the ranges of 0.40–10.00, 0.20–2.00 and 0.20–2.00 μg/band of BHX, IMB and IMC, respectively. Also, second chromatographic method (II) was high-performance liquid chromatography (HPLC) where the separation was carried out on C18 column at isocratic mode at flow rate 1.5 mL/min. The mobile phase consisted of methanol:water (90:10, v/v) adjusted to pH 2.5 with O-phosphoric acid and temperature was adjusted to 40°C. The scanning wavelength was 240 nm. The chromatographic run time was 6 min. Linearity of this method was achieved in the ranges of 4.00–40.00, 0.20–10.00 and 0.50–10.00 μg/mL for BHX, IMB and IMC, respectively. The validation of these chromatographic methods was made according to International Conference on Harmonization guidelines. These methods were successfully applied for determination of BHX in its pharmaceutical formulation. Also, statistical comparison was attained between the developed methods and the reported HPLC method using Student’s t-test and F-test, and the obtained results showed that there was not any significant difference between them concerning with accuracy and precision.
... The mechanism of action is based on the breakdown of phlegm, improves the production of serous mucus in the respiratory tract, and makes the phlegm less viscous. This contributes to a secretomotor effect by helping the cilia to expel phlegm out of the lungs (Bhagat and Rachana 2018). This activity was demonstrated when there was an increase in the concentration of phenol red in the tracheobronchial secretions of the experimental animals, which is reflected by the different absorbances. ...
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Sarmiento-Tomalá GM, Miranda-Martínez M, Chóez-Guaranda IA, Gutiérrez-Gaitén YI, Delgado-Hernández R, Carrillo-Lavid G. 2020. Pharmacognostic, chemical and mucolytic activity study of Malva pseudolavatera Webb & Berthel. and Malva sylvestris L. (Malvaceae) leaf extracts, grown in Ecuador. Biodiversitas 21: 4755-4763. Among the cultivated and/or native plant species of Ecuador, are those belonging to Malvaceae. Of these, the most traditionally used are Malva pseudolavatera Webb & Berthel. and Malva sylvestris L., which are grown and sold in indigenous markets. Various articles have been published for M. sylvestris about its chemical composition and pharmacological properties; however, M. pseudolavatera lacks references and is the most commercialized in Ecuador. Therefore, this work sets the following objective: To carry out a comparative study of the pharmacognostic, chemical and mucolytic activity of the species M. pseudolavatera and M. sylvestris. The species studied were collected in the province of Chimborazo. Extracts were obtained with different solvents: water, hexane and 80% ethanol. The aqueous extract was used to determine the mucolytic activity; the hexane and alcoholic extracts were analyzed by the coupled gas chromatography-mass spectrometry system. It was found that M. pseudolavatera has a very similar chemical composition to M. sylvestris; The presence of fatty acids, di and triterpenoids, phytosterols and abundant amino acids was detected. Both species showed an important mucolytic effect, the activity of M. pseudolavatera being higher than the highest doses tested. These studies provide scientific data that allow demonstrating the high potentiality of extracts from the leaves of two Malva species as sources of plant material for possible research and development of phytotherapeutic products with mucolytic and gastroprotective activity in correspondence with their uses in traditional Ecuadorian herbal medicine.
... It was developed in the research laboratory of Boehringer Ingelheim in the late 1950s as an active ingredient for pharmaceutical use. It was then introduced in 1963 under the trademark of Bisolvon® [10]. BHH is chemically known as N-(2-Amino-3,5-dibromobenzyl)-Nmethylcyclohexanamine hydrochloride, and it is a white or almost white crystalline powder [11]. ...
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A simple, fast, and sensitive spectrophotometric method was suggested for the determination of Bromhexine Hydrochloride (BHH) in its pharmaceutical formulations. The method depends on the diazotization of BHH by sodium nitrite in acidic medium to produce the corresponding diazonium salt. The latter is coupled with phloroglucinol reagent in alkali medium to form a yellow water soluble azo-dye which has a maximum absorption at 405 nm with a molar absorptivity of 2.7×104 and Sandellʼs sensitivity of 0.01517 µ Beerʼs low is obeyed within a concentration range of 0.25-15 µg.mL-1 of BHH. The LOD and LOQ values of the proposed method were 0.087 µg.mL-1 and 0.293 µ, respectively. The proposed method was validated with standard methods and successfully applied to the determination of Bromhexine in its pharmaceutical formulations as tablets, syrup, and injections.
... Meanwhile only few adverse effects of bromhexine are reported such as nausea, vomiting, diarrhea and fever. For these reasons, bromhexine is a safe drug (15). Similarly, the study by Habtemariam et al approved the efficacy of bromhexine as a prophylactic drug against COVID-19 (16). ...
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Bromhexine as a fluidifying agent can be investigated in clinical trials to discover its therapeutic effect on respiratory involvement following COVID-19.
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Pneumonia merupakan salah satu penyebab kematian utama pada anak balita di dunia, selaras dengan pernyataan badan kesehatan dunia (2013) yang menyatakan bahwa kejadian kematian akibat pneumonia pada anak masih menjadi salah satu masalah utama, khususnya di negara berkembang dan dijuluki ”the forgotten killer of children”. Terapi pneumonia memerlukan biaya yang cukup besar. Tingginya biaya pengobatan membuat pemerintah melahirkan solusi dengan menerapkan sistem Jaminan Kesehatan Nasional (JKN) untuk meringankan beban ekonomi masyarakat. Penelitian ini bertujuan untuk melakukan komparasi tarif klaim INA-CBGs dengan tarif riil yang dikeluarkan oleh rumah sakit. Metode penelitian menggunakan deskriptif analitik dengan pendekatan cross sectional. Populasi dalam penelitian ini ialah data rekam medis dan data administrasi kuangan pasien pneumonia anak di Sakit X Kota Madiun dari 2019-2021. Sampel yang digunakan ialah berkas rekam medis pasien yang memenuhi kriteria inklusi. Pengambilan sampel menggunakan metode purposive sampling. Ditemukan perbedaan yang signifikan antar rata-rata total biaya medis langsung pasien pneumonia anak rawat inap kategori ringan (J-4-16-I) pada kelas perawatan III dengan tarif INA-CBG’s di Rumah Sakit X Kota Madiun (p<0,05). Besar selisih yang diperoleh pada perbandingan tarif INA-CBG’s pada rata-rata total biaya riil pasien pneumonia anak kategori ringan pada kelas perawatan III sebesar Rp. -1.293.583.
Bromhexine is a synthetic molecule derived from the natural product vasicinone isolated from Adhatoda vasica, an important ayurvedic medicinal plant. Bromhexine was validated as an active ingredient for pharmaceutical use at Boehringer Ingelheim and was introduced in 1963. Bromhexine is widely prescribed as OTC mucoactive drug to treat a broad range of respiratory diseases. The mechanism of action of bromhexine is primarily associated with its secretomotoric effect through expectorating the mucus out of the lungs with the modification in the physiochemical features of mucus. Bromhexine has been recently in the spotlight for its possible application as a repurposing drug candidate for the management of COVID-19 patients. In this chapter, we have provided a perspective for the application of bromhexine in COVID-19 patients based on the safety assessment, mechanistic findings, and reports from many clinical trials around the world. The chapter also tried to shed light on the therapeutic aspects of bromhexine in different disease conditions.
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Background and aims. Xerostomia is one of the most common complications of head and neck radiotherapy. The aim of this study was to evaluate and compare the efficacy of pilocarpine and bromhexine in improving radiotherapy-induced xerostomia and its associated symptoms. Materials and methods. In this single-blind, randomized crossover study, pilocarpine and bromhexine tablets were used by twenty-five patients suffered from xerostomia, with a medical history of head and neck radiotherapy. At step A, the patients were treated with pilocarpine for 2 weeks. In addition, they were asked to take bromhexine for 2 weeks with a one-week washout period. At step B, the inverse process was conducted (first bromhexine, then pilocarpine). Whole resting saliva was collected from patients before and after receiving each medication by precise measurements. Then, efficacy of the two drugs in the treatment of xerostomia and its related oral complications was evaluated using questionnaires by Dichotomous format. The results were statistically analyzed using t-student and Fisher’s exact and chi-squared tests. Statistical significance was set at P<0.05. Results. The difference between saliva secretion rates before and after medications was not significant for bromhexine users at two steps of the study (P=0.35); however, it was significant for pilocarpine users (P=0.0001). Users of both drugs showed significant differences in improvement of xerostomia, chewing, swallowing, tasting and mouth burning. Conclusion. Pilocarpine is probably more effective in improving xerostomia and its associated problems compared with bromhexine, although the use of the latter was also shown to ease some of the consequences of radiotherapy in the head and neck region.
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Patients with acute bronchitis, acute exacerbations of chronic bronchitis and asthmatic bronchitis suffer from cough with tenacious bronchial secretions requiring expectorants in addition to bronchodilating therapy. The present one-week, multicentric, prospective, randomised, double-blind study compared the efficacy and tolerability of three expectorant formulations in 426 patients with productive cough associated with varied aetiology after approval by the institutional review boards. Selected patients received 7 days' treatment with either fixed dose combination (FDC) of salbutamol 2 mg + bromhexine HCI 8 mg + guaiphenesin 100 mg (group A) or salbutamol 2 mg+ guaiphenesin 100 mg expectorant (group B) or salbutamol 2 mg + bromhexine 8 mg (group C) thrice daily after obtaining their informed consent. In group A, there was improvement of symptoms in a larger number of patients and earlier onset of action in reducing cough frequency and severity and improving sputum characteristics as compared to the other two groups. More patients in group A reported excellent efficacy (44.4%) as compared to only 14.6% in Group B and 13% in Group C. Cough expectorant containing salbutamol + bromhexine +guaiphenesin could be the expectorant of choice in alleviating productive cough since it scored in terms of efficacy as well as tolerability over salbutamol with either bromhexine or guaiphenesin alone.
The sputum fibre systems of 53 patients were studied during exacerbations of their existing pulmonary disease. Serial specimens of sputa were examined and demonstration of the mucopolysaccharides (MPS) and desoxyribonucleic acid (DNA) fibre systems were made and changes in them closely observed. Results showed that the quantity and the viscosity of the sputum were greatly influenced by fibre systems and that there was a difference between the two fibre systems. When patients responded to antibiotics the DNA fibres disappeared within a week. Patients whose bacteria were insensitive to antibiotics revealed failure of the DNA fibres to disappear, and prediction of bacterial insensitivity could be made from this. Patients treated with bromhexine (Bisolvon) showed a significant reduction in MPS fibres with the fibres disappearing altogether usually within 7 to 12 days of starting treatment. Patients treated by antibiotics alone were sometimes not improved and the volume and viscosity of sputum were unaffected. This was shown to be due to persistance of the MPS fibres. Results indicate that some of the flare-ups of chronic chest disease are not related to infection but are brought on by increase in the viscosity of sputum due mainly to the presence of MPS fibres. The viscosity of the sputum and the volume of it can be reduced by bromhexine treatment. The rôle of infection and other factors in flare-ups of chronic respiratory disease is discussed and the importance of the techniques on the study of fibre systems considered.
One hundred patients ranging in age from 2 to 13 years and suffering from acute or recurrent respiratory tract infections were treated with cephalexin and bromhexine administered simultaneously three times daily for periods varying from 5 to 12 days. The clinical and bacteriological results were excellent. The treatment induced positive changes in both clinical and haematological parameters: 93 patients were cured or showed clinical improvement. No side-effects were observed except in three patients with slight gastric intolerance.
237 out-patients suffering from chronic obstructive lung disease (COLD) were selected from 7 Italian clinical centers. They were randomly allocated to either placebo or bromhexine 30 mg b.i.d. p.o., in a double-blind fashion. Sputum volume and quality, facility of expectoration, cough, dyspnea, auscultatory thoracic symptoms, forced expiratory volume, peak expiratory now rate and residual volume were evaluated. Bromhexine showed a statistically significant therapeutic activity in comparison to placebo. This action was rapid, marked and effective in determining a modulation of bronchial secretions.
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