MXPA97005724A

MXPA97005724A - Liquids that hide the sa

Info

Publication number: MXPA97005724A
Application number: MXPA/A/1997/005724A
Authority: MX
Inventors: Dass Popli Shankar; Ong Go Zenaida
Original assignee: American Home Products Corporation
Priority date: 1995-01-30
Filing date: 1997-07-29
Publication date: 1998-07-03

Abstract

A liquid excipient base is provided which hides the taste for the administration of relatively large quantities of tasting drugs, the aforementioned excipient base has higher viscosities than normal due to a combination of polyethylene glycol and the cellulosic material.

Description

LIQUIDS THAT HIDE THE TASTE BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to a liquid carrier base which conceals the acceptable pharmaceutical taste for the administration of a relatively large amount of unpleasant tasting medicines. More specifically, the effect of concealing the taste is produced by increasing the viscosity of the liquid carrier base by adding to the liquid excipient base an amount that increases the viscosity of a combination of polyethylene glycol and sodium carboxymethyl cellulose not badly. solid The invention is then directed to medical compositions that consist of the claimed liquid excipient base and the aforementioned unpleasant tasting medicines.

Even later, the invention is directed to a method for unpleasant tasting meditations that hide the flavor by its incorporation into the liquid excipient bases claimed.

BACKGROUND OF THE INVENTION REF: 25316 Pharmaceutically acceptable liquid excipient bases for the administration of degustable tasting medicines are well known in the art. A typical system - described in United States Letters No. 5,260,073 - by Roger J. Phipps in column 7 as it includes a medicine, a solvent, a co-solvent, a buffer, a surfactant, - a preservative, a sweetening agent, a flavoring agent, - a dye or pigment, a viscosity modifier and water. The pineapple provides several examples of each ingredient in the Sikhs theme.

Although the liquid excipient bases and their many ingredients are well known, the unpleasant tasting drugs alone or in combination still present require an expert in the art to provide better products that hide the taste and, in a certain instance, to provide products. They hide the taste for greater amounts of desification of unpleasant tasting medicines in smaller amounts of vehicle.

BRIEF DESCRIPTION OF THE INVENTION The present invention provides a liquid carrier base which conceals the taste to pharmaceutically available for the administration of relatively large amounts of pharmaceutically active compounds of unpleasant tasting in which the liquid excipient base consists of polyethylene glycol having a molecular weight of at least 1000 and a cellulosic material, the viscosity of the excipient base axis being between about 150 - and almost 1000 centipoise at 50 RPM.

The invention further provides pharmaceutically acceptable taste-hiding liquid excipient bases for the administration of relatively large amounts of pharmaceutically active compounds of unpleasant tasting.

Surprisingly, it has been found that the high viscosity liquid carrier base provides benefits in the concealment of taste to the point that even extra strength formulations containing increasing concentrations of pharmaceutically active compounds of adverse tasting. For example, guaifenaseña, normally administered in doses of no more than 100 milligrams in 5 milliliters of liquid, can be administered in doses of 200 milligrams with the same volume of liquid outside of which the patient experiences an excessively adverse taste.

DETAILED DESCRIPTION OF THE INVENTION The pharmaceutically acceptable taste-hiding bases in this invention are those which contain therein, per 100 milliliters of liquid base almost 5 to almost 20 grams, preferably almost 10 to almost 15 grams of polyethylene glycol - having an average molecular weight of almost 950 to almost 2200, -preferably almost 1400 to almost 1600, and a cellulose material, the weight ratio of polyethylene glycol. against the ce lulosic material it is between almost 100: 1 and almost 20: 1, such that the viscosity of the spindle is "between almost 150 and almost 1000 centipoise at 50-RPM." These bases typically have a spindle viscosity of almost-150 to almost 1200 centipoise when measured at 10 RPM.The higher viscosities of these bases are preferred for certain applications, then such liquids are easier to pour into glass bottles and do not tend to spill from a spoon -during their administration, especially for children.

The pH of the liquid base is from about 2.5 to almost 5. At a lower pH, the cellulosic material may tend to crystallize, and at a higher pH, the worst flavors and preservatives may be used.

The polyethylene glycol useful in the practice of the present invention are those having an average molecular weight of almost 950 to almost 2200. Preferably, the polyethylene glycol has an average molecular weight of almost 1400 to almost 1600. More preferably, the polyethylene glycol used in the The practice of the present invention has an average molecular weight of almost 1450. The use of mixtures of such polyethylene glycols is also within the practice of the present invention. As indicated above, the polyethylene glycol compound is used in an amount of 10 to almost 15 grams per 100 milliliters of the liquid excipient base. The polyethylene glycol in the specific examples was polyethylene glycol 1450 N.F. This polyethylene glycol, which has an average molecular weight of 1450 can be obtained from a number of supplies. For example, it is sold by Union Carbide Chemicals and Plastics Company, Inc. of Dubury, CT as CARBOWAX 1450R and by DOW Polyglycol E 1450.

The cellulosic materials useful in the practice of the present invention are food grade materials and include methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose and mixtures thereof. Also useful are salts of such materials, such as the sodium salt of carboxymethyl cellulose, typically produced by the neutralization of sodium hydroxide from a derivative of the cellulose carboxylic acid.

The use of such sodium salt of carboxymethyl cellulose is preferred. As stated above, such materials are used-in amounts such that (a) the proportion of polyethylene glycol: cellulosic material is between nearly 100: 1 and almost 20: 1 and (b) the spindle viscosity of the liquid excipient bases are between almost 150 and almost 1000 centipoise at 50 RPM. In a preferred embodiment of the present invention wherein the cellulosic material is the sodium salt of carboxymethyl cellulose, such material is present in amounts between about 0.05 and about 0.6 grams, preferably between about 0.1 and about 0.5 grams, per 100. milliliters of the liquid excipient bases.

The cellulose material in the specific examples was used cellulose gum HERCULES * ^ 7MF which is the sodium salt of Carboxymethyl cellulose with a minimum purity of 99.5%, food grade, with a Grade Type 7 Substitution and a range of average viscosity of 400-800 cps with 2% by weight of water solution. The pharmaceutically active compounds and other excipients that polyethylene glycol and sodium carboxymethyl cellulose were U.S.P.

Pharmaceutically active compounds useful in the practice of the present invention include antihistaminic, decongestant, antitussive, expectorant, non-steroidal anti-inflammatory drugs (NSAIDs and other analgesic drugs - such as acetaminophen and phenacetin.) These materials are contained within the liquid excipient base claimed in quantities governed by the solubility of the material in such excipient base and such that the conventional doses thereof will be inflexible with the applicable FDA regulations For example, the materials highly soluble in the liquid carrier base are not The point that a typical dose (such as a spoonful) contains, more than such material as allowed by such regulations, can be incorporated.

Among the antihistamines useful in the practice of the present invention (together with their preferred salt form) are chlorpheniramine (maleate), brompheniramine (maleate), dexchlorpheniramine (maleate), dexbrompheniramine (maleate), triprolidine (HC1), diphenhydramine ( HC1), cyproheptatin (HC1), bromohydrazine (HC1), fenindamine (tartrate), pyrilamine (maleate, tannante) and azatadine (maleate).

Antitussives useful in the practice of the present invention - (together with its preferred salt form) are pseudoephedrine (HC1), phenylpropane sheet (HC1) and phenylephrine (bitartrate, tannate, HBr, HC1). Phenylpropanolamine (HC1) has been found unsuitable for use in the present invention if the high fructose corn syrup sweetener is present. Therefore, if phenylpropanolamine HC1 is used in conjuntion with a sweetener, a sweetener such as sorbitol is employed.

Expectorants useful in the practice of the present invention - (together with its preferred salt form) are terpine hydrate, guaifenesin (glyceryl guaiacolate), potassium (iodide, citrate) and potassium guaicolsulfonate.

Non-steroidal anti-inflammatory drugs (NSAIDs) for use in the practice of the present invention can be selected in-form, any of the following categories: (1) propionic acid derivatives; (2) acetic acid derivatives; (3) derivatives of fenamic acid; (4) biphenylcarboxylic acid derivatives; and (5) oxicams.

The propionic acid derivatives for use herein, ibuprofen, naproxen, ketoprofen, flurbiprofen, fenoprofen, suprofen, fenbufen, and fluprofen may be mentioned as preferred compounds.

The acetic acid derivatives to be used herein, sodium tolmetin, zomepirac, sulindac and indomethacin are included.

The derivatives of the fenamic acid to be used herein, mefenamic acid and sodium meclofenamate are included.

Diflunisal and flufenisal are derivatives of biphenylcarboxylic acid.

Oxicams include piroxicam, sudoxicam and isoxicam.

Of course, it will be appreciated by those skilled in the art that any of the aforementioned compounds can be used in the form of their pharmaceutically acceptable salt forms, e.g. -C00 Na, --C00, and the like.

The aforementioned NSAIDs, ibuprofen and naproxen are most preferred.

Other analgesic compounds useful in the practice of the present invention include acetaminophen and phenacetin.

The pharmaceutically active compounds described above, which are particularly preferred for inclusion in the claimed excipient-liquid base.

Iña guarenes can be presented in an amount of up to 300 milli grams per 5 milliliters of the excipient base. Preferably, guaifenesin is present in amounts of almost 10 to almost 300 milligrams per 5 milliliters of the excipient base. More preferably, quaifenesin is present in amounts of almost 100 to almost 200 milligrams per 5 milliliters of the base-excipient.

Dextromethorphan can occur in amounts between almost 5 and -almost 20 milligrams per 5 milliliters of the excipient base. More preferably, dextromethorphan is present in amounts of almost 10 to almost 15 milli grams per 5 milliliters of the excipient base.

Brompheniramine may be present in an amount between about 0.5 and about 4.0 milligrams per 5 milliliters of the excipient base. More preferably, brompheniramine is present in amounts of almost 2.0 milligrams - per 5 milliliters of the excipient base.

The pseudoephedrine can be present in an amount between 10 and almost 60 milligrams per 5 milliliters of the excipient base. More preferably, pseudoephedrine is present in amounts of almost 15 to almost 30 milligrams per 5 milliliters of the excipient base.

Acetaminophen can be present in amounts up to almost 200 milligrams per 5 milliliters of the excipient base. Preferably, acetaminophen is present in amounts of almost 50 to almost 200 milligrams per 5 milliliters of the excipient base. More preferably, acetaminophen is available in amounts of about 150 to about 175 milligrams per 5 milliliters of the excipient base.

Ibuprofen can be present in quantities of up to almost 150 milli grams per 5 milliliters of the excipient base. Preferably this is preserved in amounts between almost 50 and almost 150 milligrams per 5 milliliters of the excipient base. More preferably, ibuprofen is present in amounts of almost 100 milligrams per 5 milliliters of the excipient base.

Naproxen can be present in amounts of almost 50 to almost 250 milligrams per 5 milliliters of the excipient base. Preferably, it is present in amounts between almost 100 and almost 150 milligrams per 5 milliliters of the excipient base.

Other excipients that polyethylene glycol and sodium carboxymethyl cellulose useful in the practice of the present invention are those known to the art. These include humectants such as glycerin and propylene glycol, preservatives such as sodium benzoate and paraben, sweeteners such as sodium saccharin solutions, corn syrup and sorbitol, menthol and various coloring and flavoring agents.

Although not desired, it is believed that normally the solid polyethylene glycol when dissolved and mixed with the propylene glycol, serves to solubilize the active ingredient and inhibits this crystallization at room temperature.

The invention will now be determined with respect to the following exemplary examples.

Example 1 The formulation of the invention fixed below, was prepared in accordance with the following procedure. The example illustrates a formulation containing 200 milligrams of guaifenesin per 5 ml of formulation, twice the normal amount, which has an acceptable taste.

The PEG 1450 is introduced into a flask and melted to - fifty - . 50-60 ° C and 62.5 ml of propylene glycol are added with stirring. Guaifenasine, then dextromethorphan HBr and pseudoephedrine HC1 were dissolved in the mixture. In a separate flask, sodium CMC was dispersed in glycerin, and in a third flask, sodium benzoate and sodium saccharin were dissolved in 60 ml of purified water. The CMC sodium dispersion was added to the third flask and stirred for at least 30 minutes or until the preparation became thick. The preparation is weight was added to the bottle of the first flask. Then the sorbitol solution and the corn syrup with continuous stirring were added to the first flask. Then the menthol was dissolved in -12.5 ml of propylene glycol and added to the volume. The citric acid was dissolved in 10 ml of water and added to the volume. - The flavors and dyes were added and then the purified water has 500 ml. The resulting formulation has a pH of 3.38, 3.40, a viscosity of eJe # 3 at 10 RPM of 590 c.p.s and an axle viscosity at 50 rpm. of 534 cps. The proportion of polyethylene glycol against sodium carboxymethyl cellulose is 20: 1. The formulation has an acceptable flavor and aroma.

Example 2 The formulation of this example has the same proportions of medicines and polyethylene glycol as in the previous example but only one fifth as much sodium CMC.

The procedure for this formulation was essentially the same as in the previous example except that the pseudoephedrine HC1 was added with the citric acid dissolved in water and the dye was added separately dissolved in water.

The resulting formulation has a pH of 3,509, a viscosity of # 1 at 10 RPM from 236 - 256 cps. and an axis viscosity of 243-248 cps. at 20 RPM. The proportion of polyethylene glycol against sodium carboxymethyl cellulose is -100: 1. The formulation has an acceptable taste.

Example 3 In this formulation only 2 medicines are used, guaiefenasin and dextromethorphan HBr.

The procedure for this formulation was essentially the same as in Example 2. The resulting formulation has a pH of 3.45, 3.51, a viscosity of # 1 at 10 RPM of 177 cps. and an axle viscosity at 20 RPM of 178 cps. which increases to 210 - cps. at both RPM of 10 RPM and 20 RPM in 24 hours. The ratio of polyethylene glycol against sodium carboxymethyl cellulose is 100: 1. The formulation has an acceptable taste.

Example 4 This formulation was similar to Example 2, except that guaifenesin is 100 milligrams and the PEG content is 350 milligrams, and shows that the PEG content can be coordinated with the CMC sodium content to achieve the appropriate viscosity.

The procedure for this formulation was essentially the same as in the previous example, except that pseii doephedrine was dissolved with citric acid in water. The resulting formulation has a pH of 3.40, a viscosity of # 1 at 10 RPM of 101 cps. and a viscosity - from # 1 to 20 RPM of 102 cps. The ratio of polyethylene glycol to sodium carboxymethyl cellulose is 70: 1.

Example 5 In this formulation it is similar to example 2 only that 100 milligrams of guaifenesin was used, the polyethylene glycol was reduced to 350 milligrams and the sodium CMC was increased to 12.5 milligrams.

The procedure for this formulation was essentially the same as Example 4. The resulting formulation has a pH of 3.49, a viscosity of axis # 1 at 10 RPM of 176 cps and a viscosity of the shaft at 20 RPM of 174 cps. The ratio of polyethylene glycol COJI to sodium carboxymethyl cellulose is 28: 1.

The formulation has an acceptable taste Example 6 In this experiment, the amount of guaifenasin was increased to 200 milligrams per 5 milliliters and the amount of the remaining other ingredients the same as in Example 5 The pH of the resulting formulation is 3.63 and the viscosity of the # 1 axis It is 363 cps. at 10 RPM and 357 cps. at 20 RPM. The flavor of the formulation was acceptable.

Example 7 In this formulation similar to example 3, only -100 milligrams of guaifenesin were used, the polyethylene glycol was reduced to 350 milligrams and the sodium CMC was increased to 12.5 milligrams.

The process for this formulation was essentially the same as in Example 3. The resulting formulation has a pH of 3.45, a viscosity of # 1 at 10 RPM of 202 cps. and an axle viscosity at 20 RPM of 197 cps. The ratio of polyethylene glycol to sodium carboxymethyl cellulose is 28: 1. The formulation has an acceptable taste.

Example 8 In this formulation acetaminophen is presented as the pharmaceutically active compound.

The PEG 1450 is introduced into a flask and melted at -50-60 ° C and 60 ml of the propylene glycol was added with stirring.

Then the acetaminophen was added and dissolved in the mixture. - In a separate flask, sodium CMC was dispersed in glycerin; and in a third flask, the sodium in the third flask was stirred-for almost 45 minutes or until the preparation became thick. The thick preparation was added to the bottle in the first flask (containing the acetaminophen). Then the sorbitol solution and the corn syrup with continuous agitation are added to the first flask. Then the menthol was dissolved in 15.0 ml of propylene glycol and added to the volume. The sweetener and the co-lorant were added and then purified water was added until the volume of the solution equaled 500 ml. The citric acid was dissolved in 10 ml of water, then added to the volume until the pH was almost 3.5.

The resulting formulation has a pH of 3.48, 3.56, a viscosity of # 3 at 10RPM of 234 cps. The ratio of polyethylene glycol against sodium carboxymethyl cellulose is 100: 1. The formulation has an acceptable aroma and flavor.

Example 9 The procedure of Example 8 was repeated, except that 20 * 0 grams of acetaminophen were used. This produces a composition containing 200 mg of acetaminophen per 5 ml of the composition. The resulting formulation has a pH of 3.45, 3.51, a viscosity of # 3 at 10 RPM of 256 cps. The ratio of polyethylene glycol to sodium carboxymethyl cellulose is 100: 1. The formulation has an acceptable aroma and flavor.

It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, it claims as a priority what is contained in the following.

Claims

1. A liquid excipient base which hides the pharmaceutically acceptable flavor for the administration of relatively large amounts of pharmaceutically active compounds of unpleasant tasting, characterized in that the liquid excipient base consists of (a) polyethylene glycol having a molecular weight of almost 950 to almost 2200 , and (b) a cellulosic compound, the viscosity of the axis of the liquid excipient bases are -between almost 150 and almost 1000 centipoises at 50 RPM and 150-1200 at 10 RPM.

2. The excipient base according to claim 1, characterized in that the polyethylene glycol has a molecular weight between 1400 and almost 1600.

3. The excipient base according to claim 1, characterized in that the weight ratio of the polyethylene glycol and the cellulosic compound is between almost 100: 1 and almost 20: 1.

4. The excipient base according to claim 1, characterized in that the cellulosic compound is selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, mixtures and salts thereof.

5. The excipient base according to claim 1, characterized in that the cellulosic compound is carboxymethyl]. sodium cellulose.

6. The excipient base according to claim 5, characterized in that the weight ratio of polyethylene glycol and sodium carboxymethylcellulose is between almost 100: 1 and almost 20: 1.

7. The excipient base according to claim 1, characterized in that it has a pH between almost 2.5 and almost 5.

8. A pharmaceutical composition characterized in that - consists of (i) a liquid excipient base consisting of (a) polyethylene glycol having a molecular weight of almost 950 to almost -2200, and (b) a cellulosic compound selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, mixtures and salts of the same, the viscosity of the axis of the liquid excipient base is between almost 150 and almost 1000 centipoise at 50 RPM and 150-1200 centipoises at 10 RPM, and (ii) at least one pharmaceutically active compound selected from the group consisting of chili-ti-thymine drugs, decongestants, antitussives, expectorants, non-steroidal t-inflammatory cholines (NSAIDs) and analgesic drugs.

9. The composition according to claim 8, characterized in that the pharmaceutically active compound is an antihystamine selected from the group consisting of chlorpheniramine, brompheniramine, dexchlorpheniramine, dexbrompheniramine, -triprolidine, diphenhydramine, doxylamine, tripelenamine, cipro heptatin, bromodiphenhydramine, fenindamina, pyrilamina and azata dina.

10. The composition according to claim 8, characterized in that the pharmaceutically active compound is a decongestant selected from the group consisting of the - ft-Pseudoephedrine HCl, the phenylpropanoamine and the. phenylephrine

11. The composition according to claim 10, characterized in that the pharmaceutically active compound is pseudoephedrine HCl in an amount of almost 10 to almost 60 milli grams per 5 milliliters of the excipient base.

12. The composition according to claim 11, characterized in that the pharmaceutically active compound is pseudoephedrine HCl in an amount of almost 15 to almost 30 thousand grams per 5 milliliters of the excipient base.

13. The composition according to claim 8, characterized in that the pharmaceutically active compound is an expectorant selected from the group consisting of hydrate-of otorptin, guaifenasin, potassium iodide, potassium citrate and potassium guaicolsulfonate.

14. The composition according to claim 13, characterized in that the expectorant is guaifenasine in an amount of up to almost 300 milligrams per 5 milliliters of the excipient ba.

15. The composition according to claim 14, characterized in that the guaifenesin is present in a quantity of almost 100 to almost 200 milligrams per 5 milliliters of excipient base.

16. The composition according to claim 8, characterized in that the pharmaceutically active compound is an antitussive selected from the group consisting of carami-phene, dextromethorphan HBr, codeine phosphate and codeine sulfate.

17. The composition according to claim 8, characterized in that the antitussive is dextromethorphan HBr - in an amount between almost 5 and almost 20 milligrams per 5 milliliters of the excipient base.

18. The composition according to claim 17, characterized in that the antitussive is dextromethorphan HBr -in an amount between almost 10 and almost 15 milligrams per 5 milliliters of the excipient base.

19. The composition according to claim 8, characterized in that the NSAID is selected from the group consisting of the propionic acid derivatives, chi-acetic acid derivatives, fenamic acid derivatives, bife-nylcarboxylic acid derivatives and oxicams.

20. The composition according to claim 19, characterized in that the NSAID is selected from the group consisting of, buprofen, ketoprofen and naproxen.

21. The composition according to claim 20, characterized in that the buprofen is present in an amount in the range of almost 50 to almost 150 milligrams per 5 milliliters of the excipient base.

22. The composition according to claim 21, characterized in that the buprofen is present in an amount in the range of almost 100 to almost 150 milligrams per 5 milliliters of the excipient base.

23. The composition according to claim 20, characterized in that the naproxen is present in an amount - in the range of almost 50 to almost 250 milligrams per 5 milliliters - of the excipient base.

24. The composition according to claim 23, characterized in that the naproxen is present in an amount in the range of almost 100 to almost 150 milligrams per 5 milliliters of the excipient base.

25. The composition according to claim 8, characterized in that the analgesic is acetaminophen.

26. The composition according to claim 25, characterized in that the acetaminophen is present in an amount of almost up to 200 milligrams per 5 milliliters of the excipient ba.

27. The composition according to claim 26, characterized in that the acetaminophen is present in an amount of almost 150 to almost 175 milligrams per 5 milliliters of the excipient ba.

28. A method for concealing the taste of unpleasant tasting, characterized in that the at least one pharmaceutically active compound consists in dissolving such compound in a liquid exipient base consisting of polyethylene glycol having a molecular weight of almost 950 to almost 2200 and a cellulosic compound selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, mixtures and salts thereof, the viscosity of the liquid excipient bases are between almost 150 and almost 1000 centipoises at 50 RPM and 150-1200 centipoises at 10 RPM.

29. The method according to claim 28, characterized in that the polyethylene glycol has a molecular weight between 1400 and almost 1600.

30. The method according to claim 28, characterized in that the weight ratio of polyethylene glycol and the cellulose conical is between almost 100: 1 and almost 20: 1.

31. The method according to claim 28, characterized in that the cellulosic compound is sodium carboxymethylcellulose.

32. The method according to claim 31, characterized in that the weight ratio of polyethylene glycol and sodium carboxymethylcellulose is between almost 100: 1 and almost 20: 1.

33. The method according to claim 28, characterized in that the bese excipient has a pH between almost 2.5 - and almost 5.

34. The method according to claim 28, characterized in that the pharmaceutically active compound is selected from the group consisting of antihistaminic drugs, decongestants, antitussives, expectorants, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesic drugs.

35. The method according to claim 28, characterized in that the active compound is an antihistamine selected from the group consisting of chlorpheniramine, dexbrompheniramine, triprolidine, diphenhydramine, doxylamine, tripelannamine, -ciproheptatin, bromodiphenhydramine, phenindamine, pyrilamine and azatadine.

36. The method according to claim 28, characterized in that the pharmaceutically active compound is a de-congener selected from the group consisting of the pseudo-ephedrine HCl, phenylpropanolamine and phenylephrine.

37. The method according to claim 36, characterized in that the compound pharmaceutically is the pseudoephedrine HCl in an amount of almost 10 to almost 60 milligrams per 5 milliliters of the excipient base

38. The method according to claim 37, characterized in that the pharmaceutically active compound is pseudoephedrine HCl in an amount of almost 15 to almost 30 milligrams per 5 milliliters of the excipient base.

39. The method according to claim 28, characterized in that the pharmaceutically active compound is an expectorant selected from the group consisting of oter pina hydrate, guaifenesin, potassium iodide, potassium citrate and potassium guaicolsulfonate.

40. The method according to claim 39, characterized in that the expectorant is guaifenacin in an amount up to almost 300 milligrams per 5 milliliters of the excipient base.

41. The method according to claim 40, characterized in that the guaifenesin is present in an amount of almost 100 to almost 200 milligrams per 5 milliliters of the excipient base.

42. The method according to claim 28, char This is because the pharmaceutically active compound is an antitussive selected from the group consisting of caramiphen, -dextromethorphan HBr, codeine phosphate and codeine sulfate.

43. The method according to claim 42, characterized in that the antitussive is dextromethorphan HBr in an amount between almost 5 and almost 20 milligrams per 5 milliliters of the excipient base.

44. The method according to claim 42, characterized in that the antitussive is dextromethorphan HBr in an amount between almost 10 and almost 15 milligrams per 5 milliliters of the excipient base.

45. The method according to claim 28, characterized in that the NSAID is selected from the group consisting of propionic acid derivatives, acetic acid derivatives, fenamic acid derivatives, biphenylcarboxylic acid derivatives and oxicams.

46. The method according to claim 45, characterized in that the NSAID is selected from the group consisting of kotoprofen, buprofen and naproxen.

47. The method according to claim 46, characterized in that the ibuprofen is present in an amount in the range of almost 50 to almost 150 milligrams per 5 milliliters of the excipient base.

48. The method according to claim 46, characterized in that the buprofen is present in an amount in the range of almost 100 to almost 150 milligrams per 5 milliliters of the excipient base.

49. The method according to claim 46, characterized in that the naproxen is present in an amount in the range of almost 50 to almost 250 milligrams per 5 milliliters of the excipient base.

50. The method according to claim 49, characterized in that the naproxen is present in an amount in the range of almost 100 to almost 150 milligrams per 5 milliliters of the excipient base.

51. The method according to claim 28, characterized in that the analgesic is acetaminophen.

52, The method according to claim 51, characterized in that the acetaminophen is present in an amount - up to almost 200 milligrams per 5 milliliters of the excipient base.

53. The method according to claim 51, characterized in that the acetaminophen is present in an amount of almost 150 to almost 175 milligrams per 5 milliliters of the excipient base.