AU3825200A

AU3825200A - Drinkable pharmaceutical solution

Info

Publication number: AU3825200A
Application number: AU38252/00A
Authority: AU
Inventors: Emmanuel Guerin; Christophe Lebon; Pascal Suplie
Original assignee: Ethypharm SAS
Current assignee: Ethypharm SAS
Priority date: 1999-04-06
Filing date: 2000-04-06
Publication date: 2000-10-23
Anticipated expiration: 2020-04-06
Also published as: FR2791888B1; WO2000059468A1; HUP0200711A3; IL145768A0; AU778364B2; BR0009551A; FR2791888A1; EP1165043A1; HUP0200711A2; ZA200108116B; ZA200108206B; CN1351488A

Description

WO 00/59468 PCT/FROO/00870 "Oral pharmaceutical suspension" The present invention relates to an oral pharmaceutical composition intended for facilitated oral 5 administration. The oral administration of solid forms such as tablets can prove difficult or even dangerous for children and the elderly, who prefer chewable tablets, tablets which 10 dissolve in the mouth or in a spoon of water, granules, powders, solutions or suspensions. The active ingredients incorporated into these types of formulations sometimes have a bitter taste which 15 persists for a long time and which cannot be effectively masked by the addition of a sweetener or a flavoring. However, the taste and the aftertaste are important criteria for the acceptance of the medicament by the patient. 20 In the oral suspensions of bitter active ingredient already described in the prior art, the active ingredient is generally coated with a lipid substance, either directly or after incorporation into a core. The 25 lipid substances used are for example a partially hydrogenated vegetable oil (EP 670 722), stearic acid and/or palmitic acid (FR 2 615 101), glyceryl tripalmitate (EP 664 701), or a mixture of glyceryl monostearate and beeswax in the proportions 9/1 30 (EP 769 948). In WO 91/16043, the granules containing the active ingredient are coated with a polymer membrane which is soluble at a pH greater than or equal to 5. The 35 granules also contain 1 to 20% by weight of an acidic compound intended to reduce the dissolution of the membrane in the oral cavity.

- 2 Ibuprofen is an active ingredient with a bitter taste which has been the subject of numerous studies in order to formulate it in stable compositions in which its taste is masked. 5 A prior art solution consists in coating the ibuprofen containing granules with a polymer intended to mask its bitter taste. This polymer is for example a phthalate (WO 91/16043), a vinyl acetal (JP 91/83922), a 10 cellulose acetate phthalate (WO 95/05166) or a methacrylic acid copolymer (EP 524 180). The disadvantage of these formulations consists in the properties of the polymer used. Indeed, all the prior 15 art polymers used for masking the taste of ibuprofen causes the delayed release of the active ingredient, such that its dissolution profile is modified. Another prior art solution consists in preparing an 20 aqueous suspension of ibuprofen. This suspension contains either a lipid substance and a surfactant (WO 94/25006, US 5 110 606, WO 96/22762, WO 94/05260), or a suspending agent, such as a polysaccharide (JP 98/182 449), a mixture of cellulose and of xanthan 25 gum (EP 556 057), a mixture of polyethylene glycol and of sodium carboxymethyl cellulose (US 5 602 182), a mixture of xanthan gum and of pregelatinized starch (EP 405 930), a mixture of xanthan gum, of microcrystalline cellulose and of carboxymethyl 30 cellulose (EP 298 740). The subject of the present invention is an oral pharmaceutical suspension consisting of a liquid phase in which one or more solid active ingredients are 35 dispersed, characterized in that the soluble fraction of said active ingredient(s) in the liquid phase is less than 10% by weight, preferably 5% by weight, more preferably still 1% by weight relative to the weight of the suspension.

- 3 The active ingredient is in the form of crystals, preferably crystals of less than 500 microns in size, or formulated in granules or flexible spheroids. 5 The granules may be coated with a material intended either to allow the modified or prolonged release of the active ingredient(s) embedded in the center of the granules, or to mask the taste of said active 10 ingredient(s), or to avoid solubilizing the active ingredient(s) in the liquid phase of the suspension. The granules and spheroids have a final size of between 50 and 1 000 microns, preferably between 200 and 600 15 microns. They consist of an inert core having a size substantially between 100 and 350 microns and a spherical shape onto which the active ingredient(s) is (are) applied by means of a binder or by mere absorption if the active ingredients are in solution. 20 The granules are for example obtained by coating the active ingredient(s) onto a neutral support consisting of sugar and starch. 25 The coating may be carried out according to several techniques, such as dusting, spraying of a solution, the MELT technique, or any other conventional technology known to persons skilled in the art. 30 The neutral support coated with active ingredient is then optionally coated with a polymer film consisting of a single polymer or of a combination of several polymers or a succession of different layers of polymer, depending on the expected effect. 35 This step may be carried out using the various excipients and technologies well known to persons skilled in the art. Aqueous solvents or the MELT technique will preferably be used.

Flexible spheroids are the subject of as yet unpublished applications FR 97 146 31 and FR 97 146 35, whose content is included by reference in the present 5 application. These spheroids consist of a core and/or of a layer coating said core containing at least one thermoplastic excipient, coated with a deformable flexible film based 10 on a polymeric material whose glass transition temperature is less than 30 0 C. The thermoplastic excipient has a melting point of between 25 and 100 0 C; it is characterized by a pasty to 15 semisolid consistency, at 200C. It may be chosen, inter alia, from partially hydrogenated oils, beeswax and silicone waxes. The polymeric material is preferably an acrylic, vinyl 20 or cellulosic copolymer, to which a plasticizer is optionally added so that its percentage extension is greater than 50%. The oral pharmaceutical suspension according to the 25 invention advantageously consists of a liquid phase which is aqueous or consists of a mixture of water with a cosolvent, for example an oil, propylene glycol, glycerin or a solution of sorbitol. 30 The active ingredient may be chosen, without limitation, from Ibuprofen, Secnidazole hydrate, Erythromycin and its derivatives, Paracetamol, Tinidazole and Codeine. 35 The oral pharmaceutical suspension according to the invention contains a viscosity agent, a filler and a preservative. The viscosity agent is chosen from pharmaceutically - 5 acceptable viscosity agents, for example xanthan gum, hydroxypropylmethyl cellulose, methyl cellulose, carageenan, carboxymethyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone and carboxyvinyl 5 copolymers. The viscosity agent is advantageously a carboxyvinyl copolymer, such as Carbopol*. This viscosity agent has the advantage of being used in small quantities. 10 The viscosity agent represents 0.1 to 10%, preferably 0.1 to 2.5%, by weight relative to the weight of the suspension. 15 The filler represents 10 to 70%, preferably 30 to 55%, by weight relative to the weight of the suspension. The preservative represents 0.05 to 3%, preferably 0.1 to 1%, by weight relative to the weight of the 20 suspension. The preservative is chosen from methyl hydroxy benzoates, propyl hydroxybenzoates, alkylparabens and sorbic acid. 25 The oral suspension according to the invention may contain, in addition, at least one agent chosen from an alkalinizing or acidifying agent, a flavoring, an antioxidant, a surfactant, a coloring, a stabilizer, a 30 lubricant and a sweetener. The sweetener is chosen, for example, from natural or synthetic sweeteners such as sorbitol, sucrose, xylitol, aspartame, saccharin sodium, sodium cyclamate 35 and mixtures thereof. The flavoring is chosen, for example, from products with mint, strawberry and banana flavor. It represents 0.1 to 3% by weight relative to the weight of the -6 suspension. The coloring is, for example, a titanium dioxide or iron oxide pigment. 5 The lubricant is, for example, talc, aluminum oxide or silica. The surfactant is, for example, chosen from sodium 10 lauryl sulfate, polyethylene copolymers, nonionic polyoxypropylene copolymers and mixtures thereof. The surfactant preferably represents 0.1 to 10% by weight relative to the weight of the suspension. 15 The suspension according to the invention is given to the patient in ready-to-use liquid form or in the form of a reconstitutable powder. 20 The reconstitutable powder is prepared by mixing the active ingredient in the form of crystals, granules or spheroids, and the suspending adjuvant. It may be granulated according to the various conventional granulation techniques well known to persons skilled in 25 the art. The powder is then distributed into unit bottles or sachets. The bottles are sufficiently large to allow the quantity of water necessary for the reconstitution 30 to be added. The following examples illustrate the present invention without limiting the scope thereof. 35 Example 1: Suspension of ibuprofen crystals A batch corresponding to 300 liters of suspension, that is 2 000 bottles of 150 ml, is prepared from the following formula -7 COMPONENTS MANUFACTURING FORMULA Ibuprofen 6.00 kg Sucrose 115.50 kg Noncrystallizable sorbitol at 70% 18.30 kg Carbomers (Carbopol" 971 P) 0.51 kg Parabens (Nipasept* base) 0.35 kg Strawberry flavor 0.35 kg Cochineal Red A coloring 0.010 kg Sodium hydroxide (1N solution) 2.00 kg Purified water 208.30 kg Preparation No. 1 Water (127 kg) is introduced into the 200 1 tank at 5 room temperature and then the Carbopol® 971P is dispersed in small quantities in the water. The mixture is homogenized with a deflocculating turbine for 1 hour at 1 500 rpm and then for 4 hours at 800 rpm. 10 Preparation No. 2 A 400 liter jacketed tank is heated to 800C and water (75 kg) is introduced at 80 0 C. The temperature of the water is maintained between 75 0 C and 80 0 C during the 15 preparation. The three-blade AE 200 mm turbine is mounted on the RAYNERI DIRECT T 80 stirrer. The stirring is started and maintained (200 rpm) throughout the preparation. The preservatives and the 20 flavor are dispersed until they are completely dissolved. The sucrose is added and allowed to dissolve completely (the clarity of the solution is checked), the 70% 25 liquid sorbitol is added and then the container is rinsed with water (6.3 kg). The coloring is added and the stirring is continued until a clear solution is obtained.

- 8 The the jacket is cooled and the temperature of the solution is allowed to return to 35 0 C. In the 400 1 tank, the preparation No. 1 is poured, 5 with stirring (200 rpm), into the preparation No. 2. The mixture is homogenized (300 rpm) for at least 30 minutes. A 1N NaOH solution is prepared. A fraction of the 1N NaOH solution is gradually 10 introduced, with stirring (300 to 500 rpm). The mixture is homogenized for 15 minutes. The ibuprofen is introduced, with stirring (500 rpm), and the mixture is homogenized for 1 hour. While maintaining the stirring, the remainder of the 1N 15 NaOH solution is added and then the pH (5.4) is checked. The pH is adjusted, if necessary, to 5.4 with the remainder of the 1N NaOH solution. The mixture is homogenized for 2 hours (300 rpm). The unit volume is adjusted (150 ml) and the bottles 20 are filled. The stirring is maintained in the 400 liter tank and the buffer tank during the filling of the bottles. Bottles are removed at the beginning, in the middle and at the end of the filling. 25 Results beginning middle end bottle 1 99 103 103.5 bottle 2 98.5 101.2 101.2 The content does not vary significantly during the 30 filling. The suspension remains homogeneous. Tests of stability carried out under accelerated conditions 35 (40 0 C and 75% relative humidity) -9 T 0 T 1 month T 3 months Content (mg/ml) 19.0 20.4 19.6 % released (mg/5 ml) 0.35 0.25 0.24 Parabens (mg/ml) 1.17 1.15 1.09 Example 2: Suspension of ibuprofen crystals A batch corresponding to 10 000 bottles of 200 ml is 5 prepared in the example below: COMPONENTS Ibuprofen crystals 40.0 kg Sucrose 770.666 kg Noncrystallizable sorbitol at 70% 122 kg Carbopol" 971 P 3.446 kg Nipagin@ 1.707 kg Nipasol* 0.253 kg Ethyl hydroxybenzoate 0.373 kg Strawberry flavor 2.333 kg Cochineal Red A coloring 0.067 kg Sodium hydroxide 0.533 kg Purified water 1355 kg Preparation The ibuprofen suspension according the same procedure, 10 adapting the material to the size of the batch. A 2 000 liter tank equipped with a jacket is used for the preparation, as well as a 500 liter tank for the preparation of the Carbomer dispersion. 15 Results Samples (1 to 12) are collected during the emptying of the 2 000 liter tank. 2 batches of suspension are prepared and the contents are the following: 20 1 2 3 4 5 6 7 9 10 12 58900 104 107.0 107.3 106 103.3 106 107.7 58901 106.5 106.9 105.2 102.9 108.3 104.8 109.7 101.3 97.9 - 10 The contents are homogeneous, contained in the specifications. 5 Example 3: Suspension of ibuprofen crystals The procedure is carried out as in example 1 The suspension is prepared according to the following formula: Component Unit formula % (w/w) 150 ml* Ibuprofen 3.000 g 1.71 % Sucrose 57.800 g 32.93 % Noncrystallizable sorbitol at 70% 9.150 g 5.21 % Carbomers (Carbopol* 971 P) 0.260 g 0.15 % Parabens (Nipasept@ base) 0.175 g 0.10 % Strawberry flavor 0.175 g 0.10 % Cochineal Red A coloring 0.005 g 0.003 % Sodium hydroxide 0.040 0.02 % Purified water 104.895 g 59.78 % 10 The total parabens representing 0.1% (w/w) of the suspension are a mixture of three para-hydroxybenzoate esters in the following proportions: 73% Methylparaben 15 . 16% Ethylparaben 11% Propylparaben This suspension is subjected to accelerated storage conditions (40 0 C and 75% relative humidity). 20 The results obtained are summarized in the following table. T 0 T 6 months Content mg/g 16.8 20.1 % released mg/g 0.51 0.21 - 11 T 6 months Total microorganisms: (CFU/ml) <1 Yeasts molds CFU/ml <1 Escherichia coli: (CFU/ml) Absence The suspension is stable for six months under these conditions. 5 Tests of the efficacy of the preservatives A microbiological test is carried out according to the method described in the European Pharmacopeia 3rd ed. 10 The test for the suspension of crystals is carried out against a placebo suspension of the same composition but containing no preservative. e suspension with preservatives 15 Inoculum T 0 14 d 28 d CFU CFU RF CFU RF CFU RF Pseudo aeruginosa 3.30x10 6 <100 <10 <10 Staph. Aureus 1.26x10 7 1.85x10 4 <10 <10 E. coli 7.90x10 6 <100 <10 <10 Candida albicans 1.00x10 6 4.85x10 3 <10 <10 Aspergillus nigers 4.65x10 6 5.45x10 5 7.10x10 3 2.8 4.65x10 3 3.0 Ph Eur. 3rd ed. Bacteria Molds Yeasts Conclusion complies complies complies complies - 12 e suspension without preservative Inoculum T 0 14 d 28 d CFU CFU RF CFU RF CFU RF Pseudo aeruginosa 3.30x10 5 3.85x10 5 <10 <10 Staph. Aureus 1.26x10 7 1.22x10 6 <10 <10 Candida albicans 1.00x10 6 1.02x10 5 1.00x10 3 3 4.10x10 4 1.4 Aspergillus nigers 4.65x10 6 5.10x10 5 3.40x10 4 2.1 6.60x10 3 2.8 Ph Eur. 3rd ed. Bacteria Molds Yeasts Conclusion complies complies does not does not comply comply 5 The test meets the criteria of the European Pharmacopeia 3rd ed. The total paraben concentration of 0.1% (w/) allows effective protection of the suspension. 10 Example 4: Suspension of ibuprof en granules containing 20 mg/ml of ibuprofen Formula of the microgranules: Excipients Quantities % (w/w) (g) Ibuprofen 1.19 9.2 Neutres 4.64 35.7 Eudragit E 100® 0.071 0.55 Eudragit NE30D® 0.060 0.46 Colloidal silica 0.006 0.04 Talc 0.024 0.18 Alcohol 95% (solvent) 0.52 15 The microgranules are prepared by spraying successive - 13 layers of active agents followed by a dispersion of coating which makes it possible to mask the bitterness of the active ingredient. 5 Syrup formula: Components % (w/w) Carbopol* 971 P 0.14 Purified water q.s. 100% Ibuprofen granules 1.7 NaOH (1N) q.s. pH = 5.5 Sorbitol at 70% 3.4 Crystal sucrose 30.8 Nipasept® 0.1 Strawberry flavor 0.1 [lacuna] 3 The ibuprofen granules having a titer of 200 mg/g are added in order to obtain a suspension at 20 mg/ml of 10 ibuprofen. The syrup is prepared according to the preceding examples. Example 5: Dry suspension of microgranules 15 The microgranules are prepared as in example 4 2) Formula of the dry adjuvant mixture: Excipients Quantities % (w/w) (g) Carbopol* 971P 46.0 2.62 Sucrose 1529 87.14 Sorbitol 153.0 8.72 Trisodium citrate 10.0 0.57 Cochineal Red 0.6 0.03 Strawberry flavor 11.0 0.63 Total parabens 5.0 0.29 Total dry mass 1745.6 100%

H

2 0 (wetting liquid) 120.0 - 14 The various dry components are mixed for 15 minutes in a cubic mixer. The excipients are then granulated by adding purified water to the mixture, for a sufficient period. The 5 granules are dried at 350C for 3 hours, and then sized on a screen with a 1.25 mm mesh. Final preparation: ibuprofen suspension: Microgranules (g) 6 Dry adjuvant mixture (g) 7 Quantity of water to be added (ml) QS 60 ml Ibuprofen per bottle of 60 ml 1.2 g 10 A quantity of sparklets and of granules is added in the proportion defined in the table above. The suspension is prepared by adding water to the 15 bottle. On stirring vigorously, the granules are dispersed in the liquid phase. After standing for 1 to 2 minutes, the suspension is again stirred. The granules are then homogeneously distributed in the liquid phase and 20 remain in suspension. Example 6: Suspension of ibuprofen microgranules COMPONENTS UNIT FORMULA 150 ml bottles gram % Ibuprofen microgranules 15 8.5 Carbopol® 971 P 0.2 0.11 Sucrose 59.2 33.75 Sorbitol 6.6 3.75 Total parabens 0.06 0.1 Strawberry flavor 0.2 0.1 Coloring <0.01 <0.01 NaOHlM qs pH 5.5 qs pH 5.5 Purified water qs qs - 15 Tests of stability carried out under accelerated conditions (400C and 75% relative humidity) 5 T 0 T 1 month T 3 months Content (mg/5 ml) 103.3 98.1 108.2 % released (mg/5 ml) 0.52 0.63 0.70 T 0 T 1 month T 3 months Total microorganisms <1 <1 <1 Yeasts molds <1 <1 <1 Escherichia coli Absence ND Absence Example 7: Suspension of secnidazole microgranules 10 1) Formula of the microgranules: Excipients Quantities Percentage by mass (g) (%) Secnidazole hydrate 3 20.99 Neutres 2.751 19.25 PVP K30* 0.215 1.50 PEG 4000 0.041 0.29 Eudragit NE30D@ 0.258 1.81 Talc 0.062 0.43 Silica 0.018 0.12 Paraffin 0.634 4.43 Talc 0.317 2.22 Alcohol 95% (solvent) 3.019 Mass of microgranules 7.295 The microgranules are prepared as in example 1.

- 16 2) Formula of the adjuvant mixture: Carbopol 971 P® 0.184 1.28 Icing sugar 6.1 42.67 Neosorb PlOOT® 0.61 4.27 Trisodium citrate 0.034 0.28 Cochineal Red 0.002 0.02 Strawberry flavor 0.044 0.31 Nipasept® 0.02 0.14

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2 0 (wetting liquid) 0.48 Mass of microgranules 7.000 Total dry mass 14.295 100% Final preparation: secnidazole suspension 5 Mass of microgranules (g) 7 Mass of the adjuvant mixture (g) 14.295 Quantity of water to be added (ml) QS 60 ml Mass of Secnidazole per bottle of 60 ml 1.5 g Example 8: Suspension of erythromycin microgranules 1) Formula of the microgranules: 10 Excipients Quantities Percentage by mass (g) (%) Erythromycin 1.500 11.48 Neutres 3.200 24.49 PVP K30@ 0.058 0.44 Fine crystal sucrose 0.187 1.44 Eudragit L30D& 0.300 2.30 Triethyl citrate 0.030 4.04 Gelucire® 0.528 2.02 Talc 0.264 Solvent QS Mass of microgranules 6.067 The microgranules are prepared as in example 1.

- 17 2) Formula of the adjuvant mixture: Carbopol 971 P* 0.184 1.40 Icing sugar 6.100 46.68 Neosorb PlOOT@ 0.610 4.67 Trisodium citrate 0.04 0.31 Cochineal Red 0.002 0.02 Strawberry flavor 0.044 0.34 Nipasept 0.02 0.15

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2 0 (wetting liquid) 0.48 Mass of microgranules 7.000 Total dry mass 13.067 100% Example 9: Suspension of erythromycin microgranules 5 1) Formula of the microgranules Raw materials Formula in % Neutres 23.77 Erythromycin 23.55 Coating by dusting Eudragit L30D@ 2.16 Triethyl citrate 0.22 Eudragit L30D@ 4.97 Triethyl citrate 0.50 1st protective coating Talc 0.75 Precirol® 2.24 2nd hydrophobic coating Talc 1.12 Eudragit L30D* 32.59 Triethyl citrate 3.26 3rd protective coating Talc 4.89 - 18 2) Formula of the suspension containing a dose of 125 mg/5 ml Raw materials Formula in % Erythromycin microgranules 10. 5 Avicel RC 591* 3.4 Purified water (qs) 52.6 Sucrose at 60% 26.2 Liquid sorbitol at 70% 5.6 Nipasept* 0.1 Strawberry flavor 0.1 Citric acid 0.1 Thick glycerin 1.4 5 Example 10: Suspension of Tinidazole microgranules 1) Formula of the tinidazole granules Raw materials Formula in % Neutres 6.02 Tinidazole 40.14 Coating PVP K 30@ 3.21 Triethyl citrate 0.32 Eudragit L30D® 4.97 Triethyl citrate 0.50 Protective coating Talc 0.75 Precirol 2.24 Hydrophobic coating Talc 1.12 Eudragit L30D® 32.59 Triethyl citrate 3.26 Coating Talc 4.89 - 19 2) Formula of the suspension containing a dose of 50 mg/ml Raw materials Formula in % Tinidazole microgranules 10.68 Carbomer 971 P® 0.13 Crystal sucrose 29.99 Liquid sorbitol at 70% 4.73 Nipasept* 0.10 Strawberry flavor 0.10 Sodium hydroxide (pellets) 0.45 Purified water 53.82

Claims

1. An oral pharmaceutical suspension consisting of a liquid phase in which one or more solid active 5 ingredients are dispersed, characterized in that the soluble fraction of said active ingredient(s) in the liquid phase is less than 10% by weight relative to the weight of the suspension. 10

2. The oral pharmaceutical suspension as claimed in claim 1, characterized in that the soluble fraction is less than 5% by weight, preferably 1% by weight relative to the weight of the suspension. 15

3. The oral pharmaceutical suspension as claimed in claim 1 or 2, characterized in that the active ingredient(s) is (are) in the form of crystals or formulated in granules or flexible spheroids. 20

4. The oral pharmaceutical suspension as claimed in claim 3, characterized in that the granules are coated with a material intended to mask the taste of the active ingredient(s) or to allow the 25 modified or prolonged release of the active ingredient(s).

5. The oral pharmaceutical suspension as claimed in claim 3, characterized in that the size of the 30 crystals is less than 500 microns.

6. The oral pharmaceutical suspension as claimed in claim 3, characterized in that the size of the granules or of the spheroids is between 50 and 35 1 000 microns.

7. The oral pharmaceutical suspension as claimed in one of the preceding claims, characterized in that - 21 the liquid phase is aqueous or consists of a mixture of water and of a cosolvent, such as an oil, propylene glycol, glycerin or a solution of sorbitol. 5

8. The oral pharmaceutical suspension as claimed in one of the preceding claims, characterized in that the active ingredient is chosen from Ibuprofen, Secnidazole Hydrate, Erythromycin and its 10 derivatives, Paracetamol, Tinidazole and Codeine.

9. The oral pharmaceutical suspension as claimed in one of the preceding claims, characterized in that it contains a viscosity agent, a filler and a 15 preservative.

10. The oral pharmaceutical suspension as claimed in claim 9, characterized in that the viscosity agent is chosen from xanthan gum, hydroxypropylmethyl 20 cellulose, methyl cellulose, carageenan, carboxymethyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone and carboxyvinyl copolymers. 25

11. The oral pharmaceutical suspension as claimed in claim 9 or 10, characterized in that the viscosity agent represents 0.1 to 10%, preferably 0.1 to 2.5%, by weight relative to the weight of the suspension. 30

12. The oral pharmaceutical suspension as claimed in one of claims 9 to 11, characterized in that the filler represents 10 to 70%, preferably 30 to 55%, by weight relative to the weight of the 35 suspension.

13. The oral pharmaceutical suspension as claimed in one of claims 9 to 12, characterized in that the preservative represents 0.05 to 3%, preferably 0.1 - 22 to 1%, by weight relative to the weight of the suspension.

14. The oral pharmaceutical suspension as claimed in 5 one of claims 9 to 13, characterized in that the preservative is chosen from methyl hydroxy benzoates, propyl hydroxybenzoates, alkylparabens and sorbic acid. 10

15. The oral pharmaceutical suspension as claimed in one of claims 9 to 14, characterized in that it comprises, in addition, at least one agent chosen from an alkalinizing or acidifying agent, a flavoring, an antioxidant, a surfactant, a 15 coloring, a stabilizer, a lubricant and a sweetener, the sweetener being chosen from natural or synthetic sweeteners such as sorbitol, sucrose, xylitol, aspartame, saccharin sodium, sodium 20 cyclamate and mixtures thereof, the flavoring representing 0.1 to 3% by weight relative to the weight of the suspension, the coloring being a titanium dioxide or iron oxide pigment, 25 the surfactant being chosen from sodium lauryl sulfate, polyethylene copolymers, nonionic polyoxypropylene copolymers and mixtures thereof, and the surfactant representing 0.1 to 10% by weight relative to the weight of the suspension.