US 2008O139528A1
(19) United States
(12) Patent Application Publication (10) Pub. No.: US 2008/0139528A1
Pujara (43) Pub. Date: Jun. 12, 2008
(54) CEFDINIRORAL SUSPENSION Publication Classification
(76) Inventor: Chetan P. Pujara, Gurnee, IL (US) (51) Int. Cl.
A 6LX 3L/397 (2006.01)
Correspondence Address: A6IP3L/04 (2006.01)
PAUL. D. YASGER
ABBOTT LABORATORIES
100 ABBOTT PARK ROAD, DEPT. 377/AP6A (52) U.S. Cl. ................................................... S14/210.05
ABBOTT PARK, IL 60064-6008
(21) Appl. No.: 10/991,909
(22) Filed: Nov. 18, 2004 (57) ABSTRACT
O O The present invention discloses a novel powder for oral sus
Related U.S. Application Data pension of cefdinir. Also disclosed are methods of preparing
(60) Provisional application No. 60/528,314, filed on Dec. the Suspension and methods of treatment using the Suspen
10, 2003. Sion.
US 2008/O 139528 A1 Jun. 12, 2008
CEFDNR ORAL SUSPENSION 0010. In another embodiment the present invention pro
vides a powder for oral Suspension of cefdinir comprising at
least 8.4% by weight of cefdinir.
0001. This application claims priority from U.S. Provi 0011. In another embodiment the present invention pro
sional Patent Application Ser. No. 60/528,314, filed Dec. 10, vides a powder for oral Suspension of cefdinir comprising
2003, incorporated herein by reference. 0012 (a) at least 8.4% by weight cefdinir:
(0013 (b) a diluent; and
TECHNICAL FIELD 0014 (c) a buffering agent.
0002 The present invention discloses a novel oral suspen 0015. In another embodiment the present invention pro
sion of cefdinir. Also disclosed are methods of preparing the vides a powder for oral Suspension of cefdinir comprising:
Suspension and methods of treatment using the Suspension. 0016 (a) about 8.4% by weight cefdinir:
(0017 (b) about 89.2% by weight diluent;
BACKGROUND OF THE INVENTION 0018 (c) about 0.26% by weight buffering agent;
(0019 (d) about 0.16% by weight preservative:
0003 OmnicefR for oral suspension contains the active 0020 (e) about 0.33% by weight viscosity enhancer;
ingredient cefdinir, an extended-spectrum, antibiotic in the 0021 (f) about 1.31% by weight flavoring agent;
cephalosporin family. Chemically, cefdinir is 7-2-(2-ami 0022 (g) about 0.07% glidant; and
nothiazol-4-yl)-2-hydroxyiminoacetamido-3-vinyl-3-
cephem-4-carboxylic acid (syn isomer). Cefdinir is active (0023 (h) about 0.35% lubricant.
against a wide spectrum of bacteria, including Staphylococ 0024. In another embodiment the present invention pro
cus aureus, Streptococcus pneumoniae, Streptococcus pyo vides an powder for oral Suspension of cefdinir comprising:
genes, Hemophilus influenzae, Moraxella Catarrhalis, E. coli, (0025 (a) about 8.36% by weight cefdinir:
Klebsiella pneumoniae, and Proteus mirabilis. (0026 (b) about 89.16% by weight sucrose;
0004 Given the large pediatric population that uses anti (0027 (c) about 0.16% by weight citric acid:
biotic Suspension products, compliance is a critical issue. The 0028 (d) about 0.10% by weight sodium citrate;
recommended dosage of treatment with a pediatric patient is 0029 (e) about 0.16% by weight sodium benzoate:
typically based on the weight of the patient. A 1999 study 0030 (f) about 0.16% by weight xantham gum;
showed that young patient age was associated with a lower 0031 (g) about 0.16% by weight guar gum;
compliance in taking oral antibiotic suspensions (Clinical 0032. (h) about 1.31% by weight flavoring agent;
Therapeutics, 1999, 21, 1193-1201). One of the factors cited 0033 (i) about 0.06% colloidal silicon dioxide; and
as contributing to the low compliance rate in the youngest 0034 () about 0.35% magnesium stearate.
children was technical difficulty in administration of the sus 0035. The present invention also teaches a method of treat
pensions (e.g., spillage). In a study of acute otitis media, 53% ing acute bacterial otitis media, pharyngitis and tonsillitis
of children took less than half the prescribed medication (J with a oral Suspension of cefdinir wherein said Suspension is
Pediatr. 1975; 87:137-141). made by reconstituting a powder comprising greater than
0005. OmnicefR for oral suspension is indicated for the 4.2% by weight of cefdinir.
treatment of pediatric patients with acute bacterial otitis 0036. A further embodiment of the present invention
media and pharyngitis/tonsillitis. OmnicefR for oral Suspen teaches a method of treating acute bacterial otitis media,
sion is delivered to pharmacies as a 4% (4.2% actual) cefdinir pharyngitis and tonsillitis with a oral Suspension of cefdinir
by weight powder. Upon reconstitution with water, wherein said Suspension is made by reconstituting a powder
OmnicefR is administered orally and is currently formulated comprising at least 8.4% cefdinir.
as a 125 mg/5 mL suspension. In younger pediatrics, a typical 0037 All publications, issued patents, and patent applica
dosing of Omnicef R. Suspension requires two 5 mL aliquots tions cited herein are hereby incorporated by reference in
of the Suspension. Administering two consecutive 5 mL ali their entirety. In the case of inconsistencies, the present dis
quots can result in the loss of Substantial material due to closure, including definitions, will prevail.
spillage. Furthermore, high concentration Suspensions can 0038. As used herein, the singular forms “a”, “an', and
show physical stability issues. “the include plural reference unless the context clearly dic
0006. A high concentration, stable formulation that allows tates otherwise.
for the administration of a single aliquot would prove benefi 0039. As used in the present specification the following
cial. terms have the meanings indicated:
SUMMARY OF THE INVENTION
0040. The term “buffering agent, as used herein, refers to
an agent or a mixture of agents that can maintain the original
0007. In its principle embodiment the present invention acidity or basicity of a composition. Representative buffering
provides a powder for oral Suspension of cefdinir comprising agents include, but are not limited to, citric acid, sodium
greater than 4.2% by weight of cefdinir. citrate, Sodium phosphate, potassium citrate, and mixtures
thereof. A preferred buffering agent of the present invention is
DETAILED DESCRIPTION OF THE INVENTION a mixture of citric acid and Sodium citrate.
0041. The term "diluent, as used herein, refers to an agent
0008. In its principle embodiment the present invention or mixture of agents that when added to a formulation makes
provides a powder for oral Suspension of cefdinir comprising that formulation thinner or less concentrated and may also
greater than 4.2% by weight of cefdinir. improve manufacturability. Diluents of the present invention
0009. In another embodiment the present invention pro can also serve other functions. For example, a diluent can also
vides a powder for oral Suspension of cefdinir comprising serve as a Sweetener. Representative diluents include, but are
between about 6% to about 10% by weight of cefdinir. not limited to, Sucrose, Sorbitol. Xylitol, dextrose, fructose,
US 2008/O 139528 A1 Jun. 12, 2008
malitol, Sugar potassium, aspartame, Saccharin, saccharin pension is a 4% (4.2% actual) cefdinirpowderby weight. The
sodium, and mixtures thereof. A preferred diluent of the 8% formula was bioequivalent to the OmnicefR for oral
present invention is sucrose. Suspension product.
0042. The term “flavoring agent, as used herein, refers to Example 1
an agent or a mixture of agents that adds flavor to a mixture.
Representative flavoring agents include, but are not limited 0049
to, artificial strawberry flavor and artificial cream flavor.
0043. The term "glidant, as used herein, refers to an agent
or a mixture of agents that facilitates the flow of powders in Percent Used in
the manufacturing process. Representative glidants include, Ingredient 8%. Formulation
but are not limited to, colloidal silicon dioxide, talc, fumed Cefinir 8.361
silica, magnesium Stearate, calcium Stearate, magnesium tri Sucrose, NF Extra Fine Granulated 89.157
Citric Acid, USP Anhydrous Powder O.164
silicate, powdered cellulose, starch, tribasic calcium phos Sodium Citrate, USP Anhydrous Powder O.098
phate, and mixtures thereof. A preferred glidant of the present Sodium Benzoate, NF O.164
invention is colloidal silicon dioxide. Xanthan Gum, NF (Xantural 75) O.164
Guar Gum, NF O.164
0044. The term “lubricant, as used herein refers to an Artificial Cream Flavor 610979U-PFW O.131
agent or a mixture of agents that lessens or prevents friction. Colloidal Silicon Dioxide Anhydrous, NF O.O66
Artificial Strawberry Flavor 1 O.393
Representative lubricants include, but are not limited to, mag Artificial Strawberry Flavor 2 0.787
nesium Stearate, calcium Stearate, Zinc Stearate, magnesium Magnesium Stearate, NF O.351
oxide, Stearic acid, sodium Stearyl fumarate, sodium lauryl
Stearate, hydrogenated vegetable oil, corn starch, colloidal 0050 Examples 2 and 3 show percentage amounts that can
silicon dioxide, talc, and mixtures thereof. A preferred lubri be used in the preparation of 6% and 10% cefdinir oral pow
cant of the present invention is magnesium Stearate. der formulations.
0045. The term “preservative as used herein, refers to an Example 2
agent or mixture of agents that is used to protect a composi
tion against antimicrobial (e.g., yeast, mold, bacteria) activ 0051
ity. Representative preservatives include, but are not limited
to, Sodium benzoate, benzoic acid, ethylenediaminetetraace Percent Used in
tic acid, Sorbic acid, benzethonium chloride, benzalkonium Ingredient 6%. Formulation
chloride, bronopol, butyl paraben, methyl paraben, ethylpa
Cefinir [Link]
raben, propyl paraben, thiomerosol, Sodium propionate, chlo Sucrose, NF Extra Fine Granulated 91.518
rhexidine, chlorobutanol, chlorocresol, cresol, imidurea, phe Citric Acid, USP Anhydrous Powder O.164
nol, phenylmercuric salts, potassium Sorbate, propylene Sodium Citrate, USP Anhydrous Powder O.098
glycol, and mixtures thereof. A preferred preservative of the Sodium Benzoate, NF O.164
Xanthan Gum, NF (Xantural 75) O.164
present invention is sodium benzoate. Guar Gum, NF O.164
0046. The term “viscosity enhancer, as used herein, refers Artificial Cream Flavor 610979U-PFW O.131
Colloidal Silicon Dioxide Anhydrous, NF O.O66
to an agent or a mixture of agents that increases the thickness Artificial Strawberry Flavor 1 O.393
of a liquid thereby making it slow to flow. For example, in a Artificial Strawberry Flavor 2 0.787
Suspension a viscosity enhancer will help to keep the active Magnesium Stearate, NF O.351
ingredient Suspended to allow accurate dosing. Representa
tive viscosity enhancers include, but are not limited to, Xan
tham gum, guar gum, acacia, poVidone, alginic acid, Sodium Example 3
alginate, propylene glycol alginate, carbomer, carboxymeth
ylcellulose calcium, carboxymethylcellulose Sodium, ethyl 0.052
cellulose, gelatin, ethylcellulose, hydroxyethyl cellulose,
hydroxypropyl cellulose, polydextrose, carrageenan, methyl
cellulose. Sucrose, Sorbitol, Xylitol, dextrose, fructose, mali Percent Used in
tol, Sugar, Sodium alginate, tragacanth, hydroxypropyl meth Ingredient 10% Formulation
ylcellulose, bentonite, a polyvinyl alcohol, cetearyl alcohol, Cefinir [Link]
colloidal silicon dioxide, and mixtures thereof. A preferred Sucrose, NF Extra Fine Granulated 185.04
Viscosity enhancer of the present invention is a mixture of Citric Acid, USP Anhydrous Powder O.328
Sodium Citrate, USP Anhydrous Powder O.196
Xantham gum and guar gum. Sodium Benzoate, NF O.328
0047 Cefdinir can be prepared according to the proce Xanthan Gum, NF (Xantural 75) O.328
dures described in U.S. Pat. Ser. No. 4,935,507, issued Jun. Guar Gum, NF O.328
Artificial Cream Flavor 610979U-PFW O.262
19, 1990 and U.S. Pat. Ser. No. 4,559,334, issued Dec. 17, Colloidal Silicon Dioxide Anhydrous, NF O.130
1985, both herein fully incorporated by reference. Artificial Strawberry Flavor 1 O.790
Artificial Strawberry Flavor 2 1570
0048 Example 1 shows the percentage amounts used in Magnesium Stearate, NF O.702
the preparation of an 8% cefdinir oral powderformulation. As
mentioned earlier, the current marketed OmnicefR for sus
US 2008/O 139528 A1 Jun. 12, 2008
What is claimed is: chlorobutanol, chlorocresol, cresol, imidurea, phenol, phe
1. A powder for oral Suspension comprising greater than nylmercuric salts, potassium Sorbate, propylene glycol, and
4.2% by weight of cefdinir. mixtures thereof.
2. A powder for oral Suspension comprising about 6% to 15. A powder for oral suspension of claim 14 wherein the
about 10% by weight of cefdinir. preservative is sodium benzoate.
3. A powder for oral Suspension comprising at least 8.4% 16. A powder for oral suspension of claim 9 wherein the
by weight cefdinir. Viscosity enhancing agent is selected from the group consist
4. A powder for oral Suspension comprising ing of Xantham gum, guar gum, acacia, poVidone, alginic
(a) at least 8.4% by weight cefdinir: acid, sodium alginate, propylene glycol alginate, carbomer,
carboxymethylcellulose calcium, carboxymethylcellulose
(b) a diluent; and Sodium, ethylcellulose, gelatin, ethylcellulose, hydroxyethyl
(c) a buffering agent. cellulose, hydroxypropyl cellulose, polydextrose, carrag
5. A powder for oral suspension of claim 4 wherein the eenan, methylcellulose, Sucrose, Sorbitol. Xylitol, dextrose,
diluent is selected from the group consisting of Sucrose, Sor fructose, malitol, Sugar, sodium alginate, tragacanth, hydrox
bitol. Xylitol, dextrose, fructose, malitol, Sugar potassium, ypropyl methylcellulose, bentonite, a polyvinyl alcohol, cet
aspartame, saccharin, saccharin Sodium, and mixtures earyl alcohol, colloidal silicon dioxide, and mixtures thereof.
thereof. 17. A powder for oral suspension of claim 16 wherein the
6. A powder for oral suspension of claim 5 wherein the Viscosity enhancing agent is a mixture of Xantham gum and
diluent is Sucrose. guar gun.
7. A powder for oral suspension of claim 4 wherein the 18. A powder for oral suspension of claim 9 wherein the
buffering agent is selected from the group consisting of citric glidant is selected from the group consisting of colloidal
acid, sodium citrate, Sodium phosphate, potassium citrate, silicon dioxide, talc, fumed silica, magnesium Stearate, cal
and mixtures thereof. cium Stearate, magnesium trisilicate, powdered cellulose,
8. A powder for oral suspension of claim 7 wherein the starch, tribasic calcium phosphate, and mixtures thereof.
buffering agent is a mixture of citric acid and Sodium citrate. 19. A powder for oral suspension of claim 18 wherein the
9. A powder for oral Suspension comprising: glidant is colloidal silicon dioxide.
(a) about 8.4% by weight cefdinir: 20. A powder for oral suspension of claim 9 wherein the
(b) about 89.2% by weight diluent; lubricant is selected from the group consisting of magnesium
(c) about 0.26% by weight buffering agent; Stearate, calcium Stearate, Zinc Stearate, magnesium oxide,
(d) about 0.16% by weight preservative; Stearic acid, sodium Stearyl fumarate, sodium lauryl Stearate,
(e) about 0.33% by weight viscosity enhancer; hydrogenated vegetable oil, corn Starch, colloidal silicon
(f) about 1.31% by weight flavoring agent; dioxide, talc, and mixtures thereof.
(g) about 0.07% glidant; and 21. A powder for oral suspension of claim 20 wherein the
lubricant is magnesium Stearate.
(h) about 0.35% lubricant. 22. A powder for oral Suspension comprising:
10. A powder for oral suspension of claim 9 wherein the (a) about 8.36% by weight cefdinir:
diluent is selected from the group consisting of Sucrose, Sor (b) about 89.16% by weight sucrose;
bitol. Xylitol, dextrose, fructose, malitol, Sugar potassium, (c) about 0.16% by weight citric acid;
aspartame, saccharin, saccharin Sodium, and mixtures (d) about 0.10% by weight sodium citrate;
thereof. (e) about 0.16% by weight sodium benzoate:
11. A powder for oral suspension of claim 10 wherein the (f) about 0.16% by weight xantham gum;
diluent is Sucrose. (g) about 0.16% by weight guar gum,
12. A powder for oral suspension of claim 9 wherein the (h) about 1.31% by weight flavoring agent;
buffering agent is selected from the group consisting of citric (i) about 0.06% colloidal silicon dioxide; and
acid, sodium citrate, Sodium phosphate, potassium citrate, 23. A method of treating acute bacterial otitis media, phar
and mixtures thereof. yngitis and tonsillitis with a oral Suspension of cefdinir
13. A powder for oral suspension of claim 12 wherein the wherein said Suspension is made by reconstituting a powder
buffering agent is a mixture of citric acid and Sodium citrate. comprising greater than 4.2% by weight of cefdinir.
14. A powder for oral suspension of claim 9 wherein the 24. A method of treating acute bacterial otitis media, phar
preservative is selected from the group consisting of sodium yngitis and tonsillitis with a oral Suspension of cefdinir
benzoate, benzoic acid, ethylenediaminetetraacetic acid, Sor wherein said Suspension is made by reconstituting a powder
bic acid, benzethonium chloride, benzalkonium chloride, comprising at least 8.4% cefdinir.
bronopol, butyl paraben, methyl paraben, ethylparaben, pro
pyl paraben, thiomerosol, Sodium propionate, chlorhexidine, c c c c c
