JPH04295422A - Noneffervescent ibuprofen composition - Google Patents

Abstract

PURPOSE: To make the unpleasant taste of water-soluble ibuprofen salts in aqueous solutions. CONSTITUTION: The unpleasant taste of water-soluble ibuprofen salts in an aqueous solution is masked by incorporating in the solution a taste-masking amount of an alkali metal bicarbonate, alkali metal monohydrogen phosphate or alkali metal tribasic citrate. The taste-masking compound is preferably the alkali metal bicarbonate, especially preferably sodium bicarbonate.

Description

Description: FIELD OF THE INVENTION This invention relates to non-foaming water-soluble compositions containing ibuprofen in the form of a water-soluble salt. In particular, the present invention provides non-foaming water-soluble compositions of water-soluble ibuprofen salts that mask the unpleasant taste of the salt. [Prior art and its problems] Ibuprofen [namely, 2
-(4-isobutylphenyl)propionic acid] is
It is well known as a therapeutic agent with analgesic, anti-inflammatory and antipyretic effects. Ibuprofen is widely used as an alternative to aspirin (i.e. acetylsalicylic acid) and paracetamol (i.e. acetaminophen) in the treatment of pain such as headaches and toothaches, especially when accompanied by inflammation, e.g. in rheumatic diseases. . However, ibuprofen is insoluble in water and gastric irritation often occurs when administered in solid or suspended form, especially in doses required for the treatment of rheumatism. Only a small amount of salt in ibuprofen is water-soluble.
This includes alkali metal salts and amino acid salts. However, aqueous solutions of water-soluble ibuprofen salts have an unpleasant burning taste, and for that reason their use has generally been avoided. Many attempts have been made to improve the solubility and taste of ibuprofen, particularly in its free acid form. According to British Patent Application No. 2189994, the low water solubility of ibuprofen is 9-17% by weight of ibuprofen; 17-33% by weight of arginine;
or arginine containing up to 40% by weight of lysine/
It has been disclosed that this can be overcome by formulating an effervescent composition consisting of a lysine mixture; 20-35% by weight of sodium or potassium bicarbonate; and 25-40% by weight of sodium or potassium hydrogentartrate. The presence of arginine is essential and it appears that ibuprofen needs to be present as the free acid. In particular, it is stated that the arginine and lysine salts of ibuprofen cannot be used because they do not result in complete dissolution of ibuprofen. No other ibuprofen salts are mentioned. European Patent Application No. 0203768 discloses effervescent compositions of pre-blended mixtures of particulate therapeutic agents and effervescent system components. The therapeutic agent should have a particle size of 100 to 600 micrometers, and the effervescent system components should have a particle size of 50 to 600 micrometers.
A particle size of ~600 micrometers is required. Ibuprofen is among the many identified therapeutic agents, and sodium bicarbonate, potassium bicarbonate and ammonium bicarbonate are among the effervescent system components identified. However, there are no examples of compositions containing ibuprofen, and no mention of the use of ibuprofen salts. European Patent Application No. 0228164 discloses effervescent ibuprofen-containing compositions which, when added to water, improve the suspension of ibuprofen or its salts. The composition includes a pharmaceutically acceptable surfactant and a pharmaceutically acceptable water-insoluble hydrophilic polymer. Exemplary polymers include starch and its derivatives, cellulose and its derivatives; cross-linked polyvinylpyrrolidone and alginic acid. Suitable polymers include microcrystalline cellulose and croscarmellose.
It is sodium. Identified effervescent couple base components include sodium bicarbonate and potassium bicarbonate. The amounts of the components of the effervescent couple are generally selected such that the pH of the resulting aqueous suspension is less than 7.0, preferably between 3.0 and 4.0. Although free ibuprofen is said to be preferred, the use of sodium or potassium salts is mentioned. When ibuprofen is in such a water-soluble salt form, the salt reacts with the acid component of the effervescent couple, causing precipitation of ibuprofen when the composition is added to water. British Patent Application No. 2193093 discloses that 33-46% by weight of free ibuprofen, 34-51%
Water soluble ibuprofen compositions containing % L-arginine and 9-29% sodium bicarbonate by weight are disclosed. The molar ratio of L-arginine to ibuprofen should be in the range of 1.1:1 to 1.5:1, and the weight ratio of sodium bicarbonate to ibuprofen should be in the range of 0.25:1 to 0.75:1. It is necessary to be within the range of In recognition of the prior art, UK Patent Application No. 2193093 mentions the good water solubility of ibuprofen sodium, but states not to use this salt in oral formulations. In particular, it is stated that: “Ibuprofen sodium salt is one of the rare salts that is highly soluble in water, but it is not well suited for oral formulations because it produces solutions with pH that is harmful to the gastrointestinal tract.” Example 13 of UK Patent Application No. 2193093 describes Arginine Ibuprofen (37% by weight)
), sodium bicarbonate (10% by weight) and sucrose (46% by weight). The molar ratio of sodium bicarbonate to arginine ibuprofen is 1.2:1. When the granules dissolve in water, insoluble ibuprofen is formed;
The result is a formulation that is described as unacceptable both in taste and local tolerability. [0009] Japanese Patent Publication No. 63-198620 discloses non-effervescent ibuprofen compositions containing antacids and/or mucosal protectants to reduce the risk of gastrointestinal disorders. Identified antacids and/or mucosal protectants include sodium bicarbonate, although there are no examples of compositions containing sodium bicarbonate. Furthermore, there is no mention of using ibuprofen salt or masking the taste of ibuprofen. WO 89/03210 discloses that by dispersing and suspending or dissolving ibuprofen or a salt or ester thereof in an aqueous medium containing a methylcellulose composition, a transparent, stable and
It is disclosed that a palatable liquid ibuprofen composition is obtained. Flavoring agents, particularly sweeteners, can be present to mask the bitter taste of ibuprofen. optionally bicarbonate,
Potassium bicarbonate is preferably present in the aqueous medium to aid in dispersing the ibuprofen. Flavoring agents, preferably sucrose, can be added to mask the taste of ibuprofen. There is no mention of using bicarbonate with ibuprofen salts or of non-aqueous formulations containing both ibuprofen and bicarbonate. In the compositions of the Examples, the amount of sucrose is about four times the amount of potassium bicarbonate by weight, except for the composition of Example 6, which does not contain bicarbonate. The molar ratio of bicarbonate to ibuprofen was 1.2 (Examples 1, 4 and 5), 4.7 (Example 3) and 1
9.0 (Example 2). It has been surprisingly discovered that the inclusion of a sufficient amount of sodium bicarbonate in a non-foaming water-soluble composition containing a water-soluble ibuprofen salt masks the taste of ibuprofen in an aqueous solution of the composition. It was done. Additionally, it was discovered that potassium bicarbonate can be used as a substitute for sodium bicarbonate, but ammonium bicarbonate cannot. It was also found that the corresponding monohydrogen phosphate and tribasic citrates had a similar, but weaker effect in masking taste. In a first aspect of the invention, the composition comprises an alkali metal bicarbonate, an alkali metal monohydrogen phosphate, in an amount sufficient to mask the taste of ibuprofen salt in an aqueous solution of the composition. A non-foaming water-soluble composition comprising a water-soluble ibuprofen salt is provided, characterized in that it contains a taste-masking compound selected from salts and alkali metal tribasic citrates. In a second aspect, the present invention provides for the use of alkali metal bicarbonates, alkali metal monohydrogen phosphates, and alkali metal tribasic citrates to mask the taste in aqueous solutions of water-soluble ibuprofen salts. Provide usage. In a third aspect, the present invention provides a method for adding a taste-masking compound selected from alkali metal bicarbonates, alkali metal monohydrogen phosphates, and alkali metal tribasic citrates to a solution in a taste-masking amount. To provide a method of masking the taste of water-soluble ibuprofen salt in an aqueous solution by mixing the salt into the water-soluble ibuprofen salt. Normally, ibuprofen will be the potassium salt, preferably the sodium salt, although other water-soluble ibuprofen salts such as amino acids such as arginine or lysine can also be used. If necessary, the salt can be formed in aqueous solution. Alkali metal bicarbonates are much more desirable as taste-masking compounds. Alkali metal monohydrogen phosphates and especially tribasic citrates also have a significant effect on taste masking. However, alkali metal monobasic and dibasic citrates and alkali metal dihydrogen phosphates are unsatisfactory because their pKa values are too low, leading to precipitation of ibuprofen from aqueous solutions of water-soluble ibuprofen salts. do not have. Alkali metal carbonates and tribasic phosphates, in potentially taste-masking amounts,
The resulting aqueous solution has an unacceptably high pH for oral administration and cannot be used. Usually, the alkali metal anion of the taste-masking compound is potassium, preferably sodium. “Alkali metals” as applied to taste-masking compounds in the context of this application
The term does not include ammonium. The use of ammonium bicarbonate produces an unpalatable aqueous solution. The amount of taste-masking compound required will depend on the amount of ibuprofen salt present in the composition and the taste-masking extent of the salt. Typically, the taste masking compound will be present in excess by weight of the ibuprofen salt calculated as free ibuprofen. For taste masking with bicarbonate, the molar ratio of bicarbonate to ibuprofen salt is suitably between 1:4 and 12:1. The molar ratio is preferably between 3:4 and 9:1, particularly between 4:1 and 9:1 for sodium bicarbonate and between 3:4 and 9:2 for potassium bicarbonate. In the case of taste masking with alkali metal monohydrogen phosphate, the molar ratio of monohydrogen phosphate to ibuprofen salt is suitably between 3:4 and 7:1. The molar ratio is
The ratio is preferably between 5:2 and 6:1, particularly 5:2 and 5:1 for disodium salts and 7:2 and 6:1 for dipotassium salts. For taste masking with alkali metal tribasic citrate, the molar ratio of tribasic citrate to ibuprofen salt is 1
A ratio between :3 and 3:1 is suitable. The molar ratio is 2
:3 to 4:3 is desirable, particularly 3:4 to 4:3 for trisodium salts, and 2:3 to 4:3 for tripotassium salts. The compositions of the present invention will normally take the form of a flowable powder suitably packed into unit dose sachets. However, the composition may also be in some other form, such as a water-soluble tablet suitable for dissolution in water or syrup. In the case of solid water-soluble preparations such as tablets, small amounts of effervescent couples can be included in the composition to aid in dispersion of the tablet when added to water. This amount of effervescent couple is well below the amount required for the composition to be classified as an effervescent composition in which sustained and substantial release of carbon dioxide occurs. The composition includes
Also, conventional sweeteners such as aspartame and/or cyclamate, disintegrants, glidants, lubricants, and bulking agents such as fructose, sorbitol, starch dextrate or sucrose may be used. It can contain additives. A unit dose of the composition of the invention will normally contain an amount of ibuprofen salt equivalent to a conventional oral unit dose of ibuprofen, ie usually 200 or 400 mg (calculated on free ibuprofen). EXAMPLES The invention is illustrated by the following non-limiting examples. In these examples, the sodium ibuprofen used was the dihydrate salt (molecular weight 264.3) and therefore 512 mg of this salt was equivalent to 400 mg of ibuprofen.
Corresponds to g. Example 1 A non-foaming dry powder sodium ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing the equivalent of 400 mg of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Sodium Ibuprofen
512mg 19.7%
Active compound sodium bicarbonate
700mg 26.9%
change of taste

(and buffer) dextrose 1,300mg
50.0% Bulk agent Sodium Saccharin 50
mg 1.9% Sweetener Black Currant Flavoring Agent 40
mg 1.5% flavoring agent total
2,602mg 100.0
% (molar ratio of taste masking compound: ibuprofen salt =
4.3:1) [0024] The contents of each sachet are 1
The unpleasant taste and burning sensation normally associated with sodium ibuprofen were virtually undetectable by most patients in the resulting solution. Example 2 The procedure of Example 1 was repeated except that only 500 mg/sachet of sodium bicarbonate was used and the amount of dextrose was reduced to 1,500 mg/sachet to compensate for this reduction. (The molar ratio of taste masking compound: ibuprofen salt is 3.1:1). In this case, the resulting aqueous solution was not as acceptable as that of Example 1, but was a significant improvement over the composition without sodium bicarbonate. Although the unpleasant taste was mostly eliminated, the burning sensation was still detectable. Example 3 A non-foaming dry powder sodium ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing 200 mg equivalents of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Sodium Ibuprofen
256mg 15.5%
Active compound sodium bicarbonate
700mg 42.
4% taste change

(and buffer)
dextrose 65
0mg 39.4%
Bulk agent sodium saccharin
25mg 1.5%
sweetener black currant flavoring agent
20mg 1.2%
Flavoring agent total
1,651mg 10
0.0% (molar ratio of taste masking compound: ibuprofen salt = 8.6:1) The contents of each sachet are:
Easily soluble in 100ml of water, the unpleasant taste and burning sensation normally associated with sodium ibuprofen is
Virtually undetectable by most patients in the resulting solution. Example 4 The procedure of Example 3 was repeated except that only 350 mg/sachet of sodium bicarbonate was used (the molar ratio of taste masking compound: ibuprofen salt was 4.3:1). . The resulting aqueous solution had exactly the same taste as that of Example 3. That is, the burning sensation normally associated with sodium ibuprofen was virtually undetectable by most patients. Example 5 A non-foaming dry powder sodium ibuprofen formulation was prepared as in Example 1, but containing amounts of sodium bicarbonate of 0, 81, 114, 175, 35
0, 525, 700, 1,000, 1,400
and 2,000 mg/sachet. (Molar ratio of taste-masking compound: ibuprofen salt = 0:1, 0, respectively)
．． 5:1, 0.7:1, 1.1:1, 2.2
:1, 3.2 :1, 4.3 :1, 6.1
:1, 8.6:1 and 12.3:1) 003
1) The contents of each sachet were easily dissolved in 100 ml of water. Taste the resulting solutions and choose the one with the lowest added sodium bicarbonate level (i.e. 81m
g/sachet) did not completely mask the burning taste. Furthermore, the highest level (i.e. 2,000 m
g/sachet) while masking the taste of ibuprofen salts, produced an unacceptable taste on its own. Optimal taste masking was achieved when bicarbonate was added at 700 or 1,000 mg/sachet. Example 6 A non-foaming dry powder sodium ibuprofen formulation was prepared as in Example 1, but instead of sodium carbonate, 19, 58, 97, 136, 194, 42
7, 621, 834, 1,183, 1,668
and 2,385 mg/sachet of potassium bicarbonate. (Molar ratio of taste-masking compound: ibuprofen salt = 0.1:1, 0.3:1, 0.5:1, respectively)
, 0.7:1, 1.0:1, 2.2:1
, 3.2:1, 4.3:1, 6.1:1,
8.6:1 and 12.3:1) The contents of each sachet were easily dissolved in 100 ml of water. Taste the resulting solution and
The one with the lowest added potassium bicarbonate level (i.e.
19 mg/sachet) did not mask the burning taste. Furthermore, the highest level (i.e. 1,668 mg
/ sachets and above) masked the taste of ibuprofen salts, but provided an unacceptable taste on its own. Optimal taste masking was achieved at levels between 136 mg/sachet and 834 mg/sachet. Comparative Example 7 A non-foaming dry powder sodium ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing 400 mg equivalents of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Sodium Ibuprofen
512mg 20.0%
Active compound ammonium bicarbonate
656mg 25.6%
taste change

(and buffer) dextrose 1,300m
g 50.8% Bulk agent Sodium Saccharin 50
mg 2.0% Sweetener black currant flavoring agent 40
mg 1.6% flavoring agent total
2,558mg 100.0
% 0036 Contents of each sachet is 100ml
easily dissolved in water. However, ammonium bicarbonate gave the aqueous solution an unpleasant taste. Example 8 A non-foaming dry powder sodium ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing the equivalent of 400 mg of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Sodium Ibuprofen
512mg 16.0%
Active compound trisodium citrate
600mg 18.
7% taste change (dihydrate)

(and buffer) dextrose 2,000mg
62.5% bulking agent sodium saccharin 50mg
1.6% sweetener black currant flavoring agent 40mg
1.2% flavoring agent
Total 3
,202mg 100.0%(
Taste masking compound: ibuprofen salt molar ratio = 1.1:
1) 0039] The content of each sachet is 100ml.
The unpleasant taste normally associated with sodium ibuprofen was virtually undetectable by most patients in the resulting solution. However, a slight burning sensation remained. Comparative Example 9 The procedure of Example 8 was repeated, but using either 1,091 mg of disodium citrate or 1,079 mg of monosodium citrate. However, when the contents of the sachets were added to 100 ml of water, ibuprofen precipitated in both cases. Example 10 A non-foaming dry powder sodium ibuprofen formulation was prepared in the same manner as in Example 8, except that the amount of trisodium citrate contained was 200, 400, 600.
, 800 , 1,200 , 1,700 , 2,40
0 and 3,400 mg/sachet. Dihydrate citrate was used. (Molar ratio of taste masking compound: ibuprofen salt = 0.4:1, 0.7:1, respectively,
1.1:1, 1.4:1, 2.1:1, 3
．． 0:1, 4.2:1 and 6.0:1) The contents of each sachet were easily dissolved in 100 ml of water. Taste the resulting solution and
The one with the lowest level of added citric acid (i.e. 200
mg/sachet) did not mask the burning taste. Additionally, the highest level (i.e., 3,400 mg/sachet), while masking the taste of ibuprofen salt, produced an unacceptable taste on its own. Optimal taste masking was achieved when citric acid was added at 400 or 600 mg/sachet. Example 11 A non-foaming dry powder sodium ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing the equivalent of 400 mg of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Sodium Ibuprofen
512mg 19.7%
Active compound sodium monohydrogen phosphate
700mg 26.9%
Change flavor (anhydrous)

(and buffer) dextrose 1,300mg
50.0% Bulk agent Sodium Saccharin 50mg
1.9% sweetener black currant flavoring agent 40mg
1.5% flavoring agent
total
2,602mg 1
00.0% (molar ratio of taste masking compound: ibuprofen salt = 2.5:1) The contents of each sachet are easily soluble in 100 ml of water and the unpleasant taste normally associated with sodium ibuprofen is eliminated. Virtually undetectable by most patients in the resulting solution. Example 12 A non-foaming dry powder sodium ibuprofen preparation was prepared in the same manner as in Example 11, but the amount of sodium monohydrogen phosphate contained was 250, 500, 750.
, 1,000, 1,500, and 2,000 mg
/I changed it to a sachet. Anhydrous phosphate was used. (Molar ratio of taste masking compound: ibuprofen salt = 0.9 each
:1, 1.8:1, 2.7:1, 3.6:
1, 5.5:1, and 7.3:1) The contents of each sachet were easily dissolved in 100 ml of water. Taste the resulting solution and
The one with the lowest level of added phosphoric acid (i.e. 250
mg/sachet) did not mask the burning taste. Additionally, the highest level (i.e., 2,000 mg/sachet) while masking the taste of ibuprofen salts produced an unacceptable taste on its own. Optimal taste masking was achieved when phosphoric acid was added at 750 or 1,000 mg/sachet. Comparative Example 13 The procedure of Example 11 was repeated, except that 650 mg
of monosodium dihydrogen phosphate was used. Ibuprofen precipitated when the contents of the sachet were added to 100 ml of water. Comparative Example 14 Example 11 using 700 mg of trisodium phosphate
The procedure was repeated, but the pH (12.1) was at a level considered to be at risk of harming the mucous membranes of the mouth (approximately 1
0.5), so the resulting solution was tasteless. Corresponding compositions containing sodium or potassium carbonate and sodium, potassium or ammonium hydroxide were also not tasted due to the high pH of the resulting aqueous solutions. Furthermore,
Relevant data for these compositions are as follows. [0051] Salt
mg/sachet
pH of solution Sodium carbonate
440mg
10.7 Potassium carbonate 572mg
10.9
Sodium hydroxide 332m
g12.1
potassium hydroxide
465mg 12
．． 8 Ammonium hydroxide
530mg
11.2 In contrast to the above, Example 1,
The resulting solutions of 6, 7, 8 and 11 had the following pHs: Example 15 A non-foaming dry powder lysine ibuprofen formulation was
The following ingredients were mixed and this mixture was further filled into sachets containing the equivalent of 400 mg free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Lysine Ibuprofen
690mg 24.8%
Active compound sodium bicarbonate
700mg 2
5.2% Change in taste

(and buffer) dextrose 1,
300mg 46.8%
Bulk agent sodium saccharin
50mg 1.8%
sweetener black currant flavoring agent
40mg 1.4%
Flavoring agent total
2,780mg
100.0% (molar ratio of taste masking compound: ibuprofen salt = 4.3:1) 0056
The contents of each sachet are easily dissolved in 100ml of water and
The unpleasant taste normally associated with lysine ibuprofen was virtually undetectable by most patients in the resulting solution. Sodium bicarbonate thus effectively masked the burning sensation caused by lysine ibuprofen. Comparative Example 16 Non-foaming dry powder lysine ibuprofen formulation was
The following ingredients were mixed and this mixture was further filled into sachets containing the equivalent of 400 mg free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Lysine Ibuprofen
690mg 33.2%
Active compound dextrose
1,300mg 62
．． 5% bulking agent sodium saccharin 50mg
2.4% sweetener black currant flavoring agent
40mg
1.9% flavoring agent
Total 2,080
mg 100.0% 0059
The contents of each sachet easily dissolved in 100 ml of water. Lysine ibuprofen was completely dissolved in water. When I tasted it, the solution was strong and a little delayed (20-30 seconds).
It caused a burning sensation. Example 17 A taste test was conducted using 39 volunteers in a double-blind, fully randomized crossover experiment. Each volunteer was asked to drink 50 ml each of a control solution and a test solution of the following composition. Ingredients
Contrast
test
mg/50ml
mg/50ml
sodium ibuprofen 2
56mg 256
mg sodium bicarbonate
0mg
350mg dextrose
1,000mg
650mg Sodium Saccharin 25m
g 25mg
Black currant flavoring agent
20mg
20 mg (molar ratio of taste-masking compound: ibuprofen salt was 0 for the control solution and 4.3:1 for the test solution). Two of the volunteers
0 volunteers were given the control sample first and the remaining 19 volunteers were given the test sample first. The order of presentation was random, and neither volunteers nor test supervisors knew the identity of the samples. Two of the volunteers who were initially given the control sample found the taste so unpleasant that they did not wish to continue testing, so data from these volunteers was not used. Volunteers rated the following parameters regarding the taste of each sample, and their ratings ranged from 0 to 1.
They were asked to mark on a 24 mm visual analogue scale. (a) taste when drinking; (b) aftertaste; and (c) overall acceptability of the product. For parameters (a) and (b), volunteers were asked to evaluate taste and taste rather than subjective reactions to sensation. They were instructed to record only the intensity of the aftertaste sensation. The subjective response to the product is determined by the parameter (c
) was recorded independently. The t-test results for each parameter were as follows. Parameter t
Probability 95% Confidence interval (a)
-2.97 0.005
-20.8±14.2
(b) -3.86
0.0005 -20.8±1
0.9 (c)
2.98 0.005
18.8±12.8 0067
] There was some variation in the records depending on whether the control sample was taken first or the test sample first. However, as can be seen from the related data listed in Table 1 below, the dependence on order was significant only for the taste when drunk. It is clear from the taste test results reported above that the addition of sodium bicarbonate to the sodium ibuprofen control solution led to a significant improvement in the taste and overall acceptability of the product. It is particularly important to note that the perceived aftertaste intensity was reduced. [Table 1] Control sample first Test sample Control test difference Control test difference (a) Taste when drinking Average 51.4
45.6 - 5.5 80.7
45.6 -31.5
Standard deviation 34.4 30.5
20.5 28.0(
b) Aftertaste average 48.7
28.9 -19.8 61.9
40.3 -21.6
Standard deviation 33.7 20.6
28.3 34.1 (c
) Overall tolerance average 83.9
94.3 10.4 60.1
86.7 26.6
Standard deviation 28.4 21.0
33.8 26.2
Example 18 A non-foaming dry powder arginine ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing the equivalent of 400 mg of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Arginine Ibuprofen
738mg 26.1%
Active compound sodium bicarbonate
700mg 24.7%
change of taste

(and buffer) dextrose 1,300m
g 46.0% Bulk agent Sodium Saccharin 5
0mg 1.8% Sweetener Black Currant Flavoring Agent 4
0mg 1.4% Flavoring agent total
2,828mg 100.
0% (molar ratio of taste masking compound: ibuprofen salt = 4
．． 3:1) [0071] The contents of each sachet are 10
Easily soluble in 0 ml of water, the unpleasant taste normally associated with arginine ibuprofen was virtually undetectable by most patients in the resulting solution. in this way,
Sodium bicarbonate effectively masked the burning sensation caused by arginine ibuprofen. Comparative Example 19 A non-foaming dry powder arginine ibuprofen formulation was prepared by mixing the following ingredients and filling the mixture into sachets containing 400 mg equivalents of free ibuprofen: Ingredients
mg/sachet % W/W
Purpose Arginine Ibuprofen
738mg 34.7%
Active compound dextrose
1,300mg 61
．． 6% bulking agent sodium saccharin 50mg
2.3% sweetener black currant flavoring agent
40mg 1
．． 9% Flavoring agent total
2,128mg
100.0% The contents of each sachet were easily dissolved in 100 ml of water. Arginine ibuprofen was completely soluble in water. In taste, the solution produced a strong, slightly delayed and significant burning sensation. Example 20 A non-foaming dry powder sodium ibuprofen formulation was prepared as in Example 8, but instead of trisodium citrate, 125, 251, 440, 6
91, 880, 1,320, 1,885, 2,
639 and 3,771 mg/sachet of potassium citrate monohydrate were used. (Molar ratio of taste masking compound: ibuprofen salt = 0.2:1, 0.4:
1, 0.7:1, 1.1:1, 1.4:1
, 2.1:1, 3.0:1, 4.2:1 and 6.0:1
) The contents of each sachet were easily dissolved in 100 ml of water. Taste the resulting solution and
The one with the lowest added citric acid level (i.e. 125
mg/sachet) did not mask the burning taste. Additionally, the highest levels (i.e., 1,885 mg/sachet or higher) mask the taste of ibuprofen salts while
Brought on its own an unacceptable taste. Optimal taste masking was achieved when citric acid was added at levels between 440 and 1,320 mg/sachet. Example 21 A non-foaming dry powder sodium ibuprofen formulation was prepared as in Example 11, but instead of sodium monohydrogen phosphate, 101, 169, 304, 60
7, 911, 1,215, 1,822 and 2,
463 mg/sachet of potassium monohydrogen phosphate was used. (Molar ratio of taste masking compound: ibuprofen salt = 0.3:1, 0.5:1, 0.9:1, 1, respectively)
．． 8:1, 2.7:1, 3.6:1, 5.
4:1 and 7.3:1) The contents of each sachet were easily dissolved in 100 ml of water. Upon tasting the resulting solution, the lowest level of phosphoric acid added (ie, 101 mg/sachet) did not mask the burning taste. Additionally, the highest level (i.e., 2,000 mg/sachet) while masking the taste of ibuprofen salts produced an unacceptable taste on its own. The one that best concealed the taste was 1,215.
and 1,822 mg/sachet.

Claims (16)

[Claims] Claim 1: selected from alkali metal bicarbonates, alkali metal monohydrogen phosphates, and alkali metal tribasic citrates in an amount sufficient to mask the taste of ibuprofen salts when dissolved in water. A non-foaming water-soluble composition comprising a water-soluble ibuprofen salt, characterized in that it contains a taste-masking compound. 2. The composition of claim 1, wherein the taste-masking compound is an alkali metal bicarbonate. 3. A composition according to claim 1, wherein the taste masking compound is sodium bicarbonate, monosodium phosphate or trisodium citrate. 4. The composition of claim 3, wherein the taste-masking compound is sodium bicarbonate. 5. The composition according to claim 1, wherein the ibuprofen salt is an alkali metal ibuprofen salt. 6. The taste-masking compound is an alkali metal bicarbonate in a ratio of 1:4 to 1 to ibuprofen salt.
A composition according to any one of claims 1 to 5, present in a molar ratio of 2:1. 7. The composition of claim 6, wherein the alkali metal bicarbonate is present in a molar ratio of 3:4 to 9:1 to ibuprofen salt. 8. The taste-masking compound is an alkali metal monohydrogen phosphate, and the taste masking compound is 3:4 to ibuprofen salt.
6. A composition according to any one of claims 1, 3 and 5, present in a molar ratio of ~7:1. 9. The composition of claim 8, wherein the monohydrogen phosphate salt is present in a molar ratio of 5:2 to 6:1 to ibuprofen salt. 10. The taste-masking compound is an alkali metal tribasic citrate salt, which is 1:1 to ibuprofen salt.
6. A composition according to any one of claims 1, 3 and 5, present in a molar ratio of 3 to 3:1. 11. The composition of claim 10, wherein the tribasic citrate is present in a molar ratio of 2:3 to 4:3 to ibuprofen salt. 12. An aqueous solution obtained by dissolving the composition according to any one of the above claims in water. 13. Use of an alkali metal bicarbonate, alkali metal monohydrogen phosphate, or alkali metal tribasic citrate to mask the taste of a water-soluble ibuprofen compound in the non-effervescent aqueous solution. 14. Use according to claim 13, wherein the taste masking compound and/or the ibuprofen salt are defined in any one of claims 2 to 11. 15. A taste-masking amount of an alkali metal bicarbonate in a non-effervescent aqueous solution of a water-soluble ibuprofen salt.
A method of masking the taste of water-soluble ibuprofen salt in the solution by mixing an alkali metal monohydrogen phosphate or an alkali metal tribasic citrate. 16. A method according to claim 15, wherein the taste-masking compound and/or the ibuprofen salt are defined in any one of claims 2 to 11.