WO2013024373A1

WO2013024373A1 - Pharmaceutical composition comprising cefuroxime

Info

Publication number: WO2013024373A1
Application number: PCT/IB2012/053283
Authority: WO
Inventors: Manish Dhanuka; Vishal Ashoka DHOKA; Ravi Pratap SRIVASTAVA; Ashoka DHOKA
Original assignee: Dhanuka Laboratories Ltd.
Priority date: 2011-08-12
Filing date: 2012-06-28
Publication date: 2013-02-21
Also published as: EP2741750A1

Abstract

The present invention discloses a composition of taste masked oral suspension which comprises of bitter taste Cefuroxime axetil, having integral coating of lipid and sweetener system. The sweetener system which is used in composition is disclosed in the invention. The said composition delivers substantial amount of drug immediately at the gastric p H with improved palatability.

Description

PHARMACEUTICAL COMPOSITION COMPRISING CEFUROXIME

Field of the invention

This present invention provides an oral composition containing of cefuroxime axetil for improving the dissolution and palatability by taste masking the bitter taste of drug. Most importantly the present invention relates to bitterness inhibition of drug by dispersing the active drug in molten lipid matrix and then blending the granules with sweetener system to improve the palatability.

Background of the invention

Variety of delivery system are being developed for different routes of administration like oral, parental , nasal and transdermal, the oral route being the most attractive for drug delivery, as this mode of administration is an easy , conventional , noninvasive and familiar method of drug delivery. The common oral dosage form include , liquid mixture like solution, suspension, solid dosage form like tablets , capsules and liquid filled capsules etc. However patient at extremes of ages , such as children and the elderly , often experience difficulty in swallowing solid oral dosage form, for these patients the drug are mostly in liquid dosage form such as solution , suspension and emulsion. This dosage form usually lead to perceptible exposure of active ingredients to taste buds and if the active ingredient is bitter this gives extremely unpleasant bitter taste.

Hence taste is important parameter governing the compliance. Taste masking is major problem when the drug is extremely unpleasant and bitter in taste. This problem is not restricted to liquid oral composition like solution and syrups but is also encountered in oral dry suspension wherein the dosage form usually lead to perceptible exposure of active ingredients to taste buds.

Cefuroxime, as disclosed in British Patent Specification No. 1453049, is a valuable broad spectrum antibiotic characterized by high activity against a wide range of gram - positive and gram - negative micro - organism , this property being enhanced by the very high stability of the compound to β lactamase produced by a range of gram negative micro - organism. Cefuroxime and its salts are principally of value as injectable antibiotic since they are poorly absorbed from the gastro - intestinal tract.

A convenient means of presenting antibiotic for oral administration is in the form of granules which may be administered as a solution or suspension. Solution or suspension of granules as, for example, syrup is particularly convenient for oral administration of antibiotics to children. However, Cefuroxime axetil has an extremely bitter taste which is long lasting and unpleasant.

Another problem arises from the Cefuroxime axetil, both in crystalline form and the amorphous form is to form a gelatinous mass when contacted with aqueous media. This gelling effect is temperature dependent but does occur at temperatures of about 37°C that is at the physiological temperatures at which disintegration of an orally administered granule would take place. Where there is relatively slow dispersion of Cefuroxime axetil into the surrounding aqueous medium following ingestion there is still the risk that the Cefuroxime axetil present in the composition may gel. Such gel formation may lead to poor dissolution of the Cefuroxime axetil and hence poor absorption from the gastrointestinal tract that is low bioavailability. In the case of granule formulation the use of particles of a small diameter and high surface area is desirable to avoid such gelling.

In the formulation of Cefuroxime axetil into granules it is important to avoid the release of the drug into any liquid medium in which it is suspended or indeed into the mouth when administering. Such problem may be minimized by formulating the Cefuroxime axetil as lipid coated particles.

GB 2204792 discloses a particulate formulation in which the above problem is addressed. This patent disclose a composition comprising Cefuroxime axetil in particulate form , the particles being provided with integral coating of lipid or a mixture of lipids which are insoluble in water and which are serve to mask bitter taste of Cefuroxime axetil upon oral administration but which disperse or dissolve on contact with gastrointestinal fluid.

WO 94/25006 disclose a method of masking the flavour of bitter tasting drugs in particulates form by mixing the drug with a lipid at a temperature below that where significant drug degradation occurs.

US Patent No 7378109 discloses composition comprising a Lipid - polymer matrix to mask the bitter or unpleasant taste of the medicament. The lipid or blend of lipids, are used in combination with pH dependent polymer where the said polymer is acid soluble or swell able and mixed with flavouring agent sucrose, aspartame and saccharin. WO 2005/094791 Patent discloses the invention relating to the process of coating of cefuroxime axetil with lipid or mixture of lipids to mask the bitter taste of cefuroxime axetil .The process comprises the step of atomizing the molten lipid or mixture of lipids on air- mixing particulate cefuroxime axetil, solidification of the molten lipid or mixture of lipid on particulate cefuroxime axetil and recovering said lipid or mixture of lipids coated cefuroxime axetil particles.

However lipid coating does some extent to mask the bitter taste of cefuroxime axetil upon oral administration, but cefuroxime axetil is so bitter that its suspension composition still leave a bitter taste which is unpleasant in taste when administered to children, this factor may affect the patient compliance, and less palatable antibiotic are likely to be discontinued as soon as the patient is well rather than continuing the course for the prescribed duration.

This problem is overcome in the WO 2003/043638 application which reveals a composition comprising of cefuroxime axetil coated with integral coating of lipid and mixture of lipids which are in soluble in water, this composition further comprises of sweetener system and a texture modifier which serve to mask the bitter taste of cefuroxime axetil upon oral administration.

The above Applicant currently markets a same patented oral suspension composition comprising Cefuroxime axetil, the particle being provided with integral coating of a lipid in the U K under the trade name Zinnat™ and in the US under Trade name Ceftin™. This oral suspension comprises in addition to Cefuroxime axetil, the inactive ingredients stearic acid, tutti frutti flavor, a binding agent (povidone K 30) .

WO 2007/061803 Patent relates to functional sweeteners composition comprising non - caloric or low - caloric natural or synthetic, high potency sweeteners and method of masking and using them. This invention discloses in its specification the use of different functional sweetener comprising of atleast one non - caloric or low caloric natural or synthetic, high potency sweetener, at least one sweet taste improving sweetener, and atleast one functional ingredient, such as C - reactive protein reducing substance. This invention also includes the method to improve the taste of non - caloric or low caloric high potency sweetener by imparting a more sugar like taste or characteristic.

The marketed taste masked formulation compries of a texture modifier as one of the ingredients which contributes to an enhanced taste masking effect. However , the present invention provides a taste masking composition of Cefuroxime axetil for oral administration comprising sweetener system in the absence of a texture modifier which surprisingly provides a better mouth feel with an improvement in terms of less grittiness.

Object of the invention :

An object of the invention is to provide an efficient taste masking composition of cefuroxime axetil.

Another object of the invention is to provide a process for the preparation of the said composition.

Yet another object of the invention is to provide a taste masking composition of cefuroxime axetil which is devoid of texture modifier.

Still another object of the invention is to provide a taste masking composition for oral administration.

Still yet another object of the invention is to provide a composition which is either in granular form or suspension form.

Summary of the Invention:

The present invention describes a composition comprising Cefuroxime axetil in particulate form, the particle being provided with integral coating of lipid which is insoluble in water and which disperse or dissolve on contact with gastrointestinal fluid. The composition further comprises of sweetener system in an amount sufficient to mask the bitter taste of Cefuroxime axetil, bulk sweetener and a binding agent. More particularly, the present invention provides a composition comprising Cefuroxime axetil in particulate form the particle being provided with integral coating of lipid which is insoluble in water and importantly a "sweetener system" comprising of atleast three sweetners selected from aspartame, neotame, acesulfame potassium, xylitol, sorbitol ,mannitol and sucralose to mask the bitter taste of Cefuroxime axetil.

Advantageously, it has been found that the sweetener system used in the composition of present invention prove to be better to overcome the bitter taste, which has been evaluated and results discussed herein below in this application.

Detail Description Of The Invention

The inventive oral suspension comprising coated cefuroxime amorphous drug has the features of masking the drug bitterness by lipid coating and drug bitterness is furthered inhibited by the use of sweetener combination.

The taste masked composition of present invention comprises a bitter tasting active drug, wherein the active drug used is cefuroxime axetil , a integral coating of lipid which is insoluble in aqueous media and serve to mask the bitter taste of cefuroxime axetil upon oral administration , a "sweetener system" as lipid coating goes up to some extend to provide bitterness inhibition.

The composition of cefuroxime axetil may contain cefuroxime axetil in crystalline form but more preferably in amorphous form, for example as described in British patent specification No. 2127401.

Suitable lipid includes fatty acid or monohydric alcohols thereof, fixed oils, fats, waxes, sterols, phospholipids and glycolipids. The lipid may, for example, be a high molecular weight straight chain saturated or unsaturated aliphatic acid, such as stearic acid or palmitic acid; a triglyceride for example a glyceryl ester of high molecular weight aliphatic acid, such as glyceryl trilaurate or glyceryl trimyristate; a wax for example beeswax or carnauba wax; a high molecular weight straight chain aliphatic alcohol such as stearyl alcohol or cetyl alcohol or a mixture thereof.

A particularly preferred lipid providing good bioavailability and having physical property particularly compatible with cefuroxime axetil is stearic acid.

The lipid coated particles according to the invention will preferably contain from 5 to 100%, more preferably 5 to 90%, more preferably 5 to 75% by weight of cefuroxime axetil.

The present invention comprises a binding agent from one of the known binding agents conventionally used in the field of pharmaceutical industries, which include synthetic polymers such as copovidone (e.g kolidon VA64, BASF) hydroxpropylmethylcellulose, polyvinylpyrrolidone (e.g Kolidon K 30) and hydroxypropylmethylcellulose , natural gums such as Arabic gum and xanthan gum , and a mixture thereof. A particularly preferred binder used in the composition is polyvinylpyrrolidone (PVP K30).

The amount of binding agent may be 0.1 to 0.5% by weight, preferably 0.1 to 1 % based on the total weight of the inventive oral suspension.

The present oral suspension comprises of "sweetener system" which means a sweetener or combination of sweeteners which are added to the bulk sweetener during the granulation process to form a acceptable level of sweetness for the preparation .The sweetener system are used either in combination of two or admixture of third sweetener.The sweetener system comprises of sweetners selected from a group of natural and artificial sweeteners.

The artificial sweeteners and natural sweetener is selected from a group of sweetners consisting of aspartame, acesulfame potassium, sucrose, sucralose, mannitol, xylitol, sorbitol.

The sweetener system comprises of mixture of sweeteners selected from neotame, acesulfame potassium, aspartame which is about 0.01 - 10 % by weight of the final granule composition.

The sweetner system of the present invention contains at least three sweetners of which one sweetner is a polyol, preferably sugar alcohol.

Suitable bulk sweetener include sucrose, starch, lactose, fructose and glucose.

Sucrose is used as suitable bulk sweetener in the ratio of 5 - 60%, more preferably 5 - 80%> and more preferably 5 - 90% by weight of final pharmaceutical composition.

Suitable flavouring such as mint, peppermint, strawberry or tutti frutti may additionally be present in the composition.

Peppermint flavour is used in the final composition as the flavouring agent in the ratio 0.01 - 0.1% by weight of final pharmaceutical composition.

In a preferred embodiment, cefuroxime axetil are granulated aqueous solution of polyvinylpyrrolidone (povidone) as a binder to form granules than lipid coating is done to obtain coated granules of cefuroxime axetil. A suitable flavor, such as Peppermint flavour, is added and the composition is blended, after or at the same time as addition of flavouring agent to form the final granule composition. Alternatively, the sweetener and flavour may be blended with lipid coated particles after the granulation process.

The Pharmaceutical Composition of the invention, formulated for oral administration as a suspension, may be constituted with a suitable amount of water, for use in oral administration of cefuroxime axetil. Particles will typically present so as to give a multidose suspension containing the equivalent of 125 mg/5 ml cefuroxime axetil or 250 mg/5 ml dose of cefuroxime axetil.

The present invention may further illustrated by the following example which should not be construed as constituting a limitation thereto. Examples

The cefuroxime axetil used in the examples was highly pure spray dried amorphous material. The Sweetener system was blended together with the cefuroxime axetil granules as a dry mix ensuring that they are evenly in admixture.

Example 1

In the Sweetener system comprises of acesulfame potassium & neotame were blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1 Cefuroxime Axetil 30.08 6.68

2 Stearic Acid 14.53 3.23

3 PVPK 30 3.05 0.68

4 Acesulfame Potassium 52.66 11.70

5 Neotame 1.34 0.30

6 Flavour Peppermint 0.38 0.08

7 Sucrose 347.96 76.32

8. Total 450 100 Example 2

In the Sweetener system comprises of neotame & aspartame were blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

Example 3

In the Sweetener system comprises of neotame & acesulfame along with the third sweetener aspartame was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1. Cefuroxime Axetil 15.04 3.30

2. Stearic Acid 7.38 1.64 3. PVPK 30 1.55 0.34

4. Acesulfame Potassium 4.86 1.1

5. Neotame 0.92 0.21

6. Aspartame 21.85 4.85

7. Flavour Peppermint 0.19 0.04

8. Sucrose 398.18 88.48

9. Total 450 100

Cefuroxime Axetil oral suspension 250mg/5ml

Example 4

In the Sweetener system comprises of acesulfame, neotame along with the third sweetener sucralose was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture

Cefuroxime Axetil oral suspension 125mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1 Cefuroxime Axetil 15.04 3.30

2 Stearic Acid 7.38 1.64

3 PVPK 30 1.55 0.34

4 Acesulfame Potassium 4.86 1.1

5 Neotame 0.92 0.21

6 Sucralose 21.85 4.85

7 Flavour Peppermint 0.19 0.04

8 Sucrose 398.18 88.48

9. Total 450 100 Cefuroxime Axetil oral suspension 250mg/5ml

Example 5

In the Sweetener system comprises of acesulfame, neotame & along with sugar alcohol mannitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1. Cefuroxime Axetil 30.08 6.68

2. Stearic Acid 14.53 3.23

3. PVPK 30 3.05 0.68

4. Acesulfame Potassium 9.60 2.13

5. Neotame 1.84 0.41 6. Mannitol 42.56 9.46

7. Flavour Peppermint 0.38 0.08

8. Sucrose 347.96 77.32

9. Total 450 100

Example 6

In the Sweetener system comprises of acesulfame, neotame along with sugar alcohol xylitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1. Cefuroxime Axetil 30.08 6.68

2. Stearic Acid 14.53 3.23

3. PVPK 30 3.05 0.68

4. Acesulfame Potassium 9.60 2.13

5. Neotame 1.84 0.41

6. Xylitol 42.56 9.46

7. Flavour Peppermint 0.38 0.08

8. Sucrose 347.96 77.32

9. Total 450 100 Example 7

In the Sweetener system comprises of acesulfame, neotame along with sugar alcohol sorbitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

Example 8

In the Sweetener system comprises of acesulfame, neotame & along with the third sweetener sucralose was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture. Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

Example 9

In the Sweetener system comprises of neotame, sucralose along with sugar alcohol mannitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1 Cefuroxime Axetil 15.04 3.30

2 Stearic Acid 7.38 1.64

3 PVPK 30 1.55 0.34

4 Sucralose 4.86 1.1

5 Neotame 0.92 0.21 6 Mannitol 21.85 4.85

7 Flavour Peppermint 0.19 0.04

8 Sucrose 398.18 88.48

9. Total 450 100

Cefuroxime Axetil oral suspension 250mg/5ml

Example 10

In the Sweetener system comprises of neotame, along with sugar alcohol xylitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1 Cefuroxime Axetil 15.04 3.30

2 Stearic Acid 7.38 1.64

3 PVPK 30 1.55 0.34

4 Sucralose 4.86 1.1

5 Neotame 0.92 0.21

6 Xylitol 21.85 4.85

7 Flavour Peppermint 0.19 0.04

8 Sucrose 398.18 88.48

9. Total 450 100 Cefuroxime Axetil oral suspension 250mg/5ml

Example 11

In the Sweetener system comprises of neotame, sucralose along with sugar alcohol sorbitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1. Cefuroxime Axetil 30.08 6.68

2. Stearic Acid 14.53 3.23

3. PVPK 30 3.05 0.68

4. Sucralose 9.60 2.13 5. Neotame 1.84 0.41

6. Sorbitol 42.56 9.46

7. Flavour Peppermint 0.38 0.08

8. Sucrose 347.96 77.32

9. Total 450 100

Example 12

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

S. No. Name of the Items (API & Excipient) Qty in Kg %w/w

1. Cefuroxime Axetil 30.08 6.68

2. Stearic Acid 14.53 3.23

3. PVPK 30 3.05 0.68

4. Sucralose 9.60 2.13

5. Acesulfame potassium 1.84 0.41

6. Sorbitol 42.56 9.46

7. Flavour Peppermint 0.38 0.08

8. Sucrose 347.96 77.32

9. Total 450 100 Example 13

In the Sweetener system comprises of neotame, sucralose along with sugar alcohol xylitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture.

Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

Example 14

In the Sweetener system comprises of neotame, sucralose along with sugar alcohol mannitol as sweetener was blended together with the cefuroxime axetil lipid coated granules as a dry mix ensuring that they are evenly in admixture. Cefuroxime Axetil oral suspension 125mg/5ml

Cefuroxime Axetil oral suspension 250mg/5ml

Example 15

This is a patented oral suspension composition comprising Cefuroxime axetil, in U K under the trade name Zinnat™ and in the US under Trade name Ceftin™. This oral suspension comprises in addition to Cefuroxime axetil, stearic acid, tutti frutti flavor, a binding agent (povidone K 30) and sucrose as a bulk sweetener.

Cefuroxime Axetil oral suspension 125mg/5ml (Zinnat™)

S. No. Ingredients Qty in Kg %w/w

1. Cefuroxime axetil 15.00 3.55

2. Stearic acid 85.20 20.19

3. Povidone 1.30 0.31

4. Tutti Frutti flavour 10.00 2.37 5. Sucrose 306.20 72.56

6. Acesulfame Potassium 2.10 0.50

7. Aspartame 2.10 0.50

8. Xanthum gum 0.10 0.02

9. Total 422 100

Results :

A taste trial was performed in which ten volunteers assessed a suspension of composition of example 1 reconstituted with portable water according to the following categories.

Initial taste : Sweet or bitter

Aftertaste : bitter aftertaste present or absent

Mouth feel : creamy or gritty

Flavour : pleasant or unpleasant

The results of the taste trials are tabulated below:

After reconstitution of suspension with portable water taste trial was performed between "two sweetener system:, "three sweetener system" & "marketed suspension" Formulations in three example were assessed in the "fresh" form, i.e freshly constituted formulation.

In a preference test design, the suspension were compared for sweetness, bitterness, mouth feel and overall preference. The result demonstrated in the following tables show percentage of patient preference for both a 125/5ml dose form and 250mg/5ml dose form. Suspension Sweeter Bitter Better Mouth Preference

feel

125mg/5ml trials

Suspension l^a 95% 0% 95% 50%

Suspension 2^b 60% 30% 60% 10%

Suspension 3° 85% 0% 85% 40%

250 mg/5ml trials

Suspension l^a 95% 0% 95% 60%

Suspension 2 60% 30% 60% 0%

Suspension 3° 85% 0% 85% 40%

Suspension 1 : cefuroxime axetil lipid coated particles plus a "sweetener system" comprising three sweetener.

bSuspension 2: Cefuroxime axetil lipid coated particles plus "sweetener system" comprising two sweetner.

cSuspension 3: Market preparation of cefuroxime axetil oral suspension (Brand name : Zinnat)

After observing that the sweetener system comprising of three sweetener was found to be better than sweetener system containing two sweeteners for mouth feel. Finally, the taste masking composition of cefuroxime axetil comprising of three sweeteners was evaluated for mouth feel against marketed product Zinnat (example 15) . Surprisingly, the compositions of example 9, 10 & 11 was found to be better than the marketed product. The results have been presented in the table here in above.

Claims

Claims:

1. A composition comprising cefuroxime axetil in particulate form, the particles being provided with integral coating of lipid which is insoluble in water, which disperse or dissolve on contact with gastrointestinal fluid, a bulk sweetener, a binding agent and a sweetener system comprising at least three sweetners in amounts sufficient to mask the bitter taste of cefuroxime axetil.

2. A composition according to claim 1, wherein one of the sweetners of the sweetner system is a polyol, preferably a sugar alcohol.

3. A composition according to claim 2 wherein the sugar alcohol is selected from group consisting of mannitol, xylitol and sorbitol.

4. A composition according to claim 1 wherein the sweetener system consist of at least three artificial derived sweeteners selected from the group consisting of neotame, acesulfame potassium, sucralose, aspartame , mannitol, xylitol and sorbitol.

5. A composition according to claim 1 wherein the most preferred sweetener system is sucralose , neotame and sugar alcohol and preferably a sweetener system asesulfame potassium, sucralose and sugar alcohol.

6. A composition according to claims 1 wherein the sweetener system comprises of three sweeteners admixture in weight ratio of 1 : 0.1 : 4 to about 1.5:0.5:6

7. A composition according to claims 1 or 2 wherein the sweetener system sucralose, neotame & sugar alcohol is used in the weight ratio of 1 : 0.1 : 4 to about 1.5:0.5:6

8. A composition according to claim 1 wherein the sweetener system Acesulfame Potassium, Neotame and sugar alcohol used in the ratio of 1 : 0.1 : 4 to about 1.5:0.5:6

9. A composition according to claim 1 wherein the binder is selected from group consisting of polyvinypyrrolidone, methycellulose, hydroxyalktlycellulose, such as hydroxymethycellulose , sodium carbovymethyl celulose or misture thereof.

10. A composition in claim 9 according to which the preferable binding agent is Po lyvinylpyrro lidone .

11. A composition according to claim 1 wherein the flavouring agent is selected from group consisting of mint, peppermint, strawberry and Tuttifrutti.

12. A composition of claim 9 according to which the flavouring agent is flavour peppermint

13. A composition according to claim 1 wherein the lipid or lipid mixture used is selected from the group consisting of steaaric acid , palmitic acid; aliphatic acid, glyceryl trilaurate or glyceryl trimyristate , beeswax , carnauba wax, stearyl alcohol and cetyl alcohol .

14. A composition according to claim 13 wherein the preferable lipid is stearic acid in the weight.percentage of 1 - 5% .

15. A process for the preparation of a composition as claimed in claim 1, which comprises dispensing particulate Cefuroxime Axetil in a molten lipid or mixture of lipids providing particles having integral coating of the lipids or lipid mixture, cooling and collecting particles thereby obtained.

16. A process as claimed in claims 1 and 2 wherein the particulates Cefuroxime axetil prior to coating has mean particle diameter by volume in the range of 5 to 50 micron.

17. A process as claimed in claim 15 wherein the amount of particulate cefuroxime axetil and lipid or lipid mixture used are as such to provide coated particles containing cefuroxime axetil in the range 5 to 30% by weight

18. A pharmaceutical composition for oral administration comprising a composition as claimed in claim 1 or as prepared in claim 15 together with one or more pharmaceutical carriers or excipients.

19. A pharmaceutical composition as claimed in claim 18 in the form of granules.

20. A pharmaceutical composition as claimed in claim 18 in the form of an aqueous suspension.

21. A pharmaceutical composition as claimed in claim 18 containing orally acceptable solute serving to assist in maintaining the taste masking properties of the lipid coating.

22. A pharmaceutical composition as claimed in claim 18 wherein the solute is sugar in the concentration range of 80 to 90 %weight percent.

23. A pharmaceutical product as claimed in claim 1, subtaintially as herein described.

24. A process as claimed in claim 15 substantially as herein described.

25. A pharmaceutical composition as claimed in claim 18 substantially as herein described.