The future cough remedy

 Acebrophylline is an airway muco-

regulator and anti-inflammatory agent.
 The molecule contains Ambroxol,
which facilitates various steps in
the biosynthesis of pulmonary
surfactant, theophylline-7 acetic
acid whose carrier function raises
blood levels of Ambroxol, thus
rapidly and intensely stimulating
surfactant production.
Acebrophylline: Mechanism of action
Solid-state chemistry of Ambroxol theophylline-7-acetate

Anastasia Foppoli 1 , Lucia Zema 1 , et.all

Abstract:
Ambroxol theophylline-7-acetate (ACE) is the salt obtained by reaction of equimolar
amounts of ambroxol (AMB), a drug showing mucolytic and expectorant properties, and
theophylline-7-acetic acid (TAA), a xanthine derivative with specific bronchodilator activity.
ACE is used for the treatment of bronchial and pulmonary diseases (bronchitis, asthma,
emphysema, chronic obstructive disease). Recrystallization experiments of ACE resulted in
the isolation of two polymorphs (monotropically related) and four solvated forms. X-ray
diffractometry, DSC, TGA, and HSM techniques were used to investigate the forms that are
obtained by thermal desolvation of the solvates. The phase diagram of the TAA-AMB binary
system was constructed by performing thermal analyses on mixtures of TAA-AMB and of
each component plus the interaction compound (TAA-ACE and ACE-AMB). The Schroeder-
Van Laar equation proved to be a very useful tool for checking the consistency between the
experimental data and the theoretical model related to the general system, showing
complete miscibility in the liquid phase and complete immiscibility in the solid phase.

© 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1139-1146, 2007
AUC… 792 ng/ml
Cmax of 125ng/ml
Tmax was - 4.0 (- 22.9 ~ 14.9).

This satisfies the bioequivalence criteria of the

European Committee for Proprietary Medicinal
Products and the US Food and Drug Administration
Guidelines.
Clinical Trials on Acebrophylline
J Int Med Res. 1996 May-Jun;24(3):302-10.

Effects of a short course of treatment with Acebrophylline on the

mucus rheological characteristics and respiratory function
parameters in patients suffering from chronic obstructive pulmonary
disease.
Agliati G. Vaprio d'Adda Hospital, Medical Department, Milan, Italy.

Method:
A total of 30 patients (27 males and 3 females) with a mean age of 62.6 +/- 3.9
years, suffering from chronic obstructive pulmonary disease were recruited into this
open study to evaluate the clinical efficacy and the safety of a short course of
treatment with 100 mg Acebrophylline, twice daily for 14 days. To assess the
effectiveness of the drug, symptoms and signs, such as cough intensity and
frequency, auscultatory pattern, dyspnoea, cyanosis, difficulty of expectoration,
sputum quantity, appearance and density, were evaluated at baseline and after 1,
3, 5, 7, 10 and 14 days of therapy. In addition the rheological properties of the
bronchial mucus (viscosity and spinnability) were measured and respiratory
function tests were performed before and after treatment.
Result:
There was a progressive improvement of all evaluated symptoms and
signs, resulting in improvement of the auscultatory pattern, as well as
dyspnoea. This was accompanied by improvement or normalization of the
respiratory function indices, which showed statistically significant
differences (P < 0.01) between the baseline and the endpoint values, apart
from total lung capacity. Blood-gas analysis demonstrated a significant
increase of PaO2 and a significant decrease of PaCO2 values at the end of
the treatment period (both P < 0.01).
Conclusion:
In general, acebrophylline was well tolerated. No clinically relevant or
significant changes in any of the routine laboratory parameters were found
on comparing the values obtained before and after treatment. Only three
patients complained of epigastric pain, but this was not so severe or long-
lasting as to require the discontinuation of the treatment.
Clin Ther. 1985;7(6):733-6.

Therapeutic activity of ambroxol theophyllinacetate in

chronic obstructive pulmonary diseases.
Primbs K.

Method:
In an open study, 50 patients suffering from chronic obstructive pulmonary
disease in an acute infectious phase were treated with ambroxol
theophyllinacetate. The drug was given orally in a dosage of 100 mg BID for
ten days.
Result:
Viscosimetric data showed a significant decrease of viscosity of the mucus,
leading to easier expectoration and reduction in the severity and frequency of
cough.
Conclusion:
These improvements had positive effects on respiratory function and on the
condition of the patients.
Arzneimittelforschung. 1988 Jun;38(6):828-30.

Modification of mucociliary clearance by a combination of theophylline

with ambroxol and of ambroxol in monotherapy

Dorow P, Weiss T. Abteilung für Kardiologie und Pneumologie, Freien Universität Berlin.

Influence on Mucociliary Clearance by a Theophylline-

Ambroxol Combination and by Ambroxol in Monotherapy.

Method:
In a controlled randomised double-blind study the influence of theophylline + ambroxol
(TA) and ambroxol (A) on lung function and mucociliary clearance was investigated. 19
patients with chronic obstructive lung disease were treated after a 5-day wash-out
period for 5 days with TA (700 mg theophylline, 60 mg ambroxol/d) or A (60 mg
ambroxol/d), respectively. Measurements were done on the 5th and 10th day.
Result
Under the treatment with TA a marked improvement of lung function was observed.
Conclusion:
The mucociliary clearance improved under treatment with TA and A, with TA being
significantly better compared with treatment group A.
A Review of Acebrophylline …an airway mucoregulator and
anti-inflammatory agent.
Monaldi archives for chest disease 2007, vol. 67, no2, pp. 106-115 [10 page(s) (article)]

Pozzi E.

Acebrophylline is an airway mucus regulator with anti-inflammatory action. The

drug's approach involves several points of attack in obstructive airway disease. The
molecule contains Ambroxol, which facilitates various steps in the biosynthesis of
pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood
levels of Ambroxol, thus rapidly and intensely stimulating surfactant production.
The resulting reduction in the viscosity and adhesivity of the mucus greatly
improves ciliary clearance. By deviating phosphatidylcholine towards surfactant
synthesis, making it no longer available for the synthesis of inflammatory mediators
such as the leukotrienes, Acebrophylline also exerts an inflammatory effect. This is
confirmed in vivo by the reduction in a specific bronchial hyper-responsiveness in
patients with stable bronchial asthma. On a clinical level, Acebrophylline is
therapeutically effective in patients with acute or chronic bronchitis, chronic
obstructive or asthma-like bronchitis and recurrence of chronic bronchitis; it
reduces the frequency of episodes of bronchial obstruction and reduces the need
for beta2-agonists, and improves indexes of ventilatory function.
It is estimated that the Asthma and
COPD market in INDIA is around
370-380 Crs growing at around 5-
10%.
In this market the share of Ambroxol
is around 8-10%.
This becomes a lucrative market to
launch Acebrophylline.
Brand: SURFOLASE Company
Switzerland.

Indication: Expectorant. Bronchodilatator and mucolytic agent.

Presentation: 50 - 100 mg capsules, 25 - 100 mg sachets, 120 -
200 ml syrup
Brand: BUROPHIL Country Korea

Indication: Expectorant. Bronchodilatator and mucolytic agent.

Presentation: 50 - 100 mg capsules, 25 - 100 mg sachets, 120 -
200 ml syrup

In India approved by DCGI

Product : Acebrophylline capsules 100mg
Indication: For the treatment of adult patients with chronic
obstructive pulmonary disease and bronchial asthma
Approved on 29.05.08
Proposed Formulation in Syrup Form:

Syrup
Each 5ml of syrup would contain
Acebrophylline 50mg.
Guaiphenesin 250mg.
Menthol 0.5mg
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Marketing off:
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