MXPA05007024A - Solid, semisolid pharmaceutical composition in suspension, emulsion and aqueous solution or syrup, containing ambroxol hydrochloride, loratadine and salbutamol sulfate. - Google Patents

Abstract

The present invention refers to formulations in different pharmaceutical forms comprising (a) Ambroxol Hydrochloride, (b) Loratadine, (c) Salbutamol Sulfate, (d) one or more anti-adhesive agents, (e) one or more disintegrating agents, (f) one or more binding agents, (g) one or more lubricating agents, (h) one or more diluting agents, (i) one or more flavouring and/or essence agents, (j) one or more surfactant agents, (k) one or more moisturizing agents, (l) one or more suspending agents, (m) one or more sweetening agents, (n) one or more flocculating agents, (o) one or more preservative agents, (p) one or more antimicrobial agents, (q) one or more pH buffer systems, (r) one or more solvents and/or vehicles, (s) one or more tonic agents, (t) one or more antioxidant agents, (u) one or more chelating and/or complexing agents, (v) and any additive useful for the formulation. The present invention further provides a method for the treatment of bronchospasms in patients suffering from airwa y reversible obstructing diseases, as well as an expectorant, surfactant, mucolytic and antihistaminic action.

Description

SOLID PHARMACEUTICAL FORM, SEMISOLIDE, IN SUSPENSION, EMULSION, SYRUP OR SOLUTION CONTAINING AMBROXOL CHLORHYDRATE, 10RATADINE AND SALBUTAMOL SULFATE " FIELD OF THE INVENTION The rise of asthma in the world, particularly with symptoms in the pediatric age, stimulates the study of associations of drugs that may be complementary given the pathophysiology of the disease. Therefore, the present invention relates to new pharmaceutical formulations containing as active ingredients Ambroxol Hydrochloride, Loratadine and Salbutamol Sulfate, as well as one or more anti-adherent agents, one or more disintegrating agents, one or more binding agents, one or more agents lubricants, one or more diluting agents, one or more flavoring agents and / or essences, one or more surfactants, one or more wetting agents, one or more suspending agents, one or more sweetening agents, one or more flocculating agents, one or more more preservatives, one or more antimicrobial agents, one or more buffer systems, one or more solvents and / or vehicles, one or more toning agents, (s) one or more antioxidant agents, one or more chelants and / or complexing agents , and any other additive necessary for the formulation.

BACKGROUND OF THE INVENTION In asthma, the limitation to airflow is due to several causes, among which are: inflammation, edema and remodeling of the bronchial mucosa, increase in the production of bronchial secretions with the formation of mucus plugs, as well as Hyperreactivity of smooth bronchial musculature, which results in acute bronconstriction, all these events in a significant number of cases are triggered by an allergic component. Allergic rhinitis is a risk factor for the development of asthma, and conversely, asthma is frequently found in patients with rhinitis (17-25% in children and 20-50% in adults). More than 80% of patients with asthma have allergic, non-allergic rhinitis or both. Antihistamines competitively inhibit most of the pharmacological actions of histamine.

According to historical recognition, the term antihistamine is used to describe drugs that act as receptor antagonists. There is currently considerable evidence implicating histamine in the pathogenesis of asthma. (There are enough studies that demonstrate the efficacy of antihistamines in the regulation of several physiopathogenic factors involved in asthma: inhibition of activated eosinophils and T cell recruitment, membrane stabilization, decrease of inflammatory mediators, decrease in bronchial reactivity, inhibition of intracellular phosphodiesterase, decreased airway resistance, antihistamines have been used in the management of bronchial asthma (Antihistamines in childhood asthma, Dr. José Miguel Escamilla, Pediatrician, Pulmonologist, University of Cartagena).

The use of loratadine reduces nasal symptoms, all these causes are related to the inflammatory response of the airway.

This hypersecretion in subjects with asthma, and especially during exacerbations, allows us to theorize that a drug with effect on these secretions could be useful adding to the anti-inflammatory and antihistamine bronchodilator therapy that these patients require.

The secretions of the airways in subjects with asthma are not only increased in volume when compared with normal subjects; the secretions also differ in the viscoelastic and rheological properties. These qualitative and quantitative differences are thought to stem both from the infiltration of the airway wall by inflammatory cells and from the pathological changes of the secretory cells and blood vessels in the submucosa and the airway epithelium. The abnormal hardness and adherence of these secretions are not due solely to an excess of mucin production, but also to the desquamation of epithelial cells, to the flight of albumin from the bronchial microvasculature, to the basic protein derived from eosinophils, and to the DNA released from inflammatory cells by lysis. These changes influence the occasional finding of bronchial molds of thick mucus in the sputum of patients with asthma, as well as the finding of Charcot-Leyden crystals, resulting from the degeneration of eosinophils, or from the bodies of Cróela due to the grouping of desquamated epithelial cells. The obstructive component that occurs at the expense of mucus hypersecretion can reduce the efficacy of inhaled therapies, both anti-inflammatory and bronchodilator and antihistamine. Due to this hypersecretion, it is common to observe the formation of segmental and subsegmental atelectasis in the courses of severe asthmatic crises.

Ambroxol is a synthetic drug used for two decades as an expectorant and stimulant of the production of pulmonary surfactant. The expectorant effect of Ambroxol is due to an increase in the secretion of water by the bronchial epithelium, secondary to the inhibition in the absorption of sodium, which results in an increase in the volume of the mucus with a concomitant reduction in viscosity, which significantly improves mucociliary function2.

SUMMARY OF THE INVENTION According to the above, for the applicant there is an interest in the development of new formulations in different pharmaceutical forms containing Ambroxol Hydrochloride, Loratadine and Salbutamol Sulfate.

Thus in a first aspect, the present invention provides new pharmaceutical formulations comprising: (a) Ambroxol Hydrochloride, (b) Loratadine, (c) Salbutamol sulfate, (d) one or more anti-adherent agents, (e) one or more disintegrating agents, (f) one or more binding agents, (g) one or more lubricating agents, (h) one or more diluting agents, (i) one or more flavoring agents and / or essences, (j) one or more agents surfactants, (k) one or more wetting agents, (1) one or more suspending agents, (m) one or more sweetening agents, (n) one or more flocculating agents, (ñ) one or more preservatives (or) one or more antimicrobial agents, (p) one or more buffer systems, (q) one or more solvents and / or vehicles, (r) one or more toning agents, (s) one or more antioxidant agents, (t) one or more chelants and / or complexing agents, (u) and any other additive necessary for the formulation.

In a second aspect, the present invention provides a method for the treatment of bronchospasm in patients with reversible obstructive airways disease, as well as an expectorant, surfactant, mucolytic and antihistaminic action.

DETAILED DESCRIPTION OF THE INVENTION Definitions: The solid dosage forms are preparations containing the active ingredient (s) and additives generally in discoid form, grooved or non-grooved and of varying size obtained by compression of powders or granules, in capsules, patches, ovules, pearls, suppositories, troches or pills.

A suspension is a two-phase system consisting of a finely divided solid dispersed in a solid, a liquid or a gas. An emulsion is a heterogeneous system consisting of two immiscible liquids, in which the dispersed phase is composed of small globules distributed in the vehicle in which they are immiscible. The active ingredient (s) can be in the external or internal phase. A solution is a liquid, transparent and homogeneous preparation, obtained by dissolving it or the active ingredients and additives in water, and which is used for external or internal use. In the case of injectable, ophthalmic and otic solutions must be sterile solutions. A semi-solid is a preparation that to some extent is a solid; having a stiffness and an intermediate viscosity between a solid and a liquid. A syrup is an aqueous solution with a high concentration of carbohydrates such as sucrose, sorbitol, dextrose, etc. of viscous consistency in which the active ingredient (s) and additives are dissolved.

Salbutamol sulfate is a1 - [[(1,1-Dimethylethyl) -amino] methyl] -4-hydroxy-1,3-benzenedimethanol sulfate and can be represented by the formula (I).

The compound of the formula (I) is known for its pharmacological activity as a bronchodilator which stimulates the adrenergic receptors β2 pulmonary relax the bronchial smooth muscle and decrease the resistance of the respiratory tract.

The Ambroxol Hydrochloride is 4- [[(2-amino-3,5-dibromophenyl) methyl] amino] cyclohexanol hydrochloride and can represent by the formula (II).

The compound of the formula (II) is known for its pharmacological activity as a Mucolytic, expectorant with surfactant action and adjuvant for the relief of broncho-pulmonary processes that occur with increased viscosity and adhesion of the mucus, thanks to its ability to stimulate the secretion and synthesis of surfactant factor, which forms a film throughout the respiratory epithelium, which facilitates the sliding and transport of bronchial secretions to the outside, likewise increases the vibratory power of the ciliary epithelium.

Loratadine is Ethyl 4- (8-Chloro-5,6-dihydro-11H-benzo [5,6] cyclohepta [1,2-J] pyridin-1-ylidene) -1- piperidine-1-carboxylate and can be represented by the formula (III).

The compound of formula (III) is known for its antihistamine activity by providing relief of symptoms associated with allergic rhinitis, such as sneezing, rhinorrhea and pruritus, tearing, as well as relief of the signs and symptoms of chronic urticaria and other allergic dermatological conditions. .

The concentrations of the drugs in the formulation are found in a proportion of 0.001% to 100.0%.

METHOD The applicant below presents a prospective, open study; in which the clinical efficacy of the Salbutamol-Ambroxol-Loratadine combination, which has been administered to treat bronchial asthma in pediatric patients, is described An open, prospective clinical study was carried out. According to preliminary data, a calculation was made of the sample size that determined the requirement of 100 subjects enrolled in this clinical research study, the average age group was 9.12 years, with a range of 6 to 14 years. All of the patients were admitted with an acute exacerbation of bronchial asthma, which was categorized as moderate in 87% of the cases, the other remaining 13% were classified as exacerbation of mild asthma.

All the subjects included in the study were without treatment of bronchodilators, antihistamines or corticosteroids in the six weeks prior to the start of the study.

The criteria used to assess the intensity of the crises were taken from the International Guidelines of the Global Initiative for Asthma (GINA). An initial clinical evaluation was carried out that took into account the following symptoms and signs: Wheezing, productive cough, rhinitis, the characteristics of expectoration. The intensity of each of the symptoms and signs was graded based on an ordinal scale in which the values were: Absent = 0, mild = 1, moderate = 2, severe = 3. The intensity of cough was also assessed in four grades: Absence = 0, low frequency = 1, constant = 2, frequent = 3. Only those that reached a score of 7 or higher were included in the study. Informed consent was requested from the parent or guardian of the minor through an informed consent letter approved by the Local Ethics Committee.

The study was carried out in the outpatient department of the Pediatrics service of the Dr. Ángel Leaño Hospital, during the period from January to March 2004. Laboratory studies were carried out before the start of the therapy and at the end of it ( Complete Hemodynamic Biometrics, Blood Chemistry, General Urine Test, Eosinophils in nasal mucus, chest x-ray and electrocardiogram).

A pulse oximetry was requested in each of the visits, the assigned patients received the combination Salbutamol-Ambroxol-Loratadine in oral solution, administered in bottles of 120 ml at doses calculated per Kg weight per day divided in three doses for 5 days.

Statistic analysis It was performed through two tests: the Chi square test for categorical variables and the Student's T test.

RESULTS We studied 100 patients, the treatment group they received was the Salbutamol-Ambroxol-Loratadine combination. All the patients admitted with a bronchial asthma crisis considered moderate in 77 cases and mild in the remaining 23 cases; all patients presented hyaline rhinorrhoea suggestive of a basic allergic process or with perennial rhinitis data. In the baseline assessment, no significant differences were observed between the groups in terms of intensity of signs and symptoms, with the mean of the score obtained being 9. Similarly, differences between the values obtained in pulse oximetry of 87% were observed. Admission to the project with statistically significant improvement on day 3 and 5 to 92% on average saturation of 02 to ambient air. Regarding the manifestations in the upper respiratory tract, the clinical improvement was evident, establishing itself on the 5th day without rhinorrhea., significantly improving the free passage of air through the upper respiratory tract. The analysis of the clinical data of asthma (dyspnea, wheezing, cough and expectoration), no significant differences were detected, No adverse effects were observed during the study.

DISCUSSION AND CONCLUSIONS The bronchodilator effect of salbutamol has been documented in numerous clinical studies and constitutes one of the expected effects of the treatment. The improvement of wheezing and dyspnea can be explained by the effect of salbutamol on smooth bronchial musculature, which was corroborated through pulse oximetry. It would seem that the additive action of Ambroxol occurs with greater intensity at the level of the small and medium caliber pathways and also seems to be different from the isolated effect of the bronchodilator, this is particularly important in children more than likely in adults, since in those the peripheral areas tend to become more obstructed with an inverse relationship with respect to age. The above marks a difference with the studies carried out in adults that should be highlighted.

This study concludes that the use of the combination improves airflow at the level of the mid-peripheral airways, both by eliminating the obstructive process in the lower airways, and the effect of loratadine in reducing the production of an obstacle in the airways. Upper airways and its bronchodilator effect of salbutamol, it is important to consider it an excellent therapeutic option in children with mild to moderate asthma exacerbations.

The present invention is characterized in that the drugs combined therein can be found as their anhydrous, monohydrated or dihydrated base or as a physiologically acceptable salt.

To give body to the pharmaceutical form can be used a number of ingredients such as: antiadherents, such as: talcum, colloidal silicon dioxide, calcium sulfate, calcium chloride, among others, preferring colloidal silicon dioxide. The release agent must be contained in a proportion ranging from 0.01% to 10.0% with respect to the total weight of the formulation. Disintegrants such as corn starch, modified starches, water soluble cellulose derivatives, croscarmellose sodium, sodium starch glycolate, binders such as gelatin, natural gums, cellulose derivatives, corn starch, rice starch, polyvinylpyrrolidone, povidone, calcium alginate, polientilenglicoles, corn syrup, sucrose, among others, preferring croscarmellose sodium. The disintegrating agent must be contained in a proportion ranging from 0.25% to 20.0% with respect to the total weight of the formulation. Lubricants such as stearic acid, magnesium stearate, talc, among others, with magnesium stearate being preferred. The lubricating agent must be contained in a proportion ranging from 0.01% to 10.0% with respect to the total weight of the formulation.

Diluents such as microcrystalline cellulose, lactose, dextrose, sucrose, fructose, phosphates, among others, with fructose being preferred. The diluent agent must be contained in a proportion ranging from 0.01% to 90.0% with respect to the total weight of the formulation. Surfactants such as poloxamers, sodium lauryl sulfate, docusate sodium, lecithin, polyoxyethylene (20) sorbitan monooleate, among others, the poloxamers being preferred. The surfactant agent must be contained in a proportion ranging from 0.01% to 20.0% with respect to the total weight of the formulation. Humectants can be polar and non-polar, such as ethyl alcohol, water, propylene glycol, polyethylene glycol, glycerol, dimethylacetamide, lecithin, PEG-40 castor oil, butylene glycol, among others, 2-carbon alcohols are preferably used as is alcohol ethyl content in a proportion ranging from 1.0% to 50.0% with respect to the total weight of the formulation excluding it, and polar water is preferred, contained in a proportion ranging from 0.01% to 90.0% with respect to to the total weight of the formulation. Flavors and / or powdered or liquid essences, such as vanilla, cherry, apple, grape, banana, strawberry, mint, pineapple, raspberry, chocolate, coconut, peach, lemon, currant, lime, orange, mandarin, among others, synthetic or of natural origin, cherry and grape flavors being preferred. The flavoring agent (s) must be contained in a proportion of 0.10% to 15% of the total weight of the formulation. Sweetener (s) such as Aspartame, Acesulfame, monosodium glutamate, saccharin, sodium saccharin, among others, with acesulfame and Aspartame being preferred. The sweetening agent must be contained in a proportion ranging from 0.00001% to 5.0% with respect to the total weight of the formulation. Viscosity agents such as guar gum, acacia gum, sodium carboxymethylcellulose, calcium carboxymethylcellulose, bentonite, carbomers, carrageenan, microcrystalline cellulose and sodium carboxymethylcellulose dextrins, hydroxypropylmethylcellulose, hydroxypropyl cellulose, gum tragacanth, xanthan gum, povidone, pectin, methylcellulose, among others , sodium carboxymethylcellulose is preferred. The viscosity agent must be in a proportion ranging from 0.01% to 20.0% with respect to the total weight of the formulation. PH buffer system such as phosphates, citrates, carbonates, bicarbonates, acetates, lactates, among others, with phosphates being preferred. The buffer system must be contained in a proportion ranging from 0.01% to 10% of the total weight of the formulation. Flocculating agent such as sodium chloride, potassium chloride, trisodium citrate, among others, with sodium chloride being preferred. The flocculating agent must be in a proportion of 0.0001% up to 10% of the total weight of the formulation. Antimicrobials such as parabens, thimerosal, sodium benzoate, sorbic acid, potassium sorbate, benzyl alcohol and all the antimicrobials that could be used for these pharmaceutical forms. The antimicrobial should be in a proportion ranging from 0.0001% to 5.0% of the total weight of the formulation. Solvents and / or vehicles such as ethyl alcohol, corn oils, sesame, mineral, cotton, almonds, peanuts and soybeans, glycerin, isopropyl alcohol, polyethylene glycol, propylene glycol, water, sorbitol, ethyl oleate and all solvents and / or vehicles that could be used for these pharmaceutical forms. The solvent and / or vehicle should be in a proportion ranging from 0.001% to 99% of the total weight of the formulation. Toning agents such as dextrose, glycerin, mannitol, sodium chloride and potassium and all the toning agents that could be used for these pharmaceutical forms. The toning agent should be in a proportion of 0.0001% up to 50.0% of the total weight of the formulation. Antioxidant agents such as ascorbic acid, arcorbil palmirate, butyl hydroxytoluene, butyl hydroxyanisole, sodium metabisulphite, tocopherols, sodium thiosulfate and all the antioxidant agents that could be used for these pharmaceutical forms. The antioxidant agent must be in a proportion of 0.001% up to 5.0% of the total weight of the formulation. Chelating and / or complexing agents such as sodium didetate, edetic acid and all the chelating and / or complexing agents that could be used for these pharmaceutical forms. The chelating and / or complexing agent must be in a proportion of 0.001% up to 5.0% of the total weight of the formulation. Sequestering agents such as cyclodextrins and all sequestering agents that could be used for these pharmaceutical forms. The sequestering agent should be in a proportion of 0.001% up to 3.0% of the total weight of the formulation.

The formulation can optionally be coated using methacrylates, cellulose derivatives, combination of polymers and polysaccharides for film coating with aqueous or organic solvents, with dyes, flavors, sugars and any other ingredient that is used for applications of films, coating and dragee, preferring the sufficient quantity until obtaining the desired protection of the pharmaceutical form. The formulation can optionally also be scored or not.

The formulation can optionally be encapsulated in hard gelatine or soft gelatin capsules.

The formulation optionally may further contain other components such as stabilizing agents such as creatinine or dextrin, adsorbents such as bentonite, magnesium carbonate, cellulose powder, dyes and / or pigments such as caramel, ferric oxide, red, yellow, black, mixed they, and all the dyes and / or pigments that could be used for these pharmaceutical forms.

The formulations are contained in containers of adequate capacity which may include a bubble container of P.V.C. (Polyvinyl chloride) from 200 μ to 250 μ that can optionally have a coating of P.V.D.C. (Polivilideno chloride) from 25 g / m2 to 120 g / m2, and adhered with aluminum foil or in celopolymer paper and also in containers of adequate capacity, made of high and / or low density polyethylene, polyethylene terephthalate, polyvinyl chloride , polypropylene, polystyrene, glass type I, II, III and IV, and any other primary packaging, with or without color. The lid can be inviolable, screw cap, cap to cap, child proof, made of high and / or low density polyethylene, polyethylene terephthalate, polyvinyl chloride, polypropylene, polystyrene, with or without color. In addition dosing aids such as dosing spoons, dosing cups, pipettes, syringes, inserts made of materials such as high and / or low density polyethylene, polyethylene terephthalate, polyvinyl chloride, polypropylene, polystyrene, among others, with or without color are included. .

The preparation is carried out by mixing all the components necessary for the formulation.

Examples The following non-limiting examples serve to illustrate the present invention: EXAMPLE 1 1 Ambroxol Hydrochloride 0. 20% w / v 2 Salbutamol Sulfate 0. 05% w / v 3 Loratadine 0. 50% w / v 4 Sucrose 60.00 w / v 5 Polyethylene glycol 2. 00% w / v 6 Polyvidone 4. 00% w / v 7 Citric acid 1. 00 w / v 8 Sodium benzoate 0. 05 w / v 9 Flavor 0. 01% w / v 10 Purified water, cbp 100 .0% w / vo The preparation of the syrup is done as follows: in a proportion of water dissolve the active Ambroxol, Salbutamol and Loratadina. Separately, mix another portion of purified water with Polyethylene glycol, dissolve Sucrose, polyvidone, citric acid, and sodium Benzoate in this mixture. Mix the solution containing the active ingredients and the solution containing Sucrose. Add the flavor and afore the solution to the final volume.

EXAMPLE 2 1 Ambroxol Hydrochloride 0.50% w / w 2 Salbutamol Sulfate 0.20% w / w 3 Loratadine 1.00% w / w 4 Cellulose microcrystalline 25.00% w / w PH 101 5 Croscarmellose sodium 0.10% w / w 6 Magnesium stearate 0.30% w / w The preparation of the capsule is done as follows: Salbutamol, Ambroxol Hydrochloride and Loratadine, PH 101 microcrystalline cellulose and Croscarmellose sodium are mixed. Finally magnesium stearate is added and mixed. The encapsulation is proceeded.

EXAMPLE 3 1 Ambroxol Hydrochloride 0.50% w / v 2 Salbutamol Sulfate 0.20% w / v 3 Loratadine 1.00% w / v 4 Carboxymethylcellulose 10.00% w / v Sodium 5 Silicon dioxide 5.00% w / v Colloidal 6 Poloxamer 188 4.00% w / v 7 Ethyl alcohol 96 ° 2.00% w / v 8 Aspartame 0.01% w / v 9 Acesulfame K 0.01% w / v 10 Flavor 0.50% w / v 11 Sorbic acid 0.01% w / v 12 Sodium chloride 0.50% w / v 13 Water purified, cbp 100.0% w / v 0 The preparation of the suspension is done as follows: in a portion of water dissolve Aspartame, Acesulfame, sorbic acid, Sodium Chloride, Colloidal Silicon Dioxide, Poloxamer 188 and the sodium carboxymethylcellulose. In another portion of water add 96 ° Ethyl Alcohol, Loratadine, Ambroxol Hydrochloride and Salbutamol, shake until complete incorporation. Mix the previous suspension with the solution obtained in the first step and finally add the flavor. Afore.

The Ambroxol Hydrochloride after oral administration, is absorbed quickly and almost completely in the gastrointestinal tract. The bioavailability is 60% since the other 40% of the dose is metabolized in its first step by the liver. It is fixed at 90% to plasma proteins and has a half-life of approximately 9 -10 hours. It is eliminated by the renal route in 85% and 10% is eliminated in an unaltered form.

Loratadine is a powerful long-acting tricyclic antihistamine, which is completely absorbed after oral administration. It has a plasma elimination half-life of 9 hours, but its activity persists for 24 hours. The start of your action is approximately 30 minutes. It is extensively metabolized in the liver and excreted through urine and feces in a maximum period of 10 days. The protein binding is approximately 98%.

Salbutamol Sulfate is a bronchodilator which, after oral administration, is absorbed in the first portion of the duodenum. It is mostly metabolized at the liver level and from there it passes into the bloodstream, reaching the impact cell of the respiratory tree. It is rapidly excreted in the urine (75% of the dose) and in the feces (4%) in a term of 72 hours.

For the treatment of acute and chronic bronchitis, asthma and those processes that occur with retention of secretions and bronchospasm caused by allergic conditions, the use of 120 mg of Salbutamol, 450 mg of Ambroxol and 300 mg of Loratadine daily, divided into 3 is recommended. dose Thus, the present invention provides a pharmaceutical formulation that provides from 3.60 mg to 6.0 mg of Salbutamol, 13.50 mg to 22.50 mg of Ambroxol and 10.80 mg to 18.00 mg of Loratadine per day.

It will be appreciated by those skilled in the art that numerous variations and / or modifications to the invention may be made as shown in specific embodiments without departing from the spirit and scope of the invention as broadly described. Therefore, the present modalities will be considered as illustrative aspects

Claims (8)

NOVELTY OF THE INVENTION Having described the invention as above, property is claimed as contained in the following: CLAIMS

1. A pharmaceutical formulation containing one or more antiadherents which are selected from the group consisting of talc, colloidal silicon dioxide, calcium sulfate, calcium chloride, one or more disintegrants which is selected from the group consisting of corn starch, modified starches , water soluble cellulose derivatives, croscarmellose sodium, sodium starch glycolate, one or more binders selected from the group consisting of gelatin, natural gums, cellulose derivatives, corn starch, rice starch, polyvinylpyridinone, povidone , calcium alginate, polyethylene glycol, corn syrup, sucrose, among others, of one or more lubricants such as stearic acid, magnesium stearate, talc, among others, of a diluent selected from the group consisting of microcrystalline cellulose, lactose , compressible sugar, dexterose, sucrose, fructose, among others. Of surfactants such as poloxamer, sodium lauryl sulfate, docusate sodium, lecithin, among others and humectants that can be polar and non-polar, such as ethyl alcohol, water, propylene glycol, polyethylene glycol, glycerol, dimethylacetamide, lecithin, PEG-40 oil of beaver, butylene glycol, among others, of flavors and / or powdered or liquid essences such as vanilla, cherry, apple, banana, strawberry, mint, pineapple, raspberry, chocolate, coconut, peach, lemon, currant, lime, orange, mandarin, among others, synthetic or of natural origin, in addition to sweetener (s) such as Aspartame, Acesulfame K, monosodium glutamate, saccharin, sodium saccharin, among others, of a viscosity agent such as guar gum, acacia gum, sodium carboxymethylcellulose , calcium carboxymethylcellulose, bentonite, carbomeros, carrageenan, microcrystalline cellulose and sodium carboxymethylcellulose dextrins, hydroxypropylmethylcellulose, hydroxypropyl cellulose, gum tragacanth, gum xantan, p ovidone, pectin, methylcellulose, among others, of a buffer system which is selected from the group consisting of phosphates, citrates, carbonates, bicarbonates, acetates, lactates, among others, of a flocculating agent such as sodium chloride, sodium chloride, potassium, trisodium citrate, among others; of an antioxidant agent selected from the group consisting of ascorbic acid, arcorbil palmirate, butyl hydroxytoluene, butyl hydroxyanisole, sodium metabisulfite, tocopherols, sodium thiosulfate among others; of toning agents such as dextrose, glycerin, mannitol, sodium chloride and potassium, among others, of solvents and / or vehicles such as ethyl alcohol, corn oils, sesame, mineral, cotton, almonds, peanuts and soybeans, glycerin, isopropyl alcohol , polyethylene glycol, propylene glycol, water, sorbitol, ethyl oleate among others, of chelating and / or complexing agents such as disodium edetate (EDTA), ascorbic acid, butylhydroxytoluene (BHT), tocopherols, sodium bisulfite, sodium metabisulfite, among others, antimicrobials such as parabens, thimerosal, sodium benzoate, sorbic acid, potassium sorbate, benzyl alcohol, characterized in that it comprises ambroxol hydrochloride, loratadine and salbutamol sulfate as active ingredients.

2. - A formulation according to claim 1, characterized in that the concentrations of the active ingredients in the formulation are in a proportion of 0.001% to 100.0%.

3. - A liquid pharmaceutical formulation according to claim 1, characterized in that it comprises from 3.60 mg to 6.0 mg of Salbutamol, 13.50 mg to 22.50 mg of Ambroxol and 10.80 mg to 18.00 mg of Loratadine.

4. - A formulation according to claim 1, characterized in that the active ingredients combined therein can be found as their anhydrous, monohydrated or dihydrated base or as a physiologically acceptable salt, with Ambroxol hydrochloride, Salbutamol sulfate and Loratadine base being preferred.

5. - A formulation according to the preceding claims, characterized in that it can be presented in the form of dragee, tablet, coated tablet, a capsule, a suspension, syrup, an emulsion, trocisco or lozenge, solution, preferably being the syrup .

6. - The formulation according to claim 1, wherein the agent for the coating is selected from methacrylates, cellulose derivatives, combination of polymers and polysaccharides for film coating with aqueous or organic solvents, with dyes, flavorings , sugars and any other ingredient that is used for film, coating and dragee applications.

7. - A formulation according to claims 1 to 6, wherein this can be encapsulated in hard or soft gelatin capsules.

8. - Use of the formulation according to claim 1 to 7, for the treatment of acute and chronic bronchitis, asthma and those processes that occur with retention of secretions and bronchospasm caused by allergic conditions.