MXPA04003928A - Albuterol inhalation solution, system, kit and method for relieving symptoms of pediatric asthma. - Google Patents

Abstract

The present invention relates to an albuterol inhalation solution, system, kit and method for relieving bronchospasm in children suffering from asthma. In one alternative embodiment, the solution of the present invention is a sterile, premixed, premeasured single unit dose of albuterol for asthmatic patients 2 to 12 years of age. The present solution may be free of anti-microbial preservatives, such as benzalkonium chloride. In another alternative embodiment, the solution of the present invention comprises about 0.63 mg or about 1.25 mg albuterol.

Description

SOLUTION FOR INHALATION OF ALBUTEROL. SYSTEM. EQUIPMENT AND METHOD FOR RELIEVING SYMPTOMS OF PEDIATRIC ASTHMA CROSS REFERENCE WITH RELATED REQUESTS This application is a continuation in part of the U.S. Patent Application. Serial No. 10 / 034,829, filed on December 27, 2001, which claims priority under the U.S.C. 35 §1 19 (e) of the Patent Application of E.U.A. provisional Serial No. 60 / 348,203 filed on October 26, 2001. The description in all of these prior applications is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION The present invention relates to a solution, system, equipment and method of inhaling albuterol to alleviate the symptoms associated with asthma in children.

BACKGROUND OF THE INVENTION Asthma is a lung disease marked by (1) effort to breathe (2) panting; and (3) cough. Asthma is characterized by: (1) inflammation of the respiratory tract (2) excessive responsiveness of the respiratory tract; and (3) airway obstruction (or reduction of the airways), this is partially or completely reversible, either spontaneously or with treatment. Common symptoms of asthma include panting, shortness of breath, tightness of the chest and a persistent cough. The severity of symptoms varies widely from patient to patient and even from one event (attack) to the other. A key condition of asthma is chronic inflammation of the lining of the lungs. This inflammation is associated with an increase in the sensitivity in the respiratory tract (excessive response capacity) in stimuli such as allergens, irritants, cold air and viruses. When exposed to these actions, the coating suffers an allergic reaction, which causes spasms that constrict the respiratory tract. This bronchoconstriction, in combination with edema and the release of thick secretions, reduces the movement of air through the lungs, resulting in the symptoms commonly associated with asthma. Asthma is the most common chronic lung disease in children. The prevalence of asthma in children has been reported, an increase in the United States of 160%. Hospitalization rates for asthma have risen in young children due, in part, to difficulties in using currently available drug delivery devices and failures to use optimal doses in asthma therapies.

Regardless of the progress in emergency medicine and critique, the pediatric mortality rate of asthma ranges from 0.2 to 0.4 for a population of 100,000, depending on age. Pediatric asthma is ranked as the seventh leading cause of death among children 10 to 14 years of age. Approximately 0.05% of known cases of children with asthma die annually due to this disease. Rapidly activated inhaled beta agonists, such as albuterol, are the first choice of treatment for alleviating the symptoms of acute asthma in children. Albuterol is currently available as an inhalation solution dose unit of 2.5 mg (0.083%) for use in a nebulizer. Although this dose has been approved for use in adults, the FDA has recently extended labeling guidelines to include this amount of albuterol for use in pediatric asthma patients as young as 2 years of age. However, when administered on a regular basis to a child, the 2.5 mg formulation can administer more albuterol than necessary, thereby increasing the risk of adverse effects by the drug. In the recently revised guidelines for the treatment of asthma, the National Institute of Health recommended that pediatric patients use the lowest doses of the beta agonist necessary to control the symptoms. However, the use of lower doses of albuterol in patients under the age of 12 years to reduce the risk of side effects, dilution of currently available medications for asthma is needed. This presents several problems due to parents, caregivers, teachers and others, usually do not have adequate experience to dilute these medications, resulting in inadequate contamination or dosing, among other problems. Also antibacterial preservatives, such as benzalkonium chloride (BAC) are often present in the inhalation solutions used to treat asthma and chronic obstructive pulmonary disease (COPD). The presence of BAC in these solutions generally does not affect the response of the bronchodilator (single dose) in the short term. However, case reports suggest the repeated use of asthma treatments with BAC may result in paradoxical bronchoconstriction. When inhaled by asthmatic individuals, BAC can also produce dose-dependent bronchoconstriction. Regardless of these side effects, many of the commercially available inhaled solutions of albuterol contain BAC. This is, therefore, a need for improved albuterol inhalation solution, system, equipment and method to alleviate the symptoms associated with pediatric asthma.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide an albuterol inhalation solution for the relief of broncho-spasm in children with asthma. Another object of the present invention is to provide an inhaled solution of albuterol in reduced dose, previously measured, previously mixed, sterilized, previously packed for the relief of bronchospasm in patients from 2 to 12 years of age with asthma. It is yet another object of the present invention to provide an antibacterial preservative-free albuterol inhalation solution to alleviate bronchospasm in a pediatric patient with asthma. A further object of the present invention is to provide a method for administering an albuterol inhalation formulation to alleviate the bronchospasm associated with pediatric asthma. A further object of the present invention is to provide a device or system for the relief of broncho-spasm in a pediatric patient with asthma. A further object of the present invention is to provide a method for making an inhalation solution for the relief of broncho-spasm in a pediatric patient with asthma. Another object of the present invention includes a device for use in the relief of bronchospasm in a pediatric patient with asthma.

Other objects, features and advantages of the present invention will be apparent to those ordinarily skilled in the art in view of the following detailed description of the present invention and the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES Figures 1 to 4, describe a non-limiting example of administration of the inhalation solution of the present invention by a nebulizer. Figure 5 represents a non-limiting example of a previously packaged unified equipment or system of the present invention. Figure 6 describes a non-limiting example of one or more pre-filled packages comprising the inhalation system of the present invention. Figure 7 describes a non-limiting example of a label used in the present invention. Figure 8 shows the% change from the pre-dose of FEVi in the population to be treated (day 1); and Figure 9 shows the% change from the pre-dose of FEV-i in the population to be treated (day 28).

DETAILED DESCRIPTION OF THE INVENTION Albuterol The present invention is based on the bronchodilating effects of albuterol to provide relief of symptoms associated with COPD. As used in the present description, the term "albuterol" includes, but is not limited to, any form of albuterol, which has the ability to produce a desired bronchodilation effect in patients, including, but not limited to, all the tautomeric forms, enantiomeric forms, stereoisomers, anhydrides, acid addition salts, base salts, soluble-solvent compounds, analogs and albuterol derivatives. In the present invention, acceptable salts of albuterol may include, but are not limited to, hydrochloride, sulfate, maleate, tartrate, citrate, and the like. These and other acceptable salts are described in the U.S. Patent. No. 3,644,353, which is incorporated herein by reference in its entirety. In the present description, the preferred albuterol salt is sulfate. In an alternative embodiment, the inhalation solution of the present invention comprises the racemic albuterol sulfate salt. Albuterol sulfate is a relatively selective beta-2-adrenergic bronchodilator with an empirical formula C13H21NO3. The chemical name for albuterol sulfate is a1 - [(tert-butylamine) methyl] -4-hydroxy-m-xylene-a, a'-diol (2: 1) (salt) sulfate, and its structure Chemistry is established as follows: present invention, albuterol can be provided in a variety of pharmaceutically acceptable carriers, including, but not limited to, water or other aqueous solutions comprising a pharmaceutically acceptable amount of an osmotic agent. In another alternative embodiment, the inhalation solution of the present invention comprises a therapeutically effective pediatric amount of albuterol. As used in the present description, the phrase "therapeutically effective albuterol pediatric amount" means a safe and tolerable amount of albuterol for pediatric patients, as a basis for industry standards and / or regulatory standards. Said amount is sufficient to effectively induce bronchodilation and / or provide relief of bronchospasm in children. In the inhalation solution of the present invention, a therapeutically effective pediatric amount of albuterol may include from about 0.63 mg to about 1.25 mg of albuterol. In this case, the potency of albuterol is equivalent to from about 0.75 mg to about 1.50 mg of albuterol sulfate, respectively. In an alternative embodiment, a therapeutically effective amount of albuterol pediatric may include from about 0.63 to about 1.25 mg of albuterol. In another alternative embodiment, said pediatric amount does not comprise more than about 1.25 mg of albuterol, or comprises 1.25 mg of albuterol or less. In another alternative embodiment of the present invention, a therapeutically effective pediatric amount of albuterol may include from about 0.80 mg to about 1.90 mg of albuterol, which includes the following intermediate amounts of albuterol: from about 0.08 mg to about 0.20 mg; from about 0.21 mg to about 0.50 mg; from about 0.51 mg to about 0.60 mg; from about 0.61 mg to about 0.70 mg; from about 0.71 mg to about 0.80 mg; from about 0.81 mg to about 0.90 mg; from about 0.91 mg to about 1.00 mg; from about 1.0 mg to about 1.05 mg; from about 1.06 mg to about 1.10 mg; from about 1.1 mg to about 1.15 mg; from about 1.16 mg to about 1.0 mg; from about 1.2 mg to about 1.25 mg; from about 1.26 mg to about 1.30 mg; from about 1.31 mg to about 1.35 mg; from about 1.36 mg to about 1.40 mg; from about 1.41 mg to about 1.45 mg; from about 1.46 mg to about 1.50 mg; from about 1.51 mg to about 1.55 mg; from about 1.5 mg to about 1.6 mg; from about 1.61 mg to about 1.65 mg; from about 1.66 mg to about 1.70 mg; from about 1.71 mg to about 1.75 mg; from about 1.76 mg to about 1.80 mg; from about 1.81 mg to about 1.85 mg; from about 1.86 mg to about 1.90 mg. In another alternative embodiment of the present invention, a therapeutically effective pediatric amount of albuterol may include from about 0.1 mg to about 2.5 mg of albuterol sulfate, which includes the following intermediate amounts of albuterol sulfate: from about 0.1 mg to about 0.2 mg; from about 0.3 mg to about 0.4 mg; from about 0.5 mg to about 0.6 mg; from about 0.7 mg to about 0.8 mg; from about 0.9 mg to about 1.00 mg; from about 1.01 mg to about 1.0 mg; from about 1.21 mg to about 1.40 mg; from about 1.41 mg to about 1.60 mg; from about 1.61 mg to about 1.80 mg; from about 1.81 mg to about 2.00 mg; from about 2.01 mg to about 2.20 mg; from about 2.21 mg to about 2.40 mg; from about 2.41 mg to about 2.50 mg. In another alternative embodiment of the present invention, a therapeutically effective amount of albuterol pediatric can include from about 0.002% by weight to about 0.075% by weight of albuterol, which include the following intermediate amounts of albuterol: from about 0.002% by weight to about 0.010% by weight; from about 0.01 1% by weight to about 0.020% by weight; from about 0.021% by weight to about 0.030% by weight; from about 0.031% by weight to about 0.040% by weight; from about 0.041% by weight to about 0.050% by weight; from about 0.051% by weight to about 0.060% by weight; from about 0.061% by weight to about 0.070% by weight; from about 0.071% by weight to about 0.075% by weight. In yet another alternative embodiment of the present invention, a therapeutically effective pediatric amount of albuterol may include from about 0.003% by weight to about 0.1% by weight of albuterol sulfate in solution, which includes the following intermediate amounts: from about 0.003% by weight up to approximately 0.010% by weight; from about 0.011% by weight to about 0.020% by weight; from about 0.021% by weight to about 0.030% by weight; from about 0.031% by weight to about 0.040% by weight; from about 0.041% by weight to about 0.050% by weight; from about 0.051% by weight to about 0.060% by weight; from about 0.061% by weight to about 0.070% by weight; from about 0.071% by weight to about 0.080% by weight; from about 0.081% by weight to about 0.090% by weight; from about 0.091% by weight to about 0.10% by weight. Most pharmaceutical inhalation solutions contain an antibacterial preservative, such as BAC or EDTA. One problem with solutions containing BAC is that BAC can produce paradoxical bronchoconstriction if the solution is administered repeatedly at short intervals. Another problem is that, when inhaled by an asthmatic patient, BAC can cause dose-dependent bronchoconstriction. The inhalation solution of the present invention can be provided with BAC, therefore it makes it more suitable for pediatric patients, especially in an emergency situation where the inhalation solution is administered repeatedly over a short period of time. Also, administering a BAC-free inhalation solution to a pediatric patient reduces the concomitant responsibility for the adverse effects associated with BAC. It also reduces the toxicity and other side effects associated with BAC. The inhalation solution of the present invention can also be provided in sterilized dose unit treatments, thereby eliminating the need to include BAC in the solution. Additionally, as shown in Table 1, in its sterilized form, the formulation of the present invention (which comprises a therapeutically effective pediatric amount of albuterol) provides a stable pediatric inhalation solution, such that the solution can be stored (for example, on a shelf) for long periods of time.

TABLE 1 STABILITY DATA * as a percentage by label requirement (0.021% by weight and 0.042% by weight of albuterol, respectively).

Another benefit of a sterilized inhalation solution is that it reduces the possibility of introducing contaminants into the patient when administered to the patient, thereby reducing the possibility of opportunistic infection in the patient. As stated above, the compositions provided in the present disclosure are stable. For example, the compositions provided in the present disclosure are stored at a temperature between about 15 ° C and about 30 ° C, and remain stable for a relatively long period of time. In one embodiment, the compositions are stored at a temperature of 25 ° C. In another embodiment, the stability of the compositions provided in the present disclosure may contain more than 80%, 85%, 90% or 95% of the initial amount of the active ingredient, for example, albuterol at a certain temperature over a period of time long. Accordingly, for example, a composition that is stable for 30 days at a temperature of 25 ° C, could have more than 80%, 85%, 90% or 95% of the initial amount of the active ingredient present in the composition at 30 days continuing with a storage at a temperature of 25 ° C. In another embodiment, the compositions of the present disclosure are stable during long-term storage, wherein the compositions are suitable for administration to a subject in need thereof when they have been stored for a length of time (i.e. shelving life). ) for a period greater than 1, 2 or 3 years at a temperature of 25 ° C. In other embodiments of the present disclosure, using the Arrhenius kinetics, > 80%, > 85%, > 90% or > 95% it is estimated that, for example, the bronchodilating agent remains after said storage. Other indications for the stability of the present composition can be shown in terms of by-products or degradation products present over time, as shown in Table 2 below. TABLE 2 In one embodiment, the compositions produced in the present disclosure are at least substantially clear, based on the color measurement tests established by the America Public Health Association ("APHA"). For example, the APHA color results for compositions of the present description up to 24 months at a temperature of 25 ° C may be in the range of less than 10 units, or preferably from 0 to 5 units, more preferably 0 units based on the APHA standards. In one embodiment, the process of the present invention provides compositions having an albuterol content of about 0.021% by weight or 0.042% by weight per bottle. In another alternative embodiment, the process of the present invention provides compositions having an albuterol content of from about 0.0197% to about 0.218% weight per volume, from about 0.0201% to about 0.0214% by weight per volume, from about 0.0394% up to approximately 0.0436% by weight per volume and from approximately 0.0403% to approximately 0.0428% by weight per volume per bottle. In yet another alternative embodiment, the process of the present invention provides an average fill volume from about 2.80 ml to about 3.30 ml in each flask. In another alternative embodiment, the process of the present invention provides compositions that may contain minimal amounts of contaminants including, but not limited to, the following: TABLE 3 In another alternative embodiment, said compositions may also contain minimal amounts of subject particle, which includes, but is not limited to the following: an NMT from about 1000 to 5000, preferably an NMT from about 3800 particles / flask >; 2 mm; an NMT from about 10 to 100, preferably about 80 particles / flask > 10 mcm; or an NMT of from about 1 to about 5 particles, preferably NMT of about 3 particles / flask > 25 mcm. Adherence to asthma medication therapy and prevention of asthma medication error are considerable problems. These problems can be significantly reduced by providing asthmatic patients with a pre-packaged amount of previously measured, pre-packaged albuterol. By providing albuterol in this form, asthma therapy is made simple because it is conveniently increased and eliminates confusion in preparing the proper dosage. These advantages are especially significant in the treatment of pediatric asthma, where treatments are often presented in multiple dosage units and must be diluted to specific concentrations suitable for treating a pediatric patient. This has several problems. For example, treatments for asthma that require administration of a single dose unit of multiple dosage units sometimes lack instructions for proper mixing or dilution, or instructions for the preparation and use of asthma treatment can be difficult. to follow or you can easily lose. Even more important is the dilution or casual mixing of asthma medications, which can result in the administration of the wrong dose. This could be especially harmful for pediatric patients, who are often less tolerant of high dosages of albuterol. Improper mixing can also result in treatment failures such that additional medical attention is required, thereby increasing the time, expense, and personnel costs associated with the therapy. The present invention overcomes the aforementioned problems by providing therapeutically effective pediatric amounts of albuterol in a unit of previously measured, previously mixed, pre-packaged doses and / or unit dose amounts. In one embodiment, the present invention comprises one or more containers previously filled. The one or more containers, each comprising a single dose unit of an aqueous solution comprising a therapeutically effective pediatric amount of albuterol for the relief of bronchospasm associated with pediatric asthma. Providing the inhalation solution in such form eliminates the need to dilute or mix asthma medications to obtain correct dosages for treatment. Also, no special pharmaceutical composition is required and the possibilities of errors in medication are reduced. Additionally, there is a lower risk of cross-contamination, and less wastage of the medication when an inhalation solution is provided in a pre-mixed form, ready to be used. Other features of the present invention include improved user compliance and quality of life compared to conventional treatments for relieving bronchospasm in children.

Although the level of compliance with any asthma treatment depends in part on the motivation and skill of the individual performing the treatment distribution, however, compliance can be improved by factors that can be controlled, such as ease with the which treatment can be administered, as well as the convenience of receiving the treatment. The present invention provides a suitable, rapid and reliable treatment to alleviate bronchospasm in children, and clearly represents an improvement over traditional asthma treatments. Also, the present invention is designed to facilitate compliance to the user by providing one or more dispensing containers comprising a previously measured, pre-mixed inhalation solution comprising a single dose unit of a therapeutically effective amount of albuterol, for the relief of broncho-spasm in children. Said containers can be used in a relief method of said bronchospasm, or the containers can be incorporated in a system and / or equipment to treat it. In an alternate mode! iva, the formulation of the present invention is a pre-measured, previously measured, BAC-free sterilized inhalation solution comprising a single dose unit of a therapeutically effective pediatric amount of albuterol in a single container. Each dose container contains either 0.75 mg / 3 ml of albuterol sulfate (equivalent to 0.63 mg of albuterol) or 1.50 mg / 3 ml of albuterol sulfate (equivalent to 1.25 mg of albuterol) in one dose. sterilized aqueous solution. Sodium chloride can be added to adjust the isotonicity of the solution and sulfuric acid can be added to adjust the pH of the solution to about 3.5, the inhalation solution of the present invention may or may not include a chelating agent, such as EDTA . In another alternative embodiment, the inhalation solution of the present invention can be provided as a 3 ml sterilized BAC-free nebulizer solution, comprising from about 0.75 mg / 3 ml to about 1.50 mg / 3 ml of sodium sulfate. albuterol (equivalent to approximately 0.63 mg to approximately 1.25 mg of albuterol, respectively). The nebulizer solution is contained in a low density polyethylene container (LDPE) dose unit. Each dose unit container can be placed in a foil pouch, and each foil pouch can contain 5 or more dose unit bins. Each aluminum foil bag containing the container of the dose unit can be placed on a cardboard base. The present invention provides an albuterol inhalation solution for alleviating bronchospasm in pediatric patients with asthma, including, but not limited to, allergic (extrinsic) asthma, non-allergic (intrinsic) asthma, occupational asthma, and susceptible asthma to aspirin. The present invention also provides an albuterol inhalation solution for relieving bronchospasm associated with different types of pediatric asthma, including, but not limited to, severe persistent asthma, persistent asthma, a pediatric patient after the onset of bronchospasm. to reduce the aspiration difficulties resulting from asthma. In another embodiment, albuterol can be administered prophylactically, that is, to prevent or reduce the extent of bronchospasm. The amount of albuterol that will be administered will be determined on an individual basis, and will be based, at least in part, on consideration of the patient's size, the severity of the symptoms to be treated and the results sought. The actual dose (amount of albuterol administered at one exposure) and the number of administrations per day, will depend on the mode of administration, such as an inhaler, nebulizer or oral administration. For example, can be provided from about 0.63 mg to about 1.25 mg of albuterol, by nebulization one or more times a day could be adequate to produce the desired bronchodilation effect in most children. In an alternative embodiment, the inhalation solution of the present invention provides relief of bronchospasm in patients 2 to 12 years of age. For example, a dose unit of 0.63 mg of albuterol inhalation solution is effective for children 10 years of age and younger, children weighing <40 kg or children with less severe asthma. A dose unit of 1.25 mg of albuterol is effective for prolonged use in children 1 1 to 12 years of age, children who weigh > 40 kg or in children with more severe asthma.

Additionally, the albuterol inhalation solution of the present invention can be administered together with one or more drugs. For example, an anti-asthmatic drug, such as theophylline or terbutaline, or an antihistamine or analgesic, such as aspirin, acetaminophen or ibuprofen, may be administered with or at a dose in close proximity to administration of a therapeutically effective pediatric amount of albuterol. The albuterol and the one or more drugs can be administered in a formulation or as two separate entities. In accordance with the present invention, a therapeutically effective pediatric amount of albuterol, alone or in combination with another drug (s), can be administered to a pediatric individual periodically as necessary to reduce the symptoms of asthma. In an alternative embodiment of the present invention, relief of severe persistent asthma may include the administration of a therapeutically effective pediatric amount of albuterol to rapidly relieve symptoms and a high dose of inhaled corticosteroids using a spacer or holding chamber with a mask . If necessary, oral corticosteroids (2mg / kg / day) can be administered. The oral corticosteroid could be reduced to the lowest daily dose or alternating days that stabilizes the symptoms. For moderate persistent asthma, treatment may include the administration of therapeutically effective pediatric amounts of albuterol for rapid relief of symptoms and an inhaled corticosteroid at a mid-level dose, administered using a spacer or maintenance chamber with a mask. As symptom control is achieved, the dose of the inhaled corticosteroid can be decreased and both inhaled nedocromil and theophylline can be added. For mild persistent asthma, the treatment may include the administration of a pharmaceutically acceptable pediatric amount (s) of the present formulation for rapid relief of symptoms and daily anti-inflammatory medication, such as a lower dose inhaled corticosteroid using a camera spacer or maintenance with a mask or cromolina test by nebulizer or nedocromili using MDI. For mild intermittent asthma, apart from the administration of a therapeutically effective pediatric amount of albuterol, no daily drug therapy is ordinarily required. In another alternative embodiment, the inhalation solution of the present invention can be administered by a nebulizer, wherein said nebulizer includes, but is not limited to, a pressure nebulizer, an ultrasonic nebulizer and an aspiration activated nebulizer. Preferably, the nebulizer is a pressure nebulizer connected to an air compressor with a suitable air flow. The nebulizer is equipped with a suitable mouthpiece or mask. In an alternative embodiment, the system and / or equipment of the present invention comprises an inhalation solution comprising a therapeutically effective pediatric amount of albuterol in a pre-packaged, previously measured, previously mixed and / or single dose unit form for the relief of broncho-spasm in children. The inhalation solution can be sterilized and / or free of antibacterial preservatives. In another embodiment, the present invention provides a system and / or equipment for organizing and storing one or more pre-filled distribution containers, wherein each container comprises a previously measured, pre-mixed inhalation solution comprising a single dose unit in a therapeutically effective amount of albuterol. Said system and / or equipment can provide said containers in a pre-packaged form. The one or more containers may be comprised of plastic including, but not limited to, semi-permeable plastic, such as, for example, LDPE. The container may also comprise a Twist-Flex ™ upper part, said upper part comprising an easy-grip tongue-type handle, in such a way that the container can be opened, for example by screwing the tongue by hand. The upper Twist-Flex ™ is advantageous in that it allows the solution to be easily distributed, prevents spillage and eliminates the need to open the container by cutting the top or in a similar manner, thereby reducing cross-contamination. One or more of the semi-permeable single dose unit containers can be placed in a sealed aluminum foil pouch, such that the pouch provides a protective barrier against environmental contaminants and light. Said barrier improves shelf life and stability of the inhalation solution.

In another alternative embodiment, the present invention comprises a previously packaged inhalation and / or equipment system, suitable for pediatric patients suffering from asthma. Said system previously and / or packaged equipment comprises: (a) one or more unit of single doses of a therapeutically effective pediatric amount of albuterol; (b) administration instructions for the use of said dosage unit as a treatment for pediatric asthma; and (c) a distribution container previously filled with one or more than one dose unit of albuterol. In another alternative embodiment, the pre-packaged inhalation system or equipment of the present invention provides one or more pre-measured, pre-mixed single dose unit bottles comprising a therapeutically effective pediatric amount of albuterol for the relief of broncho-spasm associated with pediatric asthma, and instructions for using them. The pre-packaged inhalation system and / or equipment may be provided in any number of ways, including, but not limited to, a box containing one or more pre-packaged dose unit jars or a box containing individual packages or comprising bags comprising one or more dose unit bottles. For example, in Figure 5, a modality of a system and / or equipment previously packaged unified to alleviate bronchospasm in children is described. Specifically, Figure 5 illustrates a support, box, carton or container (10) package comprising one or more previously filled distribution containers, pre-packaged (21-25). Each container comprises a previously measured inhalation solution, previously mixed. The inhalation solution comprises a dosage unit of a therapeutically effective amount of albuterol pediatric to alleviate bronchospasm in a child suffering from asthma. The inhalation solution can be provided in a sterile form and / or in a free form of antibacterial preservatives. The support package, box, carton or container (10) can incorporate one or more labels (13) therein. One or more labels (13) may comprise indications (14) that indicate that the inhalation solution can be used to relieve bronchospasm in children. The label may also comprise indications (15), which provide instructions for using the inhalation solution to relieve bronchospasm in children. As used in the present description, the term "indications" includes, but is not limited to, drafting, photographs, drawings, symbols and / or forms. A non-limiting example of the indications that may appear on the one or more labels (13) is shown in Figure 7. The one or more labels may be placed on one or more surfaces of the support package, box, carton or container ( 10) or a separate sheet, or any combination thereof. The support package (10) can also incorporate a cover (16) to enclose the material packed therein.

The system and / or equipment of the present invention may also include a label and / or instructions designed to facilitate the user's understanding. For example, in one embodiment, a system and / or equipment of the present invention comprises the packaging material containing one or more pre-packaged vials comprising a previously measured, previously measured, sterilized dose unit of an inhalation solution that comprises a therapeutically effective amount of albuterol. The packaging material may additionally comprise a label indicating that each bottle can be used with each nebulizer treatment for the relief of bronchospasm associated with pediatric asthma. Such instructions may also include dosing instructions for each nebulizer treatment, as well as administration instructions, such as by the nebulizer. The instructions can be placed on one or more surfaces of the packaging material or the instructions can be provided on a separate sheet, or any combination thereof. In an alternative embodiment, the present invention is directed to a system and / or therapeutic equipment previously packaged to induce bronchodilation in a child suffering from asthma, wherein the previously packaged therapeutic system comprises: (a) one or more distribution containers; wherein the one or more containers have been pre-filled each with about 3 ml of a previously measured, previously measured aqueous solution of benzalkonium chloride-free, sterilized inhalation comprising a dose unit of a therapeutically effective pediatric amount of racemic albuterol; wherein the dosage of racemic albuterol is about 0.63 or about 1.25 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; (b) indications comprising the indication data of adverse reaction, dosage and administration pertaining to the inhalation solution in each of the one or more containers; (c) wherein the indication data comprises data that the inhalation solution in each of the one or more containers is indicated for the relief of broncho-spasm in patients from 2 to 12 years of age with asthma; and (d) wherein the adverse reaction data comprises data indicating that otitis media and skin appendix infection can occur after administration of the inhalation solution in the one or more containers. In another alternative embodiment, the previously packaged therapeutic system of the present invention comprises data that the dosage for patients aged 2 to 12 years is 0.63 mg or 1.25 mg of albuterol administered 3 to 4 times a day by nebulization for a period of time. 5 to 15 minutes. Also, the adverse reaction data may include a list of one or more previously printed adverse events that may occur after administration of the inhalation solution in each of the one or more containers, wherein the adverse events comprise asthma exacerbation, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea. In another alternative embodiment, the previously packaged therapeutic system and / or equipment is adapted to induce bronchodilation in children suffering from asthma, wherein the previously packaged therapeutic system may comprise: (a) one or more distribution containers; wherein the one or more containers are pre-filled each with 3 ml of a previously measured, previously mixed aqueous solution, free of benzalkonium chloride, stable, sterilized consisting essentially of a dose unit of a therapeutically effective pediatric amount of racemic albuterol; wherein the dosage of the racemic albuterol is about 0.63 or about 1.25 mg; wherein the racemic albuterol is in the form of an acid addition salt; wherein the acid addition salt is albuterol sulfate; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; (b) indications comprising adverse reaction indication data, and dosage and administration pertaining to the inhalation solution in each of the one or more containers; (c) wherein the indication data comprises data that the inhalation solution in each of the one or more containers is indicated for the relief of broncho-spasm in patients from 2 to 12 years of age with asthma; (d) wherein the adverse reaction data comprises a list of previously printed adverse events that may occur after administration of the inhalation solution in each of the one or more containers; where the adverse events include otitis media, infection of the appendix of the skin, exacerbation of asthma, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea; and (e) wherein the dosing and administration data comprise data that the dosage for patients from 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administered 3 to 4 times a day by nebulization over a period of time. 5 to 15 minutes. The present invention is also directed to a method for treating bronchospasm associated with pediatric asthma, wherein albuterol is administered as a dosage unit from about 0.63 mg to about 1.25 mg of albuterol. Said dose unit may be in the form of a nebulizer solution.

In an alternative embodiment, the method of the present invention comprises the step of administration to a patient of 2 to 12 years of age who needs an inhalation solution comprising a therapeutically effective pediatric amount of albuterol. Said solution may comprise from about 0.63 mg to about 1.25 mg of albuterol. Said solution can also be previously mixed, previously measured, free of antibacterial preservatives and / or sterilized. Said solution may also be in a single dose unit vial. In another alternative embodiment, the method of the present invention comprises the step of administering to a pediatric patient in need thereof, an inhalation solution comprising a therapeutically effective pediatric amount of albuterol. The inhalation solution is administered by a nebulizer, more preferably a pressure nebulizer connected to an air compressor with a suitable air flow. Still in another alternative modality, referring to the Figures 1 to 4, the method of the present invention comprises the steps of: (i) placing an inhalation solution comprising a therapeutically effective pediatric amount of albuterol (1) within a nebulizer vessel (2) the nebulizer can be switched on by joining to cylinders of compressed gas or an electrically driven compressor; (ii) using a "T" adapter (3) to adjust the glass lid (4) to a nozzle (5) or mask (6); (iii) extracting the inhalation solution (1) by the velocity of a pressurized gas and the fragmentation thereof in a spray; (iv) passing the spray through the nozzle (5) or mask (6) to the pediatric patient (7) suffering from bronchospasm; and (v) the patient continues to aspirate until no more mist forms in the nebulizer chamber (8). This can happen in a period of approximately 5 to 15 minutes. In an alternative embodiment, the common starting dose for patients of 2 to 12 years of age is approximately 1.25 mg or approximately 0.63 mg of albuterol administered 3 or 4 times a day, as needed by nebulization. To administer these amounts of albuterol, the entire contents of a dose unit bottle (eg, 1.5 mg / 3 ml or 0.75 mg / 3 ml albuterol sulfate) can be used by nebulization. Preferably, the flow rate of the nebulizer is adjusted to administer albuterol sulfate for a period of 5 to 15 minutes. Patients from 6 to 12 years of age with more severe asthma (starting point of FEVi less than 60% expected), weight > 40 kg or patients from 1 to 12 years of age can achieve a better initial response with approximately a dose of 1.25 mg. Additionally, in an alternative embodiment, the method of the present invention comprises the steps of: (i) preparing an inhalation solution comprising a therapeutically effective pediatric amount of the albuterol solution, diluting one or more solutions comprising the albuterol; and (ii) administering the inhalation solution to a patient in need thereof.

In another alternative embodiment, the present invention is directed to a method for inducing bronchodilation in a child suffering from asthma, wherein said method comprises the steps of: (a) providing the prescribing child or person with a therapeutic system previously package comprising: one or more distribution containers; wherein the one or more containers are each pre-filled with approximately 3 ml of a previously measured, previously sterilized, stable, benzylconium-free, sterilized aqueous inhalation solution comprising a dosage unit of a therapeutically effective pediatric amount of racemic albuterol; wherein the dosage of racemic albuterol is about 0.63 or about 1.25 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; (b) provide the child or person performing the prescription of the previously packaged therapeutic system with indication, adverse reaction, dosage and administration data pertaining to the inhalation solution in each of the one or more containers; (c) wherein the indication data inform the patient or prescribing person that the inhalation solution in each of the one or more containers is indicated for the relief of bronchospasm in patients from 2 to 12 years of age with asthma; and (d) wherein the adverse reaction data inform the patient or person making the prescription that otitis media and skin appendix infection may occur after the administration of the inhalation solution in the one or more containers. In another alternative modality, dosing and administration data inform the patient or prescribing person that the dosage for children 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administered 3 to 4 times a day by Misting for a period of 5 to 15 minutes. Also, the adverse reaction data may include a list of one or more previously printed adverse events that may occur after the administration of the inhalation solution in each of the one or more containers, wherein the adverse events comprise exacerbation of the asthma, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea. In another embodiment, the method of the present invention is directed to induce bronchodilation in a child suffering from asthma. Said method may comprise the step of: (a) providing the prescribing child or person with a previously packaged therapeutic system comprising: one or more distribution containers; wherein the one or more containers are each pre-filled with approximately 3 ml of a previously sterilized, stable, benzálconium-free, pre-mixed, sterilized, aqueous inhalation solution consisting essentially of a dose unit of a pediatric amount therapeutically Effective of racemic albuterol; wherein the dosage of racemic albuterol is from about 0.63 to about 1.25 mg; wherein the racemic albuterol is in the form of an acid addition salt; wherein the acid addition salt is albuterol sulfate; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life. (b) providing the child or person performing the prescription of the previously packaged therapeutic system with data indicating adverse reaction, dosage and administration pertaining to the inhalation solution in each of the one or more containers; (c) wherein the indication data inform the patient or prescribing person that the inhalation solution in each of the one or more containers is indicated for the relief of bronchospasm in patients from 2 to 12 years of age with asthma; (d) where the adverse reaction data inform the patient or person making the prescription that otitis media may occur, infection of the appendix of the skin, exacerbation of asthma, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine , chest pain, bronchitis or nausea after administration of the inhalation solution in the one or more containers; and (e) wherein the dosing and administration data comprise data informing the patient or person making the prescription that the dosage for patients of 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administered from 3 to 4 times a day by nebulization for a period of 5 to 15 minutes. The present invention also provides a method for making a sterilized, previously mixed, previously measured inhalation solution and / or a BAC-free solution comprising a single dose unit of a therapeutically effective pediatric amount of albuterol. In said embodiment, the method of the present invention comprises one or more of the following steps; (i) adding at least a therapeutically effective pediatric amount of albuterol in a vehicle, such as water; (ii) optionally, sterilize the solution and seal the container. An osmotic adjustment agent can be added to adjust the isotonicity of the solution. In one embodiment of the present invention, the solution of the present invention is isotonic. Isotonicity can be achieved by adding an osmotic adjustment agent to adjust the isotonicity of the solution from about 280 to about 320 mOsm / kg. Additionally, an acid (eg, sulfuric acid) can be added to adjust the pH of the solution to a level within the range of from about 3.0 to about 4.0, preferably from about 3.5. In another embodiment, a method for making an inhalation solution of the present invention comprises one or more of the following steps: (i) adding at least a therapeutically effective pediatric amount of albuterol in a vehicle such as water; (ii) placing the mixture in a container and sterilizing the mixture by steam sterilization, or any other sterilization means known in the art. Placing each mixture inside a jar, and then pack it, store it and / or use it directly. At this point, the resulting mixture is stable and after sterilization, it can be distributed, if necessary, into multiple mixtures, each containing a dose unit of a therapeutically effective amount of albuterol pediatric. Osmotic adjustment agents, which may be used, include, but are not limited to, sodium chloride, potassium chloride, zinc chloride, calcium chloride, and mixtures thereof. Other osmotic adjusting agents may also include, but are not limited to, mannityl, glycerol and dextrose and mixtures thereof. In an alternative embodiment, the present invention may comprise from about 0.4 to about 1.0 percent by weight of ionic salt. Preferably, the present invention comprises about 0.9 percent by weight of an osmotic adjusting agent.

In an alternative embodiment, the inhalation solution of the present invention can be prepared in the following manner: (i) by adjusting a high density polyethylene (HDPE) or stainless steel formulation tank with a bottom conduit and a recirculation system peristaltic (for HDPE) or triple mixer (for stainless steel) to mix; (ii) fill the tank with approximately 90% of the required amount of USP purified water at a temperature between 18 ° C and 25 ° C; while mixing, (iii) adding sulfuric acid, sodium chloride USP, and at least a therapeutically effective pediatric amount of albuterol sulfate USP to the tank; (iv) continue mixing until all the chemical components have dissolved; (v) add USP purified water to adjust the final volume, if necessary, thus producing a mixture of albuterol. From the formulation tank, the albuterol mixture is pumped through the sanitary administration lines directly into a forming-filling-sealing machine (FFS). The albuterol mixture is passed through a 0.2 micron sterilizer cartridge filter, to the filling nozzles within a sterilized air bath compartment and subsequently into vials formed of low density polyethylene (LDPE). The albuterol mixture is sterile filled into bottles, such that each bottle contains a single dose unit of a therapeutically effective amount of albuterol. The filled bottles are then sealed. The machine can form, fill and seal the bottles in a continuous operation under aseptic conditions, thus producing a sterilized product. For example, the cards of five full bottles (Figure 6) are wrapped in a foil bag of protective foil using an automatic wrapping machine. Five or twenty of these bags can then be packed in a cardboard base, thus forming a previously packaged therapeutic system to relieve bronchospasm in children suffering from asthma. A label and the appropriate instructions can be added to the cardboard base. The present invention is also directed to a method for forming a dose unit nebulizer solution comprising the step of: (i) preparing a mixture containing a therapeutically effective pediatric amount of albuterol in a pharmaceutically acceptable carrier. In an alternative embodiment, the present invention also comprises a device for use in the relief of bronchospasm associated with pediatric asthma. Said device may take the form of a label, written instructions or any other form of incorporating the indications therein. The device may comprise indications, which indicate that a patient suffering from broncho-spasm can be treated with at least one previously packaged, sterilized, previously mixed inhalation solution, previously measured and / or free of antibacterial preservatives comprising a unit of a therapeutically effective pediatric amount of albuterol in a single bottle. The inhalation solution is suitable for nebulization in a nebulizer. The device also comprises indications, which provide instructions for using the inhalation solution to relieve said bronchospasm in the patient.

EXAMPLES The patients were randomized to receive a nebulizer solution comprising either 0.63 mg / 3 ml or 1.25 mg / 3 ml of albuterol sulfate, or a placebo. The inhalation solution was administered by means of a Pari LC Plus ™ nebulizer and a Pari PRONEB ™ compressor. Both products are commercially available. In that study, the ages of children aged 6 to 12 years were randomized to receive 1 of the following three treatments twice a day (TD) for 4 weeks, each in a volume of 3.0 mL: (1) 1.25 mg of albuterol sulfate inhalation solution; (2) 0.63 mg of albuterol sulfate inhalation solution; or (3) placebo (saline). Each patient was provided with a PARI LC PLUS ™ nebulizer powered by a personal compressor, from Pari Respirator Equipment Inc., Richmond, VA, during the study. A selected visit was followed by a 2-week administration of placebo-phase testing to confirm the need for regular symptomatic beta-agonist therapy and to provide patients with experience with daily and peak flow measurements, as well as for demonstrate compliance. The study period of 4 weeks started with the initial dose, which would be taken in the morning, administered at the study site. Pulmonary function tests were performed before the dose and pulmonary function tests 30 minutes after the end of the nebulization and every hour thereafter for 6 hours. After 11 days, patients returned to exchange study medication and pulmonary function tests and daily tests before and 30 minutes after the morning dosing. After completing the 28 days of treatment, patients returned to the test site for a repeat assessment at 6 hours of safety and efficacy after the administration of the study medication. The daily cards were used to record asthma symptoms, nighttime awakenings, peak flow measurements, use of albuterol supplementation, change in medication and adverse events. The safety profiles of each dose unit and placebo were determined by the collection of vital signs (heart rate, blood pressure, respiration index and body temperature) as well as electrocardiograms.

PATIENTS A total of 349 children (220 boys and 129 girls) were initially randomized, and 288 finished the 4-week double-blind treatment period. The demographic characteristics and other starting points could be compared between the three treatment groups. In order to be eligible for registration, patients had to meet the criteria described in Table 3 below.

TABLE 5 INCLUSION / EXCLUSION CRITERIA Design element Description Criteria for inclusion • Documented history (26 months) of moderately severe persistent asthma confirmed by a physician and requiring daily medication for asthma. • Generally good health apart from asthma • FEV, between 50% and 80% of the expected values at the starting point and at the start of the double blind treatment phase • At least 15% reversibility in FEVi followed by administration of inhaled nebulized albuterol at a screening visit • Symptomatic asthma requiring the use of beta agonists in at least 6 of the 14 observation days during the placebo test period. • Patient and caregiver's willingness to provide informed consent. Exclusion criteria • Severe asthma or any serious medical condition • Use of prescription medication for which, albuterol sulfate is contraindicated • Known hypersensitivity to albuterol or similar agents • Active lung disease other than bronchial asthma • Upper respiratory tract infection within 4 weeks of the start of the placebo phase • Any other chronic condition that could be interfered with the successful completion of the study or confused its interpretation • Acute use of corticosteroids or other treatments, which may interfere with the study within 4 Selection visit weeks • Inability or unwillingness to perform the requirements of the protocol INTERVENTIONS Patients who met the inclusion criteria and prescribed asthma medications on a regular basis were allowed to continue those medications during the course of the study if the doses remained stable. Patients needed to stop their daily dose before each study visit and during the entire study session. After the patient finished the study session, the regularly scheduled dosage was started again for that day. All medication used to treat chronic conditions, including immunotherapy, had to be started at least 30 days before the start of the study, and the dosing regimen had to be stabilized by the initial visit. The racemic albuterol was administered using a chlorofluorocarbon MDI (CFC) or nebulizer were used on a necessary basis to rescue the medication.

EFFECTIVENESS OF RESULTS The endpoint of the main efficacy was the area under which the percentage change of FEV before the dose, against the time curve of the end of the initial visit (Day 1) and the end of the last visit (Day 28) ). Compared to placebo, both dose units of albuterol produced significant improvements in FEV, followed by both the initial dose and the dose provided at visit 4 after 4 weeks of TD treatment. The mean percentage changed from the starting point in the area under the 6-hour curve for FEVi for both active treatment regimens with placebo, this is shown in Figure 8 (for day 1) and Figure 9 (for day 28). ). The start of a 15% increase in FEV-i over the starting point for both doses of AccuNeb was observed at 30 minutes. The average time for the mentioned effect was approximately 30 to 60 minutes for both doses on the day and after 4 weeks of treatment. The average duration of the effect, as measured with a >; 15% increase in starting point in FEVi was approximately 2.5 hours for both doses on day 1 and approximately 2 hours for both doses after 4 weeks of treatment. In some patients, the duration of the effect was as long as 6 hours. The subgroup analysis was performed to determine if the overall efficacy of AccuNeb was consistent in all age groups, weight and severity of the disease. In all age groups, weight categories and disease severity groups, the dose of 1.25 mg provided a statistically significant improvement over placebo, both on Day 1 and on Day 28. However, with the lower dose of 0.63 mg, children from 1 to 12 years of age, children heavier than 40 kg and children with more severe disease (classified as in FEVi <60% of the predicted) did not have a statistically significant improvement in on the placebo for day 29. As a result, older children, heavier children or children with more severe disease may have a better response to the 1.25 mg dose.

SECURITY / TOLERANCE The adverse reaction information to the albuterol solution used in the study was derived from the 4-week controlled clinical trial described below. Adverse events were reported in > 1% of the patients who received the present solution, more frequently than the adverse events reported by patients who received the placebo, as shown in Table 6. In the study, a case of ST segment depression was presented in the group of treatment with 1.25 mg, but no clinically relevant laboratory abnormalities related to administration were observed.

TABLE 6 Reports of adverse events (Adverse events with an incidence of 0.1% of patients receiving the present albuterol solution and greater than placebo (expressed as% of the treatment group)) The Figures and inclusions of the present disclosure were presented for illustrative purposes only. These are not intended to limit the scope of the present invention. Additionally, it should be understood that various changes and modifications to the preferred embodiment currently described in the present description will be apparent to those skilled in the art. Said changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing the advantages that accompany it. Accordingly, it is intended that said changes and modifications be covered by the appended claims. Also, the present invention may suitably comprise, consist of or consist essentially of the elements described in the present disclosure. Additionally, the present invention described in the present description can be practiced in an adequate manner in the absence of any element which is not specifically described in the present description.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1. A pediatric inhalation solution comprising: a pre-measured previously mixed aqueous formulation comprising a single dose unit of a therapeutically effective amount of albuterol pediatric to induce bronchodilation or provide relief of bronchospasm in children suffering from asthma , wherein the amount of albuterol in the inhalation solution is in the range of from about 0.08 to about 1.90 mg; where the solution is provided in a single container. 2 - The pediatric inhalation solution according to claim 1, further characterized in that the inhalation solution is sterilized. 3. - The pediatric inhalation solution according to claim 1, further characterized in that the inhalation solution is free of an antibacterial preservative. 4. - The pediatric inhalation solution according to claim 3, further characterized in that the antibacterial preservative is benzalkonium chloride. 5. - The pediatric inhalation solution according to claim 1, further characterized in that the pH of the inhalation solution is within the range from about 3.0 to about 4.0. 6. - The pediatric inhalation solution according to claim 1, further characterized in that the pH of the solution of 5 inhalation is approximately 3.5. 7. - The pediatric inhalation solution according to claim 1, further characterized in that the albuterol is in the form of an acid addition salt thereof. 8. - The pediatric inhalation solution according to claim 10, further characterized in that the acid addition salt of albuterol is albuterol sulfate. 9. - The pediatric inhalation solution according to claim 1, further characterized in that the albuterol is in the form of a racemic mixture. 10. The pediatric inhalation solution according to claim 1, further characterized in that the amount of albuterol in the inhalation solution is within the range of from about 0.63 to about 1.25 mg. 1 1 .- The pediatric inhalation solution in accordance with the Claim 1, further characterized in that the amount of albuterol in the solution is about 0.63 mg or about 1.25 mg. 12. - The pediatric inhalation solution according to claim 1, further characterized in that the inhalation solution is suitable for nebulization in a nebulizer. 13. - The pediatric inhalation solution according to claim 12, further characterized in that said nebulizer is selected from the group consisting of a pressure nebulizer, ultrasonic nebuiizador or nebulizer activated by aspiration. 14. - A pediatric inhalation solution comprising: a pre-measured, previously measured sterilized aqueous formulation, free of benzalkonium chloride comprising a single dose unit of a therapeutically effective pediatric amount of albuterol to induce bronchodilation or provide bronchial relief -spasm in children suffering from asthma, where the amount of albuterol in the solution is within the range of approximately 0.63 mg to approximately 1.25 mg, where the solution is provided in a single container and where the inhalation solution It is suitable for nebulizer in a nebulizer. 15. The use of a pediatric inhalation solution according to claim 1 for preparing a medicament for inducing bronchodilation or providing relief of bronchospasm in a child suffering from asthma. 16. - The use as claimed in claim 15, wherein the pediatric inhalation solution is sterilized when administered to the child. 17. - The use as claimed in claim 15, in 5 where the pediatric inhalation solution is free of antibacterial preservative. 18. The use as claimed in claim 15, wherein the albuterol is in the form of an acid addition salt thereof. 19. The use as claimed in claim 18, wherein the addition salt of albuterol acid is albuterol sulfate. 20. The use as claimed in claim 15, wherein the albuterol is in the form of a racemic mixture. 21. - The use as claimed in claim 15, wherein the amount of albuterol in the inhalation solution is within the 15 range from about 0.63 to about 1.25 mg. 22. The use as claimed in claim 15, wherein the amount of albuterol in the inhalation solution is about 0.63 or about 1.25 mg. 23. - The use as claimed in claim 15, wherein the pediatric inhalation solution is administered to the child by nebulization. 24. - The use of the pediatric inhalation solution according to claim 14, for preparing a medicament for inducing bronchodilation or providing relief of bronchospasm in a child suffering from asthma, where it is administered by nebulization. 25. - The use of the pediatric inhalation solution according to claim 1, for preparing a medicament for inducing bronchodilation or providing relief of bronchospasm in a child suffering from asthma, wherein said medicament provides instructions for using the solution . 26. - A device for alleviating bronchospasm in a child suffering from asthma, said equipment comprising: (a) one or more containers, wherein said one or more containers each comprise a previously mixed aqueous inhalation solution, previously measurement comprising a single dose unit of a therapeutically effective pediatric amount of albuterol; wherein the amount of albuterol in the solution is in the range from about 0.08 mg to about 1.90 mg; wherein the solution is suitable for nebulization in a nebulizer. 27. - The equipment according to claim 26, further characterized in that the inhalation solution is sterilized 28. The equipment according to claim 26, further characterized in that the inhalation solution is antibacterial free preservative. 29. - The equipment according to claim 26, further characterized in that the amount of albuterol in the inhalation solution is in the range of about 0.63 mg to about 1.25 mg. 30. The equipment according to claim 26, further characterized in that the amount of albuterol in the inhalation solution is about 0.63 mg or about 1.25 mg. 31 The equipment according to claim 26, further characterized in that it additionally comprises a label which indicates that the inhalation solution can be used to alleviate bronchospasm in children suffering from asthma. 32. The equipment according to claim 26, further characterized in that it additionally comprises instructions for using the inhalation solution to relieve bronchospasm in children. 33. - The equipment according to claim 26, further characterized in that the one or more containers are packed in the same bag or box. 34. - The equipment according to claim 33, further characterized in that said containers comprise semi-permeable plastic and are packed in a foil bag. 35. - A team to treat bronchospasm in a child suffering from asthma, said equipment comprises: (a) one or more containers; wherein said one or more containers comprise a previously mixed sterilized aqueous inhalation solution, previously measured free of benzalkonium chloride for use in a nebulizer; wherein said inhalation solution comprises a single dose unit of a therapeutically effective pediatric amount of albuterol, wherein said pediatric amount is within the range of from about 0.63 mg to about 1.25 mg; (b) a label which indicates that the inhalation solution can be used to relieve bronchospasm in children suffering from asthma; and (c) instructions for using the inhalation solution to relieve said bronchospasm. 36. A previously packaged therapeutic system for alleviating bronchospasm in children suffering from asthma, said pre-packaged therapeutic system comprising packaging material, wherein said packaging material comprises: (a) one or more containers; wherein said one or more containers each comprise a premeasured, previously mixed, aqueous inhalation solution comprising a single dose unit of a therapeutically effective pediatric amount of albuterol; wherein said pediatric amount of albuterol is in the range of 0.08 mg to about 1.90 mg; being the right solution for nebulization in a nebulizer. 37. The therapeutic system previously packaged according to claim 36, further characterized in that said pediatric amount of albuterol is within the range of from about 0.63 to about 1.25 mg. 38. - The therapeutic system previously packaged according to claim 36, further characterized in that said pediatric amount of albuterol is approximately 0.63 mg or approximately 1.25 mg. 39 - The therapeutic system previously packaged according to claim 36, further characterized in that the inhalation solution in each of the one or more containers is sterilized. 40. The therapeutic system previously packaged according to claim 36, further characterized in that the inhalation solution in each of the one or more containers is free of antibacterial preservative. 41. - The therapeutic system previously packaged according to claim 36, further characterized in that said packaging material additionally comprises a label which indicates that the inhalation solution can be used to relieve bronchospasm in children. 42. The therapeutic system previously packaged according to claim 36, further characterized in that said packaging material comprises instructions for using the solution to relieve bronchospasm in children. 43. A previously packaged therapeutic system for alleviating bronchospasm in children suffering from asthma, said pre-packaged therapeutic system comprising a packaging material, wherein said packaging material comprises: (a) one or more containers; wherein the one or more containers each comprise a sterilized, previously mixed aqueous, previously measured antibacterial preservative-free inhalation solution for nebulization in a nebulizer; wherein the inhalation solution comprises a single dose unit of a therapeutically effective pediatric amount of albuterol, wherein the pediatric amount of albuterol is in the range of about 0.63 mg to about 1.25 mg; (b) a label indicating that the inhalation solution can be used to relieve bronchospasm in children; and (c) instructions for using the inhalation solution to relieve bronchospasm in children. 44. A method for preparing a previously mixed inhalation solution, previously measured to alleviate bronchospasm in children suffering from asthma; said method comprises the steps of: (a) placing a dosage unit of a therapeutically effective pediatric amount of albuterol in a pharmaceutically acceptable carrier, wherein the amount of albuterol in the vehicle is in the range of from about 0.08 mg to about 1 .90 mg; (b) provide the inhalation solution in a single container. 45. - The method according to claim 44, further characterized in that it further comprises the step of adding sulfuric acid to adjust the pH of the inhalation solution to a level that is within the range of from about 3.0 to about 4.0. 46. - The method according to claim 44, further characterized in that it further comprises the step of adding an osmotic agent to adjust the isotonicity of the inhalation solution; wherein the osmotic adjustment agent is selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride, and mixtures thereof. 47. The method according to claim 44, further characterized in that it further comprises the step of: (a) sterilizing the inhalation solution by passing it through a filter or by means of steam sterilization. 48. The method according to claim 44, further characterized in that it further comprises the step of adding sulfuric acid to adjust the pH of the inhalation solution to a level within the range of from about 3.0 to about 4.0. 49. - A method to prepare a previously mixed inhalation solution, previously measured to relieve bronchospasm in a child suffering from asthma; said method comprises the steps of: (a) placing a dose unit of a therapeutically effective pediatric amount of albuterol in a pharmaceutically acceptable carrier, wherein the amount of albuterol in the vehicle is within the range of from about 0.002 percent by weight to approximately 0.075 percent by weight; (b) provide the inhalation solution in a single container. 50. - A device to be used in the relief of bronchospasm in a child suffering from asthma, the device has indications; wherein the indications provide instructions for using a pre-mixed, previously measured inhalation solution comprising a single dose unit of a therapeutically effective amount of albuterol pediatric to alleviate said bronchospasm; wherein said pediatric amount of albuterol is in the range of from about 0.63 mg to about 1.25 mg of albuterol; wherein said solution is suitable for nebulization in a nebulizer. 51 - A previously packaged therapeutic system to induce bronchodilation in a child suffering from asthma, the previously packaged therapeutic system comprises: (a) one or more distribution containers; wherein the one or more containers are pre-filled each with about 3 ml of a pre-mixed, previously measured, sterilized, benzylated, free aqueous aqueous inhalation solution comprising a dose unit of a therapeutically effective pediatric amount of racemic albuterol; wherein the dosage of racemic albuterol is about 0.63 or about 1.25 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; (b) indications comprising adverse reaction indication, dosage and administration data pertaining to the inhalation solution in each of the one or more containers; (c) wherein the indication data comprises data that the inhalation solution in each of the one or more containers is indicated for the relief of bronchospasm in patients from 2 to 12 years of age with asthma; and (d) wherein the adverse reaction data comprises data indicating that otitis media and infection of the appendage of the skin can occur after administration of the inhalation solution in the one or more containers. 52. - The previously packaged therapeutic system according to claim 51, further characterized in that the racemic albuterol is in the form of an acid addition salt. 53. The therapeutic system previously packaged according to claim 52, further characterized in that the acid addition salt is albuterol sulfate. 54. The therapeutic system previously packaged according to claim 51, further characterized in that the dosing and administration data comprise data that the dosage for patients from 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administered 3 to 4 times a day by nebulization for a period of 5 to 15 minutes. 55. - The previously packaged inhalation solution according to claim 51, further characterized in that the adverse reaction data include a list of one or more previously printed adverse events that may occur after administration of the inhalation solution in each of the one or more containers; where the adverse events include, exacerbation of asthma, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea. 56. A previously packaged therapeutic system for inducing bronchodilation in a child suffering from asthma, characterized in that the previously packaged therapeutic system comprises: (a) one or more distribution containers; wherein the one or more containers are each pre-filled with approximately 3 ml of a previously measured, previously mixed, stable, sterilized, benzalkonium chloride-free aqueous inhalation solution consisting essentially of a therapeutically administered dose unit of a pediatric amount Effective of racemic albuterol; wherein the dosage of racemic albuterol is about 0.63 or about 1.25 mg; wherein the racemic albuterol is in the form of an acid addition salt; wherein the acid addition salt is albuterol sulfate; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; (b) the indications comprise data indicating the adverse reaction and dosage and administration pertaining to the inhalation solution in each of the one or more containers; (c) wherein the indication data comprises data that the inhalation solution in each of the one or more containers is indicated for the relief of bronchospasm in patients from 2 to 12 years of age with asthma; (d) wherein the adverse reaction data comprises a previously printed list of adverse events that may occur after the administration of inhalation solution in each of the one or more containers; where the adverse events include otitis media, infection of the appendix of the skin, exacerbation of asthma; allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea; and (e) wherein the dosing and administration data comprises data that the dosage for patients of 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administered 3 to 4 times a day by nebulization over a period of time. 5 to 15 minutes. 57.- The use of one or more distribution containers; wherein the one or more containers is pre-filled each with about 3 ml of a previously sterilized, stable, sterilized aqueous solution of previously measured benzalkonium chloride comprising a dosage unit of a therapeutically effective pediatric amount of racemic albuterol; wherein the dosage of racemic albuterol is about 0.63 or about 1.25 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; for preparing a medicament for inducing bronchodilation in a child suffering from asthma, wherein said previously packaged therapeutic system provides indication data of adverse reaction, dosage and administration, which belong to the inhalation solution in each of the one or more containers; wherein the indication data reports that the inhalation solution in each of the one or more containers is indicated for the relief of bronchospasm in children from 2 to 12 years of age with asthma; and wherein the adverse reaction data report that otitis media and infection of the appendix of the skin may occur after administration of the inhalation solution in the one or more containers. 58.- The use as claimed in claim 57, wherein the racemic albuterol is in the form of an acid addition salt. 59. The use as claimed in claim 58, wherein the acid addition salt of the racemic albuterol is albuterol sulfate. 60. - The use as claimed in claim 57, wherein the dosing and administration data report that the dosage for children 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administrable from 3 to 4 times a day by nebulization for a period of 5 to 15 minutes. 61. - The use as claimed in claim 57, wherein the adverse reaction data includes a list of one or more previously printed adverse events that may occur after providing the inhalation solution in each of the one or more containers; where adverse events include asthma exacerbation, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea. 62.- The use of a previously packaged therapeutic system comprising: one or more distribution containers; wherein the one or more containers are each pre-filled with approximately 3 ml of a previously measured, previously mixed, sterilized, stable, benzalkonium chloride-free aqueous inhalation solution consisting essentially of a therapeutically administered dose unit of a pediatric amount Effective of racemic albuterol; wherein the dosage of racemic albuterol is about 0.63 mg or about 1.25 mg; wherein the racemic albuterol is in the form of an acid addition salt; wherein the acid addition salt is albuterol sulfate; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a shelf life useful, to prepare a drug to induce bronchodilation in a child suffering from asthma, where it provides the person who performs the prescription of the therapeutic system previously packaged indication data, adverse reaction, dosage and administration pertaining to the inhalation solution in each of the one or more containers; wherein the indication data reports that the inhalation solution in each of the one or more containers is indicated for the relief of bronchospasm in patients from 2 to 12 years of age with asthma; where the adverse reaction data report that otitis media, skin appendix infection, asthma exacerbation, allergic reaction, gastroenteritis, flu disease, lymphadenopathy, urticaria, migraine, chest pain, bronchitis or nausea may occur after providing the inhalation solution in the one or more containers; and wherein the dosing and administration data comprise data that report that the dosage for children 2 to 12 years of age is 0.63 mg or 1.25 mg of albuterol administered 3 to 4 times a day by nebulization for a period of 5 hours. 15 minutes.