The present invention relates to pharmaceutical formulations comprising ready to use cephalosporin suspension. The present invention also describes the process of formulating such formulations. Further, the preferable suspension is formulated without the use of water so as to protect the cephalosporin from accelerated degradation.
PRIOR ART
Cephalosporin antibiotics are a subset of the (3-lactam family of antibiotics and are used to treat bacterial infections.
Cephalosporins are one of the main treatment strategies in various bacterial infections due to their high efficacy and potent action against the most notorious bacteria.
The core structure of cephalosporin antibiotic is shown below
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Cephalosporins disrupt synthesis of the peptidoglycan layer of bacterial cell walls. Peptidoglycan is a strong structural molecule specific to the cells walls of bacteria. With the cell wall structure compromised, the bactericidal result is lysis and death of the cell.
Till now, the convenient means of administering the antibiotic in the form of oral liquid is for oral administration is in the form of granules which may be administered as a solution or suspension or taken with a draught of water. Solutions or suspensions 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 which cannot be adequately masked by the addition of sweeteners and flavours to conventional granule presentations.
Another problem arises from the 'tendency of cefuroxime axetil, both in crystalline form and the amorphous form to form* a gelatinous mass when contacted with aqueous media.
US 5599557 discloses dry hydrated cephalosporin, e.g. ceftibuten having about 7 to 14% by weight of water, powder formulation, pharmaceutical compositions in the form of an oral suspension dosage form and a method of making the dry powder formulations.
5606/CHENP/2014 claims a suspension formulation for administration to an animal, the suspension formulation including: at least one

cephalosporin antibiotic or a pharmaceutical^ similar salt thereof; oil; and a glycerol acetate solvent.
OBJECTIVE OF THE INVENTION
The object of the present invention is to provide a suspension of cephalosporin antibiotic.
Another object of the present invention is to provide a ready-to-use suspension of cephalosporin.
Yet another object of the present invention is to provide a formulation which is stable and the active substances does not deteriorate.
Yet another object of the present invention is to provide a formulation of cephalosporin with a suitably masked bitter taste.
DETAILED DESCRIPTION OF THE INVENTION
The present invention discloses a stable, ready-to-use oral formulation and the method of manufacture for such formulations.
The main disadvantage of this dosage form is that they should be used within 7-14 days of reconstitution and also the water is required for reconstitution. Sometimes the patients failed to understand that the water required should be first boiled and then cooled so as to free it from bacterial contaminations. The patient instead uses the general

water, as water for reconstitution, leading to the risk of increased infection.
Since the drug is unstable in the presence of water, thus the present invention provides the final formulation devoid of water or very less amount of water. The formulation is thus formulated by judicious use of the solvent system as the cephalosporin class of drugs has a bitter taste.
The present invention also avoids the gelling tendency of cephalosporin, particularly cefuroxime so as to provide a formulation which delivers exact amount of dose required.
The technology used in the formulation is a drug-resin complex which helps in increasing the absorption, taste masking and stability of the cephalosporin.
The formulation, according to the present invention, contains the oral suspension of cephalosporin, more particularly cefuroxime and cefpodoxime along with other pharmaceutical excipients which aid in the stability and taste masking of the formulation and make the formulation in ready-to-use form.
The pharmaceutical excipients can be selected from the group comprising Taste Masking agent, Solvent for taste masking, Taste enhancer, suspending agent, Sweetener, Antioxidant, Flavor and Suspension Base.

The taste masking agent can be selected from the group comprising\ Polyacrylic copolymer, Methyacrylic acids, Polysteryene derivatives and Cellulose Derivatives or the combinations thereof.
Chelating agents used, according to the embodiments of the present invention, can be selected from the group comprising Di-Sodium EDTA Edetic acid, Dimercaprol, Diethylene trimine pentacetic acid (DPTA) and Desferrioxamine or the combination thereof.
Surfactants used in the present invention can be selected from the group comprising Polysorbates, Caprylic Glyceride, Poloxamer, Polyoxyl 35 Castor oil and Polyoxyl 40 Castor oil or the mixtures thereof.
Antioxidants used in the formulation of the present invention can be selected from the group comprising Sodium Sulfite, Vitamin E acetate, Ascorbic acid, Butylated Hydroxy Toluene, Butylated Hydroxy Anisole, and Sodium Metabisulphite or the combination thereof.
Solvent used can be selected from the group comprising Acetone, Purified Water, Methylene Chloride and Isopropyl alcohol and combinations thereof.
Vehicles used in the present invention can be selected from Medium Chain Triglycerides and Soyabean oil or the combination thereof.

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Thickening agents used in the present invention can be selected from the group comprising Mannitol, Colloidal silicon dioxide and Lactose or the combination thereof.
The list of excipients mentioned above is the general excipients that can be used but does not, in any manner, limit the scope of the invention. The suitable excipients, other than mentioned above, can also be used and are under the scope of the present invention.
The formulation according to the present invention, can be developed, but not limited to, in the following manner:
FORMULATION OF CEFPODOXIME READY-TO-USE ORAL SUSPENSION

S. No. Material Name Label Claim UOM Quantity Required
1. Cefpodoxime Proxetil 100 mg/ 5 ml Kg 2.000*
2. Kyron T-114 - Kg 6.000
3. Acetone - Ltr. 30.000
4. Purified Water - Ltr.. 70.000
5. Mannitol - Kg 5.000
6. Citric Acid - Kg 0.500
7. Colloidal Silicon Dioxide - Kg 1.000

8. Aspartame - Kg 1.000
9. Sodium Saccharine - Kg 0.250
10. Butylated Hydroxy toluene - Kg 0.010
11. Sodium Chloride - Kg 0.200
12. Flv. Pineapple - Kg 0.100
13. Corn Oil (Medium Chain Triglyceride) - Ltr. 84.00
Procedure:-
1) DRUG RESIN COMPLEX: - Mix the required quantity of acetone and water.
2) Mix the require quantity of Cefpodoxime Proxetil and Kyron T-114 accurately and shift through # sieve 40.
3) Slowly add the above mixture in to step 1st with continuous stirring for 20-30 minutes.
4) Observe the pH below 5.5 and stir this solution for another 2.0 hours.
5) Dry the taste masked complex in dryer at 40°C until LOD below 5% w/w.
6) Pass the dry drug resin complex through #40 sieve.
7) READY MIX SUSPNSION: Take 50 Litre of Corn oil and add 0.01 Kg of Butylated Hydroxy Toluene stir to get dissolve completely.

8) Now take Drug Resin Complex, Mannitol, Citric acid, Colloidal
Silicon Dioxide, Aspartame, and sodium saccharine and shift
through #60 no sieve. Mix all for about 5 Minutes.
9) Add above shifted material through sieve no. and add in step no 7 with continuous stirring.
10) Now mix the Flavor Pineapple to above and stir for 5 minutes.
11) Make up the final volume with corn oil up to 100 Liter and stir further for 10 minutes.
FORMULATION OFCEFUROXIME READY-TO-USE ORAL SUSPENSION

S. No. Material Name Label Claim UOM Quantity Required
1. Cefuroxime Axetil 125 mg/ 5 ml Kg 2.500 *
2. Kyron-T-114 C - Kg 7.500
3. Acetone - Ltr. 30.000
4. Purified Water - Ltr. 70.000
5. Mannitol - Kg 5.000
6. Citric Acid - Kg 0.500
7. Colloidal Silicon Dioxide - Kg 1.000
8. Aspartame - Kg 1.000
9. Sodium Saccharine Kg 0.30
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10.
. \ Butylated Hydroxy toluene - Kg 0.010
11. Sodium Chloride - Kg 0.300
12. Flv. Strawberry - Kg 0.150
13. Corn Oil (Medium Chain Triglyceride) - Ltr. 79.000
Procedure:-
1) DRUG RESIN COMPLEX: - Mix the required quantity of acetone and water and heat up to 40°C.
2) Mix the require quantity of Cefuroxime Axetil and Kyron T-114C accurately and shift through # sieve 40.
3) Slowly add the above mixture in to step 1st with continuous stirring for 20-30 minutes at 40°C on water bath.
4) Observe the pH below 5.5 and stir this solution for another 2.0 hours at 40°C.
5) Dry the taste masked complex in dryer at 40°C until LOD below 5% w/w.
6) Pass the dry drug resin complex through #40 sieve.
7) READY MIX SUSPNSION: Take 50 Litre of Corn oil and add 0.01 Kg of Butylated Hydroxy Toluene stir to get dissolve completely.
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8) Now take Drug Resin Complex, Mannitol, Citric acid, Colloidal
Silicon Dioxide, Aspartame, and sodium saccharine and shift
through #60 no sieve. Mix all for about 5 Minutes.
9) Add above shifted material through sieve no. and add in step no 7
with continuous stirring.
10) Now mix the Flv. Strawberry flavor to above and stir for 5 minutes.
11) Make up the final volume with corn oil up to 100 Liter and stir further for 10 minutes.

We claim:
1) A stable, ready-to-use cephalosporin oral formulation containing
cephalosporin along with at least a pharmaceutical excipient, for the
treatment of bacterial infections.
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2) The oral formulation as claimed in claim 1 may be liquid oral
to
formulation.
3) The cephalosporin as claimed in claim 1 may be selected from the
group comprising cefpodoxime, cefditoren, cefdinir, cefixime,
cefuroxime, cefaclor, ceftibuten, cefprozil, cefepime and cefetamet or
combinations thereof.
4) The cephalosporin as claimed in claim 3 may preferably be
cefuroxime or cefpodoxime.
5) Formulation as claimed in claim 1 does not contain water.
6) The pharmaceutical excipient as claimed in claim 1 may be selected from the group comprising Taste Masking agent, Solvent for taste masking, Taste enhancer, suspending agent, Sweetener, Antioxidant, Flavor and Suspension Base.
7) The process of formulating the formulation of cefpodoxime claimed in claim 3 in the following manner:

S. No. Material Name Label Claim UOM Quantity Required
1. Cefpodoxime Proxetil 100 mg/ 5 ml Kg 2.000 *
2. Kyron T-114 - Kg 6.000
3. Acetone - Ltr. 30.000
4. Purified Water - Ltr. 70.000
5. Mannitol - Kg 5.000
6. Citric Acid - Kg 0.500
7. Colloidal Silicon Dioxide - Kg 1.000
8. Aspartame - Kg 1.000
9. Sodium Saccharine - Kg 0.250
10. Butylated Hydroxy toluene - Kg 0.010
11. Sodium Chloride - Kg 0.200
12. Flv. Pineapple - Kg 0.100
13. Corn Oil (Medium Chain Triglyceride) - Ltr. 84.00
a) DRUG RESIN COMPLEX: - Mix the required quantity of acetone and water.

b) Mix the require quantity of Cefpodoxime Proxetil and Kyron T-114 accurately and shift through # sieve 40.
c) Slowly add the above mixture in to step (a) with continuous stirring for 20-30 minutes.
d) Observe the pH below 5.5 and stir this solution for another 2.0 hours.
e) Dry the taste masked complex in dryer at 40°C until LOD below 5% w/w.
f) Pass the dry drug resin complex through #40 sieve.
g) READY MIX SUSPNSION: Take 50 Litre of Corn oil and add 0.01 Kg of Butylated Hydroxy Toluene stir to get dissolve completely.
h) Now take Drug Resin Complex, Mannitol, Citric acid, Colloidal Silicon Dioxide, Aspartame, and sodium saccharine and shift through #60 no sieve. Mix all for about 5 Minutes.
i) Add above shifted material through sieve no. and add in step (g) with continuous stirring.
j) Now mix the Flavor Pineapple to above and stir for 5 minutes.
k) Make up the final volume with corn oil up to 100 Liter and stir further for 10 minutes.
8) The process of formulating the formulation of cefuroxime claimed in claim 3 in the following manner:

S. No. Material Name Label Claim UOM Quantity Required
1. Cefuroxime Axetil 125 mg/ 5 ml Kg 2.500 *
2. Kyron T-114 C - Kg 7.500
3. Acetone - Ltr. 30.000
4. Purified Water Ltr. 70.000
5. Mannitol - Kg 5.000
6. Citric Acid - Kg 0.500
7. Colloidal Silicon Dioxide - Kg 1.000
8. Aspartame - Kg 1.000
9, Sodium Saccharine - Kg 0.30
10. Butylated Hydroxy toluene - Kg 0.010
11. Sodium Chloride - Kg 0.300
12. Flv. Strawberry - Kg 0.150
13. Corn Oil (Medium Chain Triglyceride) - Ltr. 79.000

DRUG RESIN COMPLEX: - Mix the required quantity of acetone and water and heat up to 40°C.
Mix the require quantity of Cefuroxime Axetil and Kyron T-114C accurately and shift through # sieve 40.
Slowly add the above mixture in to step (a) with continuous stirring for 20-30 minutes at 40°C on water bath. Observe the pH below 5.5 and stir this solution for another 2.0 hours at40°C.
Dry the taste masked complex in dryer at 40°C until LOD below 5% w/w.
Pass the dry drug resin complex through #40 sieve. READY MIX SUSPNSION: Take 50 Litre of Corn oil and add 0.01 Kg of Butylated Hydroxy Toluene stir to get dissolve completely. Now take Drug Resin Complex, Mannitol, Citric acid, Colloidal Silicon Dioxide, Aspartame, and sodium saccharine and shift through #60 no sieve. Mix all for about 5 Minutes. Add above shifted material through sieve no. and add in step no (g) with continuous stirring.
Now mix the Flv. Strawberry flavor to above and stir for 5 minutes.
Make up the final volume with corn oil up to 100 Liter and stir further for 10 minutes.