THE PATENTS ACT, 1970 COMPLETE SPECIFICATION
Section 10
"Cefdinir Oral Suspension.


Abbott Laboratories, a corporation organized and existing under the laws of USA, of Dept 377 BIdg AP6A-1,100 Abbott Park Road, Abbott Park, Illinois 60064-6008 USA..
The following specification particularly describes the nature of this invention and the manner in which it is io be performed:
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CEFDINIR ORAL SUSPENSION
Technical Field
The present invention discloses a novel oral suspension of cefdinir. Also disclosed 5 are methods of preparing the suspension and methods of treatment using the suspension.
Background of the Invention
Omnicef® for oral suspension contains the active ingredient cefdinir, an extended-spectrum, antibiotic in the cephalosporin family. Chemically, cefdinir is 7-[2-(2-
10 ammothiazol-4-yl)-2-hydroxyimmoacetanudo]-3-vinyl-3-cephem-4-carboxylic acid (syn isomer). Cefdinir is active against a wide spectrum of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Hemophilus influenzae, Moraxella catarrhalis, E. coli, Klebsiella pneumoniae, and Proteus mirabilis.
Given the large pediatric population that uses antibiotic suspension products,
15 compliance is a critical issue. The recommended dosage of treatment with a pediatric patient is typically based on the weight of the patient. A 1999 study showed that young patient age was associated with a lower compliance in taking oral antibiotic suspensions (Clinical Therapeutics, 1999,21, 1193-1201). One of the factors cited as contributing to the low compliance rate in the youngest children was technical difficulty in adrninistration of the
20 suspensions (e.g., spillage). In a study of acute otitis media, 53% of children took less than half the prescribed medication (J. Pediatr, 1975; 87:137-141).
Omnicef® for oral suspension is indicated for the treament of pediatric patients with acute bacterial otitis media and pharyngitis/tonsillitis. Omnicef® for oral suspension is delivered to pharmacies as a 4% (4.2% actual) cefdinir by weight powder. Upon
25 reconstitution with water, Omnicef® is administered orally and is currently formulated as a 125 mg/5 mL suspension. In younger pediatrics, a typical dosing of to Oanicef® suspension requires two 5 mL aliquots of the suspension. Administering two consecutive 5 mL aliquots can result in the loss of substantial material due to spillage. Furthermore, high concentration suspensions can show physical stability issues.
30 A high concentration, stable formulation that allows for the administration of a single
aliquot would prove beneficial.
Summary of the Invention
In its principle embodiment the present invention provides a powder for oral 35 suspension of cefdinir comprising greate- than 4.2% by weight of cefdinir.


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Detailed Description of the Invention
In its principle embodiment the present invention provides a powder for oral suspension of cefdinir comprising greater than 4.2% by weight of cefdinir.
In another embodiment the present invention provides a powder for oral suspension of 5 cefdinir comprising between about 6% to about 10% by weight of cefdinir.
In another embodiment the present invention provides a powder for oral suspension of cefdinir comprising at least 8.4% by weight of cefdinir.
In another embodiment the present invention provides a powder for oral suspension of
cefdinir comprising
10 (a) at least 8.4% by weight cefdinir;
(b) a diluent; and
(c) a buffering agent.
In another embodiment the present invention provides a powder for oral suspension of 15 cefdinir comprising:
(a) about 8.4% by weight cefdinir;
(b) about 89.2% by weight diluent;
(c) about 0.26% by weight buffering agent;
(d) about 0.16% by weight preservative;
20 (e) about 0.33% by weight viscosity enhancer;
(f) about 1.31 % by weight flavoring agent;
(g) about 0.07% glidant; and (h) about 0.35% lubricant
25 In another embodiment the present invention provides an powder for oral suspension
of cefdinir comprising;
(a) about 8.36% by weight cefdinir;
(b) about 89.16% by weight sucrose;
(c) about 0.16% by weight citric acid;
30 (d) about 0.10% by weight sodium citrate;
(e) about 0.16% by weight sodium benzoate;
(f) about 0.16% by weight xantham gum;
(g) about 0.16% by weight guar gum;
(h) about 1.31% by weight flavoring agent:
35 (i) about 0.06% colloidal silicon dioxide; and
(j) about 0,35% magnesium stearate.
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The present invention also teaches a method of treating acute bacterial otitis media, pharyngitis and tonsillitis with a oral-suspension of cefdinir wherein said suspension is made by reconstituting a powder comprising greater than 4.2% by weight of cefdinir.
A further embodiment of the present invention teaches a method of treating acute
5 bacterial otitis media, pharyngitis and tonsillitis with a oral suspension of cefdinir wherein
said suspension is made by reconstituting a powder comprising at least 8.4% cefdinir.
All publications, issued patents, and patent applications cited herein are hereby
incorporated by reference in their entirety. In the case of inconsistencies, the present
disclosure, including definitions, will prevail.
10 As used herein, the singular forms "a", "an", and "the" include plural reference unless
the context clearly dictates otherwise.
As used in the present specification the following terms have the meanings indicated: The term "buffering agent," as used herein, refers to an agent or a mixture of agents that can maintain the original acidity or basicity of a composition. Representative buffering 15 agents include, but are not limited to, citric acid, sodium citrate, sodium phosphate, potassium citrate, and mixtures thereof. A preferred buffering agent of the present invention is a mixture of citric acid and sodium citrate.
The term "diluent," as used herein, refers to an agent or mixture of agents that when
added to a formulation makes that formulation thinner or less concentrated and may also
20 improve manufacturabihty. Diluents of the present invention can also serve other functions.
For example, a diluent can also serve as a sweetener. Representative diluents include, but are
not limited to, sucrose, sorbitol, xylitol, dextrose, fructose, malitol, sugar potassium,
aspartame, saccharin, saccharin sodium, and mixtures thereof. A preferred diluent of the;
present invention is sucrose.
25 The term "flavoring agent," as used herein, refers to an agent or a mixture of agents
that adds flavor to a mixture. Representative flavoring agents include, but are not limited to, artificial strawberry flavor and artificial cream flavor.
The term "glidant," as used herein, refers to an agent or a mixture of agents that _, facilitates the flow of powders in the manufacturing process. Representative glidants include, 30 but are not limited to, colloidal silicon dioxide, talc, fumed silica, magnesium stearate, calcium stearate, magnesium trisilicate, powdered cellulose, starch, tribasic calcium phosphate, and mixtures thereof A preferred glidant of the present invention is colloidal silicon dioxide.
The term "lubricant," as used herein refers to an agent or a mixture of agents that 35 lessen'- or prevents friction. Representative lubricants include, but are not limited to,
magnesium stearate, calcium stearate, zinc stearate, magnesium oxide, stearic acid, sodium stearyl fumarate, sodium lauryl stearate, hydrogenated vegetable oil, com starch, colloidal


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silicon dioxide, talc, and mixtures thereof. A preferred lubricant of the present invention is magnesium stearate.
The term "preservative," as used herein, refers to an agent or mixture of agents that is used to protect a composition against antimicrobial (e.g., yeast, mold, bacteria) activity. 5 Representative preservatives include, but are not limited to, sodium benzoate, benzoic acid, ediylenediarninetetraacetic acid, sorbic acid, benzethonium chloride, benzalkonium chloride, bronopol, butyl paraben, methyl paraben, ethylparaben, propyl paraben, thiomerosol, sodium propionate, chlorhexidine, chlorobutanol, chlorocresol, cresol, imidurea, phenol, phenylmercuric salts, potassium sorbate, propylene glycol, and mixtures thereof. A preferred
10 preservative of the present invention is sodium benzoate.
The term "viscosity enhancer," as used herein, refers to an agent or a mixture of agents that increases the thickness of a liquid thereby making it slow to flow. For example, in a suspension a viscosity enhancer will help to keep the active ingredient suspended to allow accurate dosing. Representative viscosity enhancers include, but are not limited to,
15 xantham gum, guar gum, acacia, povidone, alginic acid, sodium alginate, propylene glycol alginate, carbomer, carboxymethylcellulose calcium, carboxymethylcellulose sodium, ethylcellulose, gelatin, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polydextrose, carrageenan, methylcellulose, sucrose, sorbitol, xylitol, dextrose, fructose, malitol, sugar, sodium alginate, tragacanth, hydroxypropyl methylcellulose, bentonite, a
20 polyvinyl alcohol, cetearyl alcohol, colloidal silicon dioxide, and mixtures thereof. A
preferred viscosity enhancer of the present invention is a mixture of xantham gum and guar gum.
Cefdinir can be prepared according to the procedures described in tJ.S. Patent Serial No. 4,935,507, issued June 19,1990 and U.S. Patent Serial No. 4,559,334, issued December
25 17,1985, both herein fully incorporated by reference.
Example 1 shows the percentage amounts used in the preparation of an8% cefxtilinir oral powder formulation. As mentioned earlier, the current marketed Omnicef® for suspension is a 4% (4.2% actual) cefdinir powder by weight. The 8% formula was bioequivalent to the Omnicef® for oral suspension product.
30 Example 1
Ingredient Percent Used in 8% Formulation
Cefdinir 8.361
Sucrose, NF Extra Fine Granulated 89.157
Citric Acid, USP Anhydrous Powder 0.164
Sodium Citrate, USP Anhydrous Powder 0.098
Sodium Benzoate, NF 0.164
Xanthan Gum,NF (Xantural 75) 0.164
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Guar Gum, NF 0.164
"Artificial Cream Flavor 610979U-PFW 0.131
Colloidal Silicon Dioxide Anhydrous, NF 0.066
Artificial Strawberry Flavor 1 0.393
Artificial Strawberry Flavor 2 0.787
Magnesium Stearate, NF 0.351
Examples 2 and 3 show percentage amounts that can be used in the preparation of 6% and 10% cefdinir oral powder formulations.
Example 2

Ingredient Percent Used in 6% Formulation
Cefdinir 6.000
Sucrose, NF Extra Fine Granulated 91.518
Citric Acid, USP Anhydrous Powder 0.164
Sodium Citrate, USP Anhydrous Powder 0.098
Sodium Benzoate, NF 0.164
Xanthan Gum, NF (Xantural 75) 0.164
Guar Gum, NF 0.164
Artificial Cream Flavor 610979U-PFW 0.131
Colloidal Silicon Dioxide Anhydrous, NF 0.066
Artificial Strawberry Flavor 1 0.393
Artificial Strawberry Flavor 2 0.787
Magnesium Stearate, NF 0.351
Example 3

Ingredient Percent Used in 10% Formulation
Cefdinir 10.000
Sucrose, NF Extra Fine Granulated 185.04
Citric Acid, USP Anhydrous Powder 0.328
Sodium Citrate, USP Anhydrous Powder 0.196
Sodium Benzoate, NF 0.328
Xanthan Gum, NF (Xantural 75) 0.328
Guar Gum, NF 0.328
Artificial Cream Flavor 610979U-PFW 0.262
Colloidal Silicon Dioxide Anhydrous, NF 0.130
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Artificial Strawberry Flavor 1 0.790
Artificial Strawberry Flavor 2 1.570
Magnesium Stearate, NF 0.702
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WHAT IS CLAIMED IS
1. A powder for oral suspension comprising greater than 4.2% by weight of cefdinir.
2. A powder for oral suspension comprising about 6% to about 10% by weight of cefdinir-
3. A powder for oral suspension comprising at least 8.4% by weight cefdinir.
4. A powder for oral suspension comprising

(a) at least 8.4% by weight cefdinir;
(b) a diluent; and
(c) a buffering agent.
, 5. A powder for oral suspension of claim 4 wherein the diluent is selected from the group consisting of sucrose, sorbitol, xylitol, dextrose, fructose, malitol, sugar potassium, aspartame, saccharin, saccharin sodium, and mixtures thereof-
6. A powder for oral suspension of claim 5 wherein the diluent is sucrose.
7. A powder for oral suspension of claim 4 wherein the buffering agent is selected from the group consisting of citric acid, sodium citrate, sodium phosphate, potassium citrate, and mixtures thereof.
5. A powder for oral suspension of claim 7 wherein the buffering agent is a mixture of
citric acid and sodium citrate.
9. A powder for oral suspension comprising:
(a) about 8.4% by weight cefdinir;
(b) about 89.2% by weight diluent;
(c) about 0.26% by weight buffering agent;
(d) about 0.16%by weight preservative;
(e) about 0.33% by weight viscosity enhancer;
(f) about 1,31% by weight flavoring agent;
(g) about 0.07% glidant; and (h) about 0.35% lubricant.


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10. A powder for oral suspension of claim 9 wherein the diluent is selected from the group consisting of sucrose, sorbitol, xylitol, dextrose, fructose, malitol, sugar potassium, aspartame, saccharin, saccharin sodium, and mixtures thereof.
11. A powder for oral suspension of claim 10 wherein the diluent is sucrose.
12. A powder for oral suspension of claim 9 wherein the buffering agent is selected from the group consisting of citric acid, sodium citrate, sodium phosphate, potassium citrate, and mixtures thereof.
13. A powder for oral suspension of claim 12 wherein the buffering agent is a mixture of citric acid and sodium citrate.
14. A powder for oral suspension of claim 9 wherein the preservative is selected from the group consisting of sodium benzoate, benzoic acid, ethylenediaminetetraacetic acid, sorbic acid, benzethonium chloride, benzalkonium chloride, bronopol, butyl paraben, methyl paraben, ethylparaben, propyl paraben, thiomerosol, sodium propionate, chlorhexidine, chlorobutanol, chlorocresol, cresol, imidurea, phenol, phenylmercuric salts, potassium sorbate, propylene glycol, and mixtures thereof.
15. A powder for oral suspension of claim 14 wherein the preservative is sodium benzoate.
16. A powder for oral suspension of claim 9 wherein the viscosity enhancing agent is -selected from the group consisting of xantham gum, .guar gum, acacia, povidone, algiaic acid, sodium alginate, propylene glycol alginate, carbomer, carboxymethylcellulose calcium, carboxymethylcellulose sodium, ethylcellulose, gelatin, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polydextrose, carrageenan, methylcellulose, sucrose, sorbitol, xylitol, dextrose, fructose, malitol, sugar, sodium alginate, tragacanth, hydroxypropyl methylcellulose, bentonite, a polyvinyl alcohol, cetearyl alcohol, colloidal silicon dioxide, and mixtures thereof.
17. A powder for oral suspension of claim 16 wherein the viscosity enhancing agent is a mixture of xantham gum and guar gum.


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18. A powder for oral suspension of claim 9 wherein the glidant is selected from the group consisting of colloidal silicon dioxide, talc, fumed silica, magnesium stearate, calcium stearate, magnesium trisilicate, powdered cellulose, starch, tribasic calcium phosphate, and mixtures thereof.
19. A powder for oral suspension of claim 18 wherein the glidant is colloidal silicon dioxide.
20. A powder for oral suspension of claim 9 wherein the lubricant is selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, magnesium oxide, stearic acid, sodium stearyl fumarate, sodium lauryl stearate, hydrogenated vegetable oil, corn starch, colloidal silicon dioxide, talcy and mixtures thereof.
21. Apowder for oral suspension of claim 20 wherein the lubricant is magnesium stearate:
22. A powder for oral suspension comprising:
(a) about 8.36% by weight cefdinir;
(b) about 89.16% by weight sucrose;
(c) about 0.16% by weight citric acid;
(d) about 6.10% by weight sodium citrate; (e)-about046% by weight sodium benzoate;;

(f) about 0.16% by weight xantham gum;
(g) about 0.16% by weight guar gum;
(h) about 131% by weight flavoring agent; (i) aboutO.06% colloidal silicon-dioxide; and (j) about 0.35% magnesium stearate.
23. Amethod of treating acute bacterial otitis media, pharyngitis and tonsillitis with a oral suspension of cefdinir wherein said suspension is made by reconstituting a powder comprising greater than/4;2% by weight of cefdinir.
24. Amethod of treating acute bacterial otitis media, pharyngitis and tonsillitis with a oral suspension of cefdinir wherein said suspension is made by reconstituting a powder comprising at least 8.4% cefdinir.

Dated this 04th day of June 2008
Of Anand And-AnanAdvocates Attorney for the Applicant