MXPA02011629A - Stable liquid and solid formulations. - Google Patents

Abstract

Stable pharmaceutical compositions containing non sedating antihistamines such as loratadine and a nasal decongestant such as pseudoephedrine sulfate and at least one pharmaceutically acceptable carrier, and stable pharmaceutical compositions containing non sedating antihistamines such as loratadine, nasal decongestants such as pseudoephedrine, and an expectorant such as Ambroxol and at least one pharmaceutically acceptable carrier which are stable to chemical and physical degradation and microbial contamination are disclosed.

Description

STABLE FORMULATIONS. LIQUID AND SOLID BACKGROUND OF THE INVENTION The present invention relates to stable, liquid and solid pharmaceutical compositions containing loratadine and a nasal decongestant and, optionally, containing an expectorant, and its use in the treatment of allergic and inflammatory conditions with cough and / or nasal congestion. Loratadine is a long-acting non-sedating antihistamine with selective peripheral reception of histamine H1 approved for the treatment of allergic reaction symptoms, for example, relief of nasal and non-nasal symptoms associated with seasonal allergic rhinitis or for the treatment of chronic idiopathic urticaria in human patients. Nasal decongestants such as phenylpropanolamine, pseudoephedrine and its pharmaceutically acceptable salts such as hydrogen chloride or acid addition salts of hydrogen sulfate are useful for the treatment of symptoms associated with allergic conditions such as seasonal allergic rhinitis or rhinitis. perennial allergic, as well as the symptoms associated with the common cold, including nasal congestion.

Mucolytic expectorants have been known in the art for some time. See Ambroxol, which is described in U.S. Patent No. 3,536,712. Despite being useful, neither non-sedating antihistamines nor nasal decongestants nor expectorants, in and of themselves, are capable of effectively treating the amount of symptoms that may be associated with respiratory tract diseases, such as bronchitis, broncho-spasm, seasonal allergic rhinitis, perennial allergic rhinitis, common colds, sinusitis and the concomitant symptoms associated with allergic asthma. The symptoms of such diseases may include sneezing, itchy nose, nasal congestion, redness of the eyes, tearing, itching of the ears or palate, and productive and nonproductive coughs. It would be highly desirable to provide a formulation of these known individual drugs which enhances their individual efficacy and improves their overall effectiveness. Syrup formulations are commonly used for the administration of drugs, particularly if the drugs are considered to be applied to pediatric patients. It has been discovered that the loratadine syrup formulations are unstable both chemically and physically and show a proliferation of microbial agents, such as mold, yeast and bacteria.

It would be desirable to provide solid and liquid pharmaceutical compositions containing loratadine and a nasal decongestant and, optionally, containing an expectorant that is chemically and physically stable and resistant to microbial contamination. It would also be desirable to provide liquid pharmaceutical compositions containing loratadine and a nasal decongestant and, optionally, containing an expectorant containing no sugar, eg, glucose or sucrose, and ethanol, and thus, be suitable for pediatric use.

BRIEF DESCRIPTION OF THE INVENTION The present invention provides liquid pharmaceutical compositions that are stable both chemically and physically and are protected from contamination by microbes after storage at room temperature for up to 36 months. The liquid pharmaceutical compositions of the present invention are suitable for pediatric use. The present invention provides a stable pharmaceutical composition comprising an effective amount of loratadine or a pharmaceutically acceptable salt thereof and an effective amount of a nasal decongestant or a pharmaceutically acceptable salt thereof, and, optionally, an effective amount of an expectorant or one of its acceptable salts for pharmaceutical use and at least one vehicle acceptable for pharmaceutical use. In a preferred embodiment, the present invention provides a stable liquid pharmaceutical composition, comprising an effective amount of loratadine or a pharmaceutically acceptable salt thereof and an effective amount of a nasal decongestant or a pharmaceutically acceptable salt thereof and at least one vehicle liquid acceptable for pharmaceutical use. In another preferred embodiment, the present invention further provides a liquid, stable pharmaceutical composition comprising an effective amount of loratadine or a pharmaceutically acceptable salt thereof and an effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof. and at least one liquid vehicle acceptable for pharmaceutical use. In another preferred embodiment, the present invention provides a liquid, stable pharmaceutical composition comprising an effective amount of loratadine or a pharmaceutically acceptable salt thereof and an effective amount of phenylpropanolamine or a pharmaceutically acceptable salt thereof and therefore less a liquid carrier acceptable for pharmaceutical use, and a combination of (1) a sweetener, (2) at least one solvent acceptable for pharmaceutical use, and (3) an amount of one system of buffer solution to maintain the pH as sufficient in the range of about 3.0 to about 5.0.

The present invention provides a pharmaceutical composition liquid, stable, comprising: Ingredient ma / ml Loratadine 0.50 Pseudoephedride sulphate 6.00 Glycerin 200.00 Propylene glycol 350.00 Sorbitol solution 70% 225.00 Saccharin sodium 0.40 Peanut flavoring No. 609 2.50 Citric acid, anhydride 0.64 Sodium citrate 0.02 Purified water is. To form 1.00? The present invention provides a pharmaceutical composition liquid, stable, comprising: Ingredient mg / ml Loratadine 0.50 Pseudoephedride sulphate 6.00 Glycerin 200.00 Propylene glycol 350.00 Sorbitol solution 70% 225.00 Saccharin sodium 0.40 Peanut flavoring No. 609 2.50 Citric acid, anhydride 0.64 Sodium citrate 0.02 Purified water is. To form 1.00 ml stable, liquid pharmaceutical compositions of the present invention, as the liquid pharmaceutical composition that is mentioned earlier, they are useful for the relief of associated symptoms with the congestion of the passage of the upper airways, which are associated with disorders such as perennial and seasonal allergic rhinitis and for relief associated with upper respiratory infections such as the common cold, including nasal congestion.

In another preferred embodiment, the present invention provides a stable pharmaceutical composition comprising an effective amount of loratadine or one of its acceptable salts for pharmaceutical use and a effective amount of nasal decongestant or one of its acceptable salts for pharmaceutical use and an effective amount of an expectorant or one of its salts acceptable for pharmaceutical use and at least one vehicle acceptable for pharmaceutical use. In another preferred embodiment, the present invention provides a stable pharmaceutical composition, oral, in tablets, comprising: Ingredients Name Concentration Basis% Variation (mg / tablet) Loratadine 5.00 Active Ambroxol Hydrochloride 30.00 Active Pseudoephedrine Sulphate 60.00 Active Lactose Anhydride 84.75 Filling ± 20 Corn starch 12.00 Disintegrant ± 20 Microcrystalline cellulose 16.75 Disintegrant ± 10 Colloidal silicon dioxide 0.75 Sliding ± 10 Magnesium stearate 0.75 Lubricant ± 10 Tablet weight 210.00 mg The oral tablets mentioned above are appropriate to administer twice per day.

In another preferred embodiment, the present invention provides a stable liquid pharmaceutical composition for oral administration, which includes: Ingredients Name Concentration Basis% Variation (mg / tablet) Loratadine 1.00 Active Ambroxol Hydrochloride 6.00 Active Pseudoephedrine Sulfate 12.00 Active Citric acid 0.40 Regulating Sun ± 10 Glycerin 150.00 Solvent ± 20 Propylene glycol 200.00 Solvent ± 20 Sodium saccharin 0.40 Sweetener ± 10 Sorbitol solution 70% 450.00 Solvent ± 20 Flavor 2.50 Flavor ± 10 Purified water is. Solvent ± 20 To form 1 1.0000 mmll The preferred flavor is the peach flavor No. 609, although it they can also use other flavors acceptable for pharmaceutical use. The oral solution described above is appropriate to administer twice a day.

In another embodiment of the invention, the present invention supplies an oral, stable pharmaceutical composition in tablets, which includes: Name of Ingredients Concentration Basis% V ariació (mg / tablet) Loratadine 3.33 Active Ambroxol Hydrochloride 30.00 Active Pseudoephedrine Sulfate 60.00 Active Lactose anhydride 76.42 Filling ± 20 Corn starch 12.00 Disintegrant ± 20 Microcrystalline cellulose 16.75 Disintegrant ± 10 Colloidal silicon dioxide 0.75 Sliding ± 10 Magnesium stearate 0.75 Lubricant ± 10 Weight of the tablet 200.00mg The oral tablets that were presented in the previous chart are appropriate to administer three times per day in a modality preferred, the present invention provides a pharmaceutical composition liquid, oral, stable, comprising: Name of the ingredients Concentration Basis% \ / ariaci (mg / tablet) Loratadine 0.66 Active Ambroxol Hydrochloride 6.00 Active Pseudoephedrine Sulfate 8.00 Active Citric acid 0.40 Regulating Sun ± 10 Glycerin 150.00 Solvent ± 20 Propylene glycol 200.00 Solvent ± 20 Sodium saccharin 0.40 Sweetener ± 10 Sorbitol solution 70% 448.00 Solvent ± 20 Flavor 2.50 Flavor ± 10 Purified water is. Solvent ± 20 To form 1.00 ml The above solution is appropriate to administer three times per day.

The preferred flavor is the peach flavor No 609, although they can also use other flavors acceptable for pharmaceutical use.

In this way, the present invention provides a new Three-way combination of a slow-release, non-sedating antihistamine as loratadine, and an expectorant and a mucolytic agent such as ambroxol, and a nasal decongestant such as pseudoephedrine in new, liquid and tablet preparations. These new Three-way combinations are indicated mainly for the release symptomatic of allergic respiratory conditions associated with non-productive cough, nasal congestion and the presence of mucus in the respiratory tract. These three-way pharmaceutical compositions of the present invention are also indicated in the treatment of those patients who show broncho-pulmonary conditions of allergic origin, or other aetiology associated with cough, in which the viscosity and adherence of the mucus is increased. , which obstructs the permeability of the airways. The main indications include, but are not limited to, allergic rhinitis associated with cough and nasal congestion, as well as acute, chronic, spasmodic and asthmatic bronchitis; bronchial asthma; bronchiectasis; sinusitis; otitis media; pneumonia, broncho-pneumonia; atelectasis due to mucosal obstruction; tracheotomy and as a pre- and post-prophylactic agent, especially in elderly patients in whom an allergic condition is suspected. The present invention provides the use of loratadine and a nasal decongestant for the preparation of a liquid pharmaceutical composition for the treatment of symptoms associated with allergic reactions in humans. The present invention provides the use of loratadine and a nasal decongestant for the preparation of a liquid pharmaceutical composition for the treatment of symptoms associated with allergic rhinitis and the common cold in a human.

The present invention provides the use of loratadine and a nasal decongestant for the preparation of a liquid pharmaceutical composition for the treatment of symptoms associated with allergic rhinitis and the common cold, including nasal congestion, sneezing, rhinorrhea, pruritus, and the tearing, in a human being. The present invention provides the use of a non-sedating antihistamine in combination with an expectorant and a nasal decongestant for the preparation of a medicament for the treatment of respiratory, allergic and inflammatory conditions, with cough, nasal congestion and the presence of mucus in the tract Respiratory, comprising an effective amount of a non-sedating antihistamine in combination with an effective amount of an expectorant, and an effective amount of a nasal decongestant. The nasal decongestant EJ is, preferably, pseudoephedrine or one of its acceptable salts for pharmaceutical use. The liquid pharmaceutical composition of two to three routes of the present invention is stable to contamination by microbes for periods of at least 4 months, preferably up to 36 months of storage at room temperature (25 ° C). The liquid pharmaceutical composition of two to three routes of the present invention is stable to the physical and chemical degradation of the active ingredients during periods of, at least, 4 months, with Preference, up to 36 months of storage at room temperature (25 ° C). The liquid pharmaceutical composition of two to three routes of the present invention is stable to contamination by microbes and physical and chemical degradation of the active ingredients for periods of at least 4 months, preferably up to 36 months of storage at temperature Environment (25 ° C). In a preferred embodiment, the liquid pharmaceutical compositions of the present invention substantially do not contain sugar, for example, glucose or sucrose, and ethanol, and thus, are suitable for pediatric use. DETAILED DESCRIPTION OF THE INVENTION We have discovered liquid pharmaceutical compositions containing loratadine and a nasal decongestant, preferably, pseudoephedrine with more preference pseudoephedrine sulfate, as active ingredients, which are stable to contamination by microbes, including, but not limited to, bacterial contamination, physical and chemical degradation of active ingredients, for periods of at least 4 months, preferably up to 36 months of storage at room temperature (25 ° C). As seen in Table 1, the preferred liquid pharmaceutical composition of Example 1 maintained a stable pH in the order of 3.3 to 4.3, and there was no change greater than 3% by weight in the original amounts of loratadine and pseudoephedrine sulfate after storage at room temperature for at least 4 months, and until 36 months. Similar behavior is expected for liquid and solid compositions containing loratadine, a nasal decongestant, such as pseudoephedrine, and a mucolytic agent such as ambroxol. In addition, there was no change in the physical appearance and color of the liquid pharmaceutical compositions of the present invention. The Antimicrobial Preservative Effectiveness Test ("APE") performed in the liquid pharmaceutical compositions of the present invention, as in Example 1 (See Table) demonstrated that the composition did not show contamination by microbes after storage at room temperature during, at least 4 months and up to 36 months. Nasal decongestants useful in the present invention include pseudoephedrine and phenylpropanolamine as a nasal decongestant and its pharmaceutically acceptable salts, especially hydrogen chloride and acid addition salts of sodium sulfate. The use of pseudoephedrine sulfate is preferred. The normally appropriate sweeteners include sugar, for example, glucose, as well as artificial sweeteners such as saccharin, for example, sodium saccharin, sorbitol, aspartame, sodium cyclamate, and their mixtures Preferably, a combination of two artificial sweeteners is used; more preferably, a combination of sodium saccharin and sorbitol is used. Sorbitol is usually a 70% by weight aqueous solution of sorbitol in purified water. In the preferred embodiments, the liquid pharmaceutical compositions of the present invention substantially do not contain sugar, for example, glucose or sucrose, and ethanol, and thus, are suitable for pediatric use. The term "substantially free of sugar and ethanol", as used herein, means that the pharmaceutical compositions of the present invention contain less than 1%, more preferably less than 0.5%, and even more preferably contain less than 0.1% in sugar weight, for example, glucose or sucrose, and ethanol, and thus, are suitable for pediatric use. Flavoring agents normally suitable include those flavoring agents approved for use in sweet pharmaceutical agents, foods, sweets and beverages. These flavoring agents impart flavor such as grape, cherry, citrus, peach, strawberry, chewing gum, mint and many others. The generally preferred pharmaceutically acceptable solvents include alcohols and glycols, especially propylene glycol, ethanol and giicerin. The liquid pharmaceutical compositions indicated for use pediatric should not contain substantially, and preferably, should not contain ethanol. The use of a combination of propylene glycol and glycerin is preferred. Normally suitable pH regulating systems include those capable of maintaining a pH in the range of 2.5 to 5.0, preferably about 2.9 to 4.3, more preferably 3.3 to 5.3. Preferred pH buffer systems include citric acid citrate sodium; and acetic acid / sodium acetate. The use of sodium citrate / citric acid as the pH regulating system is preferred. Normally, the liquid vehicle acceptable for pharmaceutical use is purified water. Although it is not desired to set a limit by means of any treatment, we believe that the unique combination of glycerin, propylene glycol, sorbitol and Sodiol Citrate citric acid pH buffering system provides chemical and physical stability for the liquid pharmaceutical compositions of the present invention and provide the liquid pharmaceutical compositions of the present invention with effective antimicrobial protection against microbial contamination for periods of at least 4 months and up to 36 months when stored at room temperature. (See Table 1). This particularly surprising and unexpected result is achieved without the use of standard preservatives such as sodium benzoate.

The present invention provides novel pharmaceutical formulations, which contain a combination of a non-sedating antihistamine and an expectorant or contain a combination of a non-sedating antihistamine, an expectorant and a nasal decongestant. The formulations of the invention are useful in the prevention and / or treatment of allergic and inflammatory conditions of the skin or passages of the airways with cough. The formulations are useful for a wide range of patient ages; The specific modalities provided here include a tablet form to be administered to humans 12 years of age and older, and a pediatric solution for humans aged 6-12 years. In addition, the invention provides methods for the treatment and / or prevention of allergic and inflammatory conditions with related cough in humans in need of such treatment and / or prevention, comprising the administration of an effective amount of a non-sedating antihistamine in combination with a expectorant. The phrase "allergic and inflammatory conditions of the skin or passages of the airways", as used herein, refers to those allergic and inflammatory conditions and symptoms found in the skin and in the upper and lower passages of the airways of the nose to the lungs. Allergic and inflammatory conditions and symptoms of the skin and in the upper and lower airways include seasonal and perennial allergic rhinitis, allergic rhinitis associated with cough; non-allergic rhinitis, asthma, including allergic and non-allergic asthma, sinusitis, colds, bronchopulmonary conditions of allergic origin associated with cough, in which the viscosity and adherence of the mucosa is increased, thus obstructing the permeability of the airways, acute, chronic, spasmodic and asthmatic bronchitis, bronchial asthma, bronchiectasis, sinusitis, otitis media; pneumonia; bronchopneumonia; atelectasis due to obstruction of the mucosa, and dermatitis, especially allergic and atopic dermatitis, and urticaria and symptomatic dermographism, as well as retinopathy, and small vein diseases, associated with diabetes mellitus. The term "a human being of 6-12 years", as used herein, refers to a male or female pediatric subject from 6 years of age to 12 years of age. The term "a human being 12 years and older", as used herein, refers to a male or female pediatric subject of more than 12 years or less than 18 years of age and adults 18 years of age and older. Although the preferred embodiments of the present invention comprise the treatment with loratadine and Ambroxol (See Examples 1 and 2), other antihistamines and expectorants can be applied in the same manner in the compositions and methods described herein. Below are non-inclusive lists of representative and expectorant antihistamines that can be used in the present invention.

I. Antihistamines Loratadine is a non-sedating antihistamine whose technical name is 11- (4-piperidinyl) -5H-benzo- [5,6] -cyclohepta- [1,2-b3-pyridine. The compound is described in U.S. Patent No. 4,282,233. Loratadine is a potent antihistamine and tricyclic drug with selective antagonistic activity of peripheral H receptors. The amount of loratadine that can be used in a unit (ie, single) dosage form of the compositions of the invention can vary from about 1.0 mg to about 15.0 mg, also from 2.5 mg to about 10.0 mg, preferably from about 5.0 mg to about 10.0 mg. Desloratadine is a long-acting non-sedating histamine antagonist with potent selective antagonistic activity of the peripheral H1 receptor. After oral administration, loratadine is metabolized rapidly in descarboethoxyloratadine or desloratadine, a pharmacologically active metabolite. U.S. Patent Nos. 4,659,716, 5,595,997 and 4,804,666 describe methods for performing desloratadine, pharmaceutical compositions containing it and methods for its use in the treatment of different disease states in mammals. The amount of desloratadine that can be used in a unit (ie, single) form of application of the dose of the present compositions can vary from about 0.75 mg to about 7.5 mg, and also from about 1.25 mg to about 5.0 mg, preferably from about 2.5 mg to about 5.0 mg. The descarboethoxyloratadine (DCL) is a non-sedating antihistamine, whose technical name is 8-chloro-6,11-dihydro-11- (4-piperidylidene) -5H-benzo [5,6j-cyclohepta [1,2] pyridine. This compound is described in Quercia, and his collaborators., Hosp. Formul., 28: 137-53 (1993), in U.S. Patent No. 4,659,716 and in WO 96/20708. DCL is an antagonist of the histamine H-1 receptor protein. The H-1 receptors are those that mediate the response antagonized by conventional antihistamines. H-1 receptors are present, for example, in the ileum, skin, and bronchial smooth muscle of man and other mammals. The amount of DCL that can be employed in a unit (ie, single) dosage form of the present compositions can range from about 2.5 to about 20 mg, also from about 5 to about 10 mg, preferably about 5 mg. mg or 7.5 mg. Fexofenadine (MDL 16,455A) is a non-sedating antihistamine, whose technical name is 4- [1-hydroxy-4- (4-hydroxy-diiphenylmethyl) -1-piperidinyl) butyr-a, a-dimethyl-benzenacetic acid. Preferably, the salt acceptable for pharmaceutical use is the hydrochloride, also known as fexofenadine hydrochloride. The amount of fexofenadine that can be used in a Unit dosage form of the present invention may vary from about 40 to about 200 mg, also from about 60 to about 180 milligrams, also about 120 milligrams.

II. Expectorants Ambroxol is a metabolite of bromhexine, chemically identified as trans-4 (2-amino-3,5-dibromobenzyl, amine) cyclohexane hydrochloride, which has been widely used for more than two decades as an expectorant or agent factor. pulmonary stimulant surfactant. The compound is described in U.S. Patent No. 3,536,712. The amount of ambroxol that can be used in a unit dosage form can vary from about 30.0 to about 60.0 mg, preferably about 60.0 mg. Guaiafennesin is an expectorant, whose technical name is 3- (2-methoxyphenoxy) -1,2-propanediol. The compound is described in U.S. Patent No. 4,390,732. The amount of guaiaphenesin that can be used in a unit dosage form can vary from about 300.0 to about 1,200.0 mg, preferably about 1, 200.0 mg Teffine hydrate is an expectorant whose technical name is 4-hydroxy-a, 4-trimethylcyclohexane-methanol. The amount of tephine hydrate that can be employed in a unit dosage form can vary from about 85.0 to about 680.0 milligrams. To prepare the pharmaceutical compositions from the compounds described in this invention, the inert diluents, acceptable for pharmaceutical use, the excipients and vehicles can be both solid and liquid. Solid form preparations include powders, tablets, dispersible granules, capsules (either solid-filled, semi-solid, or liquid-filled), sachets, and suppositories. The powders and tablets may comprise from about 5 to about 95 percent active ingredient. Suitable solid carriers are known in the art, for example, magnesium carbonate, magnesium stearate, talc, sugar, or lactose. The tablets, powders, sacks and capsules can be used as commercial dosage forms suitable for oral administration. Some examples of acceptable vehicles for pharmaceutical use and methods of manufacture for the different compositions can be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences, 18th. edition, (1990), Mack Publishing Co., Easton, Pennsylvania. Moreover, when desired, or needed, agglutinants, lubricants, disintegrating agents and coloring agents can be incoforated in the mixture as well. appropriate. Suitable binders include starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, propylene glycol and waxes. Among the lubricants that may be mentioned for use in these dosage forms are metal stearates, talc, starch powder, stearic acid, different grades of polyethylene glycol, and the like. The disintegrants include starch, methylcellulose, guar gum and the like. Sweetening and flavoring agents and preservatives may also be included where appropriate. Additionally, the compositions of the present invention can be formulated in sustained release form to deliver the rate of controlled release of one or more of the components or active ingredients to optimize the therapeutic effects. Suitable dosage forms for prolonged release include the tablets in layers containing layers of different rates of disintegration or controlled release polymer matrices impregnated with the active components and in the form of a tablet or capsules containing said impregnated or encapsulated porous polymer matrices. Liquid form preparations include solutions, suspensions and emulsions. Examples which may be mentioned are water or water-propylene glycol solutions for parenteral injection or the addition of sweeteners and softeners for oral solutions, suspensions and emulsions. Liquid form preparations may also include solutions for intranasal administration. Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be found in combination with a pharmaceutically acceptable carrier, such as an inert compressed gas, for example, nitrogen. Also included are solid form preparations which should be converted, just before use, into liquid form preparations for either oral or parenteral administration. Said liquid forms include solutions, suspensions and emulsions. The compounds of the invention can also be administered transdermally. The transdermal compositions can take the form of creams, lotions, aerosols and / or emulsions and can be included in a transdermal patch of the matrix or reservoir type which are conventional in the art for this purpose. Preferably, the compound is administered orally. Preferably, the pharmaceutical composition is a unitary form of dose application. In such form, the preparation is subdivided into unit doses with an appropriate size containing the appropriate quantities of the active component, for example, an effective amount to achieve the desired purpose.

The amount of active compound in a unit dose of preparation can be varied or adjusted from about 0.01 mg to about 1,000 mg, preferably from about 0.01 mg to about 750 mg, more preferably from about 0.01 mg to about 750 mg and more preferably from about 0.01 mg to about 250 mg according to the particular application. The actual dose used can be varied depending on the requirements of the patient and the severity of the condition being treated. The determination of the appropriate dose regimen for a particular situation is within the skill in the art. For convenience, the total daily dose may be divided and administered in portions during the day as required. The amount and frequency of administration of the compounds of the invention will be regulated according to the criteria of the physician attending the patient after considering factors such as the age, condition and size of the patient, as well as the severity of the symptoms a try. A recommended daily dose regimen for oral administration may vary from about 5.0 to 10.0 mg / day of loratadine and 30 to 60.0 mg / day of ambroxol, in two to four divided doses. Form of application of the dose - non-sedating and expectorant antihistamine formulated in a release system, ie, compressed, capsule, oral gel, powder for constitution or suspension in association with inactive ingredients. Capsule - refers to a container or special enclosure made of methylcellulose, polyvinyl alcohols, or denatured gelatins or starch to hold or contain compositions comprising non-sedating antihistamine and an expectorant. Hard capsules are usually made with mixtures of pig skin gelatins and high gel strength bone.

The capsule itself may contain small amounts of dyes, opacifiers, plasticizers and preservatives. "Compressed" - refers to a solid, compressed or molded form, of application of the dose containing the active ingredients with appropriate diluents. The tablet can be prepared by compression of mixtures or granulations obtained by wet granulation, dry granulation or by compaction. Oral gels - refers to a non-sedating antihistamine and an expectorant dispersed or solubilized in a hydrophilic semisolid matrix. Powders for constitution - refers to mixtures of powders that contain the appropriate active ingredients and diluents that can be suspended in water or juice. Diluent - refers to substances that usually make up the main portion of the composition or dosage form. Suitable diluents include sugars such as lactose, sucrose, mannitol and sorbitol; starches derived from wheat, corn, rice and potatoes; and the celluloses as microcrystalline cellulose. The amount of diluent in the composition may vary from about 10 to about 900/9 by weight of the total composition, preferably from about 25 to about 75%, more preferably from about 30 to about 60% by weight, even with greater preference of about 12 to about 60%. Disintegrators - refers to materials added to the composition to help break up (disintegrate) and release medications. Suitable disintegrants include starches; Modified "cold water soluble" starches such as sodium carboxymethyl starch, natural and synthetic gums such as acacia beans, karaya, guar, tragacanth and agar, cellulose derivatives, such as methylcellulose, and sodium carboxymethylcellulose, the microcrystalline celluloses and interlaced microcrystalline celluloses such as croscarmellose sodium, alginates such as alginic acid and sodium alginate, clays, such as bentonites, and effervescent mixtures, such as povidone crosslinkers.The amount of disintegrant in the composition can vary from about 2 to about 15% by weight of the Composition, more preferably from about 4 to about 10% by weight Binders - refers to substances that agglutinate or "stick" the powders and convert them into cohesives through the formation of granules, thus serving as the "adhesive" in the formulation. The binders add cohesive strength already available in the diluent or the volumetric agent. Suitable binders include sugars such as sucrose; starches derived from wheat, corn, rice and potatoes; natural gums such as acacia, gelatin and tragacanth; seaweed derivatives such as alginic acid, sodium alginate and calcium alginate ammonium; cellulose materials such as methylcellulose and sodium carboxymethylcellulose and hydroxypropylmethylcellulose; polyvinyl pyrrolidone; and inorganic, such as magnesium aluminum silicate. The amount of binder in the composition may vary from about 2 to about 20% by weight of the composition, more preferably from about 3 to about 10% by weight, even more preferably from about 3 to about 6% by weight. Lubricant - refers to a substance added in the dosage form to allow the tablet, granules, etc. After being compressed, they are released from the mold or die by friction or reduced wear. Suitable lubricants include metal stearates such as magnesium stearate, calcium stearate or potassium stearate; stearic acid; waxes of high melting point; and water-soluble lubricants, such as sodium chloride, sodium benzoate, sodium acetate, sodium oieate, polyethylene glycols and d'l-leucine. The lubricants are added, in general, in the last step before compression, since they must be present on the surfaces of the granules and between them and the parts of the press of the compressed. The amount of lubricant in the composition can vary from about 0.2 to about 5% by weight of the composition, preferably from about 0.5 to about 2%, more preferably from about 0.3 to about 1.5% by weight. Slides - materials that prevent the formation of cake and improve the flow characteristics of the granulations, so that the flow is smooth and uniform. Suitable glidants include silicon dioxide and talcum. The amount of glidant in the composition may vary from about 0.1% to about 5% by weight of the total composition, preferably from about 0.5 to about 2% by weight. Coloring agents - excipients that supply coloration to the composition or dosage form. Such excipients may include food grade colorants or food grade colorants adsorbed on a suitable adsorbent such as clay or aluminum oxide. The amount of coloring agent may vary from about 0.1 to about 5% by weight of the composition, preferably from about 0.1 to about 1%. Bioavailability - refers to the rate and extent to which the drug active ingredient or therapeutic functional group is absorbed into the systemic circulation from a dosage form administered when compared to a standard or control.

The conventional methods for preparing tablets are known. These methods include dry methods, such as compression direct and compression of the granulation produced by compaction, or the wet methods, or other special procedures.

The broad scope of this invention is best understood with reference to the following examples, which do not intend to limit the invention to specific modalities.

The present invention is further described by means of of the following examples that are not intended to limit the scope of the present invention as defined by the claims that the accompany EXAMPLE 1 Ingredient mq / ml OHOOOL Loratadine 0.50 500 Pseudoephedride sulphate 6.00 6,000 Glycerin 200.00 200,000 Propylene glycol 350.00 350,000 Sorbitol 70% solution 225.00 225,000 Saccharin sodium 0.40 400 Peanut flavoring No. 609 J 2.50 2,500 Citric acid, anhydride 0.64 640 Sodium citrate 0.02 20 Purified water is . s. To form 1.00 ml 1, 000L A solution was formulated containing the following ingredients: A batch of 1 000 L of the solution of Example 1 is prepared using the following procedure: 1. In a tank to form stainless steel compounds, of the appropriate size, equipped with a stainless steel stirrer, the polyethylene glycol is charged, Stir slowly and heat to 40 ° C ± -5 ° C. 2. Loratadine is charged to the propylene glycol heated in step 1. Stirring is continued until it is completely dissolved. 3. The mixing is maintained and the glycerin USP and the sorbitol solution were loaded to the batch from step 2. Mixing was continued until the batch remained homogeneous. 4. In a stainless steel vessel of adequate size, equipped with a stainless steel stirrer, 40 liters of purified water are charged and agitation was initiated. The following ingredients are charged to the purified water; sodium saccharin, sodium citrate, citric acid, and pseudoephedrine sulfate, making sure that each ingredient was dissolved before starting the addition of the next. 5. Add the active solution from step 4 to the batch obtained in step 3; using purified water to rinse the container of the active solution several times (2 to 3 liters, three times), and adding two rinses to the batch. Mix until the batch was homogeneous. 6. Agitation is maintained and a peach flavor is loaded onto the batch obtained in step 5, mixing until homogeneous. 7. The pH is checked and adjusted to a value of 35 + 0.1 using citric acid as a 10% solution in purified water. The volume of the added solution and the resulting pH are recorded. 8. Bring the batch to the volume (1, 000 liters) with purified water and mix until homogeneous. 9. The batch is filtered through an Ertel filter press (or its equivalent) equipped with a suitable asbestos-free filter, circulating the batch back in the tank until the outgoing filtrate was clear and bright. The batch is then filtered in a suitable stainless steel container tank. 10. It is filled in approved containers. Typically suitable containers for the liquid compositions of the present invention include amber type lll glass containers and a high density polyethylene ("HDPE") container. It is stored in conditions between 2 ° and 30 ° C.

EXAMPLE 2 The procedure of Example 1 is used to prepare the following solution.

Ingredient mg / ml Loratadine 0.50 Pseudoephedride sulphate 6.00 Glycerin 200.00 Propylene glycol 350.00 Sorbitol solution 70% 225.00 Saccharin sodium 0.40 Peanut flavoring No. 609 2.50 Citric acid, anhydride 0.64 Sodium citrate 0.02 Purified water is. To form 1.00 m The formulation of the solution can also be stored in a 30 mL lll amber glass bottle with dropper caps It is also possible to use opaque white bottles of 30 mL HPDE. The formulation of the solution of Example 1 was stored in amber glass bottles type III 30 mL with a flat lid with a vinyl on the lining of the lid room temperature, 35 ° and 45 ° C. Samples were removed and tested to assess degradation by HPLC, with the use of loratadine and pseudoephedrine standards. PH, Alpha and APE tests were also carried out. The results are summarized in Table 1.

Similar results were expected for the formulation of the solution of Example 2.

It is indicated that the formulations of the solution of Examples 1 and 2 are useful for the treatment of pediatric patients from 2 to 8 years of age for relief of symptoms associated with allergic rhinitis and the common cold, including nasal congestion, sneezing, runny nose, pruritus and tearing. In addition, the formulations of the solution of the present invention are useful when both the antihistamine properties of loratadine and the decongestant properties of pseudoephedrine sulfate in any patient are desired., including pediatric patients 2-8 years of age and older. Then, the pharmaceutical compositions. liquid, stable of the present invention are useful for the relief of symptoms associated with congestion of the upper passage of the airways associated with disorders such as seasonal and perennial allergic rhinitis and for the relief of symptoms associated with upper respiratory infections such as the common cold, which includes nasal congestion. The attending physician will determine the precise dose and dosage regimen according to the age and medical condition of the patient, as well as the severity of the symptoms associated with congestion of the upper airway passage and the severity of the Symptoms associated with upper respiratory infections, such as the common cold, which includes nasal congestion. The liquid pharmaceutical compositions of the present invention containing 0.50 mg / ml loratadine and 6.0 mg / ml sulfate pseudoephedrine can be administered to a human pediatric patient from 2 to 8 years of age according to the following regimen: The liquid pharmaceutical compositions of the present invention containing 1.00 mg / ml of loratadine and 6.0 mg / ml of pseudoephedrine sulfate can be administered to a human pediatric patient from 2 to 8 years of age according to the following regimen: EXAMPLES 3A-D New Pharmaceutical Compositions The present invention provides a novel combination of a slow release non-sedating antihistamine such as loratadine, and an expectorant and a mucolytic agent such as ambroxol, in a new pharmaceutical preparation. The combination is indicated mainly in the treatment of those patients who present broncho-pulmonary conditions of allergic origin associated with cough, in which the viscosity and mucous adhesion are increased, obstructing the permeability of the airways. The main indications include, but are not limited to, allergic rhinitis, associated with cough; acute, chronic, spasmodic and asthmatic bronchitis; bronchial asthma; bronchiectasis; sinusitis; otitis media; pneumonia; bronchopneumonia; atelectasis due to mucosal obstruction; trecheotomy as a pre and post prophylactic agent.

EXAMPLE 3A Ingredients Name Concentration Basis% V 'ariació (mg / tablet) Loratadine 5.00 Active Ambroxol Hydrochloride 30.00 Active Pseudoephedrine Sulphate 60.00 Active Anhydrous Lactose 80.75 Filling ± 20 Corn Starch 12.00 Disintegrant ± 20 Microcrystalline Cellulose 16.75 Disintegrant ± 10 Silicon Dioxide colloidal 0.75 Sliding ± 10 Magnesium stearate 0.75 Lubricant ± 10 Tablet weight 210.00mg Manufacturing Procedure: 1. It is loaded in a stainless steel two-body mixer appropriate size the Micronized Loratadine, the colloidal silicon dioxide and about half the amount of anhydrous lactose. Mix for 10 minutes. 2. The contents of the mixer obtained in the Step 1 and pass the mixture through a mechanical sieve or Oscillator equipped with a 40 mesh and the sample is returned to the two-batch mixer. 3. The remaining amount of anhydrous Lactose is passed through the same mechanical sieve or oscillator from step 2 and the mixture is returned to the mixer from step 2. 4. The hydrochloride is charged in the mixer from step 2 ambroxol, pseudoephedrine sulfate, corn starch, cellulose microcrystalline Mix for 20 minutes. 5. It is loaded into the mixer from step 2, the stearate magnesium. Mix for 3 minutes. 6. The contents of the mixer from step 5 are downloaded, containers suitable for storage, covered with bags of polyethylene; the bags are tied separately, and the weight is recorded. 7. With the use of an appropriate press for tablets, compress the mixture from step 6 and obtain tablets.

EXAMPLE 3B Ingredients Name Concentration Basis% Variad (mg / tablet) Loratadine 1.00 Active Ambroxol Hydrochloride 6.00 Active Pseudoephedrine Sulfate 12.00 Active Citric acid 0.40 Regulating Sun ± 10 Glycerin 150.00 Solvent ± 20 Propylene glycol 200.00 Solvent ± 20 Sodium saccharin 0.40 Sweetener ± 10 Sorbitol solution 70% 450.00 Solvent ± 20 Flavor 2.50 Flavor ± 10 Purified water is. Solvent ± 20 To form 1.00 ml 1. Peach Flavor No. 609.

Manufacturing process: 1. In a tank to form stainless steel compounds, of adequate size, polyethylene glycol is loaded; The following is added and dissolved: sodium saccharin, micronized loratadine. You must be sure that each ingredient is dissolved before adding the next one. 2. In a tank of stainless steel compound, fitted with a jacket, of a suitable size, equipped with a stainless steel stirrer, a portion of the Purified Water is charged and heated to 60 ° C-65 ° C. 3. With continuous agitation, citric acid is added and dissolved. Mix thoroughly until a clear solution is obtained. The solution is loaded into the batch and mixed until it is homogeneous. The tank is rinsed with two portions of purified water. 4. The batch is cooled and the temperature is maintained at 40 ° C-45 ° C. 5. With continuous stirring, the Ambroxol Hydrochloride, Pseudoephedrine Sulfate, is added and dissolved. Mix thoroughly until a clear solution is obtained. 6. Glycerin is loaded into the batch and mixed until homogeneous. 7. The Sorbitol Solution is loaded into the batch and mixed until homogeneous. The batch is cooled to room temperature (20 ° C-25 ° C). 8. The artificial flavor is loaded into the batch and mixed until it is homogeneous. 9 Control and adjust the pH up to 2.9 ± 0.2 if necessary with 1% Citric acid solution or 0.1 N Sodium Hydroxide solution 10. The batch is brought to volume with purified water and mixed until it is homogeneous. 11. The batch is filtered through an Ertel filter press (or its equivalent) equipped with a suitable asbestos-free filter, making circulate the batch back in the tank until the outgoing filtered product It was clear and bright. The batch is then filtered in a container tank Suitable stainless steel.

EXAMPLE 3C Ingredients Name Concentration Basis% V 'ariació (mg / tablet) Loratadine 3.33 Active Ambroxol Hydrochloride 30.00 Active Pseudoephedrine Sulphate 60.00 Active Lactose anhydride 76.42 Filler ± 20 Corn starch 12.00 Disintegrant ± 20 Microcrystalline cellulose 16.75 Disintegrant ± 10 Silicon dioxide colloidal 0.75 Slider ± 10 Magnesium stearate 0.75 Lubricant ± 10 Tablet weight 200.00mg Manufacturing process: 1. Micronized Loratadine, colloidal silicon dioxide and about half the amount of anhydrous lactose are charged in a stainless-steel blender of suitable size. Mix for 10 minutes. 2. The contents of the mixer obtained in step 1 are discharged and the mixture is passed through a mechanical sieve or Oscillator equipped with a 40 mesh and the sample is returned to the two-batch mixer. 3. The remaining amount of anhydrous lactose is passed through the same mechanical sieve or oscillator from step 2 and the mixture is returned to the mixer from step 2. 4. The mixer from step 2 is charged with ambroxol hydrochloride, sulfate pseudoephedrine, corn starch, microcrystalline cellulose. Mix for 20 minutes. 5. Magnesium stearate is charged in the mixer of step 2. Mix for 3 minutes. 6. The contents of the mixer from step 51 are discharged into suitable containers for storage, covered with polyethylene bags; the bags are tied separately, and the weight is recorded. 7. With the use of an appropriate press for tablets, the mixture from step 6 is compressed and tablets are obtained. 3D EXAMPLE Ingredients Name Concentration Basis% \ ariaci (mg / tablet) Loratadine 1.00 Active Ambroxol Hydrochloride 6.00 Active Pseudoephedrine Sulfate 8.00 Active Citric acid 0.40 Regulating Sun ± 10 Glycerin 150.00 Solvent ± 20 Propylene glycol 200.00 Solvent ± 20 Sodium saccharin 0.40 Sweetener ± 10 Sorbitol solution 70% 448.00 Solvent ± 20 Flavor 2.50 Flavor ± 10 Purified water is. Solvent ± 20 To form 1.00 ml 1. Peach Flavor No. 609.

Manufacturing procedure: 1. In a tank to form stainless steel compounds, of suitable size, polyethylene glycol is charged; it is added and dissolved next: sodium saccharin, micronized ioratadine. You must be sure of that each ingredient is dissolved before adding the next one. 2. In a tank of formation of steel compounds stainless steel, provided with a shirt, of a suitable size, equipped with a stainless steel agitator, a portion of the Purified Water is loaded and It heats up to 60 ° C-5 ° C. 5. With continuous agitation, the Ambroxol Hydrochloride, Pseudoephedrine Sulfate, is added and dissolved. Mix thoroughly until a clear solution is obtained. 6. Load the Giicerina into the batch and mix until homogeneous. 7. The Sorbitol Solution is loaded into the batch and mixed until homogeneous. The batch is cooled to room temperature (20 ° C-25 ° C). 8. The artificial flavor is loaded into the batch and mixed until it is homogeneous. 9. Control and adjust the pH to 2.9 + 0.2 if necessary with 1% Citric Acid Solution or 0.1 N Sodium Hydroxide Solution. 10. Bring the batch to volume with Purified Water and mix until homogeneous. . 11. The batch is filtered through an Ertel filter press (or its equivalent) equipped with a suitable asbestos-free filter, circulating the batch back in the tank until the outgoing filtrate was clear and bright. The batch is then filtered in a suitable, stainless steel container tank.

Dosage and Administration For the Tablets of Examples 3A and 3C, adults and children 12 years of age and older can take two tablets per day of the preparations according to Example 3A and three tablets per day of the preparations according to Example 3C The solutions of Examples 3B and 3D can be administered as follows: (1) Adults and children 12 years and older can take 5 ml (1 teaspoon) of the solution of Example 3B twice a day (IDB) ) or 5 ml (1 tea spoon) of the solution of Example 3D three times per day (TID); (2) Children from 6 years to less than 12 years old can take 2.5 ml (1/4 teaspoon of tea) from the solution of Example 3B twice per day 2.5 ml (1/4 teaspoon) of the solution of Example 3D three times per day; and (3) Children from 2 years to less than 6 years old can take 1.25 ml (1/2 teaspoon) of the solution of Example 3B twice a day or 1.25 ml (1/2 teaspoon) of tea. Example 3D solution three times per day. Of course, the doctor to fall can adjust the precise dose and frequency of administration of the pharmaceutical compositions of the present invention according to the age of the patient, the weight, the severity of the disease and other health problems.

Clinical Studies The safety and efficacy of each component separately from the combination of loratadinal ambroxol, and the combination of loratadinal ambroxoil pseudoephedrine are well established. Acute toxicity studies performed with the loratadine components (in extensive clinical and preclinical programs), pseudoephedrine and ambroxol have confirmed the low potential for systemic toxicity, which was expected for these combinations. Those skilled in the art can make other modifications to the formulations of the present invention. Typical additional appropriate drugs include analgesics such as aspirin, acetaminophen, ibuprofen, naproxen or ketoprofen for pain relief and, except in the case of acetaminophen, relief of inflammation Antitussives, such as codeine, hydrocodone or dextromethorphan, for the relief of cough, and expectorants such as guaifenesin, to increase the productivity of cough, can also be included in the syrup formulations to form combined products. Any of these additional drugs, including their salts, and other drugs of the same kinds can be added to the formulations of the solution without moving away of the scope of the present invention.

Claims (27)

NOVELTY OF THE INVENTION CLAIMS

1. - A stable pharmaceutical composition characterized in that it comprises an effective amount of loratadine or a pharmaceutically acceptable salt thereof and an elective amount of a nasal decongestant or a pharmaceutically acceptable salt thereof and, optionally, an effective amount of a expectorant or one of its acceptable salts for pharmaceutical use and, at least, a vehicle acceptable for pharmaceutical use.

2. A stable pharmaceutical composition characterized in that it comprises an effective amount of loratadine or a pharmaceutically acceptable salt thereof and an effective amount of pseudoephedrine or a pharmaceutically acceptable salt thereof and at least one acceptable carrier for use pharmacist.

3. A stable pharmaceutical composition characterized in that it comprises an effective amount of loratadine or one of its acceptable salts for pharmaceutical use and an effective amount of a nasal decongestant or one of its pharmaceutically acceptable salts and an effective amount of an expectorant or a of its acceptable salts for pharmaceutical use and, at least, a vehicle acceptable for pharmaceutical use.

4. - The pharmaceutical composition according to any of the preceding claims, further characterized in that the nasal decongestant is pseudoephedrine or one of its acceptable salts for pharmaceutical use.

5. The pharmaceutical composition according to claim 1 or 3, further characterized in that the stable pharmaceutical composition is a liquid dosage form and contains at least one liquid vehicle acceptable for pharmaceutical use.

6. The pharmaceutical composition according to claim 1 or 3, further characterized in that the stable pharmaceutical composition is a solid dosage form.

7. The pharmaceutical composition according to claim 2 or 5, further characterized in that it contains an antimicrobial effective amount of a sweetener, propylene glycol and glycerin.

8. The pharmaceutical composition according to claims 1, 2 or 3, further characterized in that it contains about 0.4 to about 0.7 mg / ml of loratadine.

9. A liquid pharmaceutical composition, stable to microbial contamination, characterized in that it comprises: an effective amount of pseudoephedrine or phenylpropanolamine or one of its pharmaceutically acceptable salts, and a combination of (1) a sweetener, (2) at least one liquid vehicle acceptable for pharmaceutical use, and (3) an amount of pH regulating system to maintain sufficient pH in the range of about 3.0 to about 5.0.

10. A liquid pharmaceutical composition, stable to microbial contamination, characterized in that it comprises an effective amount of pseudoephedrine or phenylpropanolamine or one of its acceptable ones for pharmaceutical use, and an effective amount of an expectorant or one of its salts acceptable for use. pharmaceutical, and, at least, a vehicle acceptable for pharmaceutical use.

11. The pharmaceutical composition according to claim 10, further characterized in that the stable pharmaceutical composition is a liquid dosage form and contains a combination of (1) a sweetener, (2) at least one liquid carrier acceptable for pharmaceutical use. , and (3) an amount of pH regulating system to maintain sufficient pH in the range of about 3.0 to about 5.0.

12. The pharmaceutical composition according to claim 10, further characterized in that the stable pharmaceutical composition is a solid dosage form.

13. The pharmaceutical composition according to claim 9 or 10, further characterized in that the sweetener is a combination of sodium saccharide and sorbitol.

14. A liquid, stable pharmaceutical composition, characterized in that it comprises: ingredients: loratadine 0.50 mg / mg; sulfate of pseudoephedride 6.00 mg / mg; Giicerin 200.00 mg / mg; propylene glycol 350.00 mg / mg; 70% sorbitol solution 225.00 mg / mg; sodium saccharin 0.40 mg / mg; peach flavor No. 609 2.50 mg / mg; citric acid, anhydride 0.64 mg / mg; sodium citrate 0.02 mg / mg; purified water enough quantity to form 1.00 ml.

15. A liquid, stable pharmaceutical composition comprising: ingredients: loratadine 0.50 mg / mg; pseudoephedride sulfate 6.00 mg / mg; Glycerin 200.00 mg / mg; propylene glycol 350.00 mg / mg; 70% sorbitol solution 225.00 mg / mg; sodium saccharin 0.40 mg / mg; peach flavor No. 609 2.50 mg / mg; citric acid, anhydride 0.64 mg / mg; sodium citrate 0.02 mg / mg; purified water sufficient quantity to form 1.00

16. The liquid pharmaceutical composition according to any of the preceding claims, further characterized by being stable to microbial contamination for periods of at least 4 months, preferably up to 36 months of storage at room temperature.

17. The liquid pharmaceutical composition according to any of the preceding claims, characterized in that it is stable to the chemical and physical degradation of the active ingredients for periods of at least 4 months, preferably up to 36 months of storage. at room temperature.

18. - The liquid pharmaceutical composition according to any of the preceding claims, further characterized in that it is stable to microbial contamination and chemical and physical degradation of the active ingredients for periods of at least 4 months, preferably up to 36 months. months of storage at room temperature.

19. The liquid pharmaceutical composition according to any of the preceding claims, further characterized in that it substantially does not contain sugar such as glucose or sucrose and ethanol and is suitable for pediatric use.

20. The use of ioratadine and a nasal decongestant for the preparation of a liquid pharmaceutical composition for the treatment of symptoms associated with allergic reactions comprising an effective amount of a non-sedating antihistamine in combination with an effective amount of a nasal decongestant.

21. The use of loratadine and a nasal decongestant for the preparation of a liquid pharmaceutical composition for the treatment of symptoms associated with allergic rhinitis and the common cold comprising an effective amount of a non-sedating antihistamine in combination with an effective amount of a nasal decongestant.

22. The use of loratadine and a nasal decongestant for the preparation of a liquid pharmaceutical composition for the treatment of symptoms associated with allergic rhinitis and the common cold, including nasal congestion, sneezing, rhinorrhea, pruritus, and lacrimation, comprising an effective amount of a non-sedating antihistamine in combination with an effective amount of a nasal decongestant.

23. The use of a non-sedating antihistamine in combination with an expectorant and a nasal decongestant for the preparation of a medicament for the treatment of allergic and inflammatory respiratory conditions with cough, nasal congestion and the presence of mucus in the respiratory tract comprising an effective amount of a non-sedating antihistamine in combination with an effective amount of an expectorant, and an effective amount of a nasal decongestant.

24. The use as claimed in claim 20-24, wherein the decongestant is pseudoephedrine or one of its acceptable salts for pharmaceutical use.

25. The use as claimed in claim 20-24, wherein the liquid pharmaceutical composition is stable to contamination by microbes for periods of at least 4 months, preferably up to 36 months of storage at room temperature.

26. The use as claimed in claim 20-24 wherein the liquid pharmaceutical composition is stable to the chemical and physical degradation of the additive ingredients for periods of at least 4 months, preferably up to 36 months of storage at room temperature.

27. - The use as claimed in claim 20-24 wherein the liquid pharmaceutical composition is stable to microbial contamination and chemical and physical degradation of the active ingredients for periods of at least 4 months, preferably up to 36 months. months of storage at room temperature.