Wo 2010/096551 A2

Home , Meglumine

(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 26 August 2010 (26.08.2010) WO 2010/096551 A2

(51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/4725 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/US2010/024576 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, 18 February 2010 (18.02.2010) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (25) Filing Language: English NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/153,463 18 February 2009 (18.02.2009) US (84) Designated States (unless otherwise indicated, for every 61/25 1,475 14 October 2009 (14.10.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): RIB-X ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, PHARMACEUTICALS, INC. [-/US]; 300 George TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, Street, Suite 301, New Haven, CT 065 11 (US). ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, (72) Inventors; and TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (75) Inventors/Applicants (for US only): LI, Danping ML, MR, NE, SN, TD, TG). [US/US]; 4 Colonial Court, Middlebury, CT (US). BU- RAK, Eric, S. [US/US]; 51 Bone Mill Road, East Had- Declarations under Rule 4.17: dam, CT 06423 (US). DRESBACK, David, S. [US/US]; — of inventorship (Rule 4Λ 7(iv)) 2 1 Elm Street, Stonington, CT 06378 (US). Published: (74) Agents: ELRIFI, Ivor, R. et al; Mintz Levin Cohn Fer ris Glovsky And Popeo, P.C , One Finnancial Center, — without international search report and to be republished Boston, MA 021 11 (US). upon receipt of that report (Rule 48.2(g))

(54) Title: ANTIMICROBIAL COMPOSITIONS Figure 3

Delafloxacin Capsules in 2-Step Dissolution, 45 mg/50 mL

ith arginine

ith FVP)

TPGS Solution

Drug)

Time (min)

(57) Abstract: The present invention relates to pharmaceutical compositions comprising a quinolone carboxylic acid compound and an absorption enhancer. In further embodiments, the compositions further comprise a basifer or a crystallization inhibitor, or both a basifϊer and a crystallization inhibitor. These compositions are useful for treating, preventing, or reducing the risk of infec tion. ANTIMICROBIAL COMPOSITIONS

RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Patent Application No. 61/251,475, filed October 14, 2009 and U.S. Patent Application No. 61/153,463, filed February 18, 2009, the disclosures of which are incorporated by reference herein.

FIELD OF THE INVENTION The present invention relates to pharmaceutical compositions comprising a quinolone carboxylic acid compound and an absorption enhancer. In further embodiments, these compositions further comprise a basifer or a crystallization inhibitor, or both a basifier and a crystallization inhibitor. These compositions can be formulated for administration via various routes, including oral administration. These compositions are useful for treating, preventing, or reducing the risk of infection.

BACKGROUND An appropriate pharmaceutical carrier system is generally a requirement for the safe and effective delivery of a pharmaceutical drug active. The entire pharmaceutical composition, i.e., the pharmaceutical drug active formulated in a pharmaceutical carrier, can affect the bioavailability and also the pharmacokinetics and pharmacodynamics of the drug active. It is therefore important that a pharmaceutical composition be carefully developed and manufactured to deliver the desired pharmaceutical drug active in a safe and effective manner. The delivery of antimicrobial agents for treating or preventing microbial infections can present special challenges. To provide therapeutic efficacy, it is generally desired that the antimicrobial agent be administered to the patient to achieve systemic concentrations in the bloodstream or target organs above a minimum inhibitory concentration (MIC) for a sufficient time against the particular microbial organism or organisms being targeted. Consequently, an antimicrobial agent that otherwise exhibits an effective antimicrobial profile in vitro can be ineffective, or even harmful, unless properly formulated for in vivo administration. When formulating pharmaceutical compositions for oral administration, particularly antimicrobial compositions such as antibiotics, it is important to maximize the delivery of the pharmaceutical active. The reasons for maximizing this delivery is to increase the absorption or bioavailability of the pharmaceutical active and to reduce the amount of the pharmaceutical active remaining in the gastrointestinal tract. By maximizing absorption or bioavailability, more of the pharmaceutical active is transported into the bloodstream and organs of the subject patient for targeting an infection and less of the pharmaceutical active remains, which can cause untoward gastrointestinal side effects such as diarrhea or encourage the growth of resistant, harmful gastrointestinal microorganisms such as Clostridium difficile. The present invention addresses the foregoing and other needs.

BRIEF DESCRIPTION OF THE FIGURES FIG. 1 shows a powder X-ray diffraction pattern of crystalline D-glucitol, 1-deoxy-l- (methylamino)-, l-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-h- ydroxyazetidin- 1-yl)-4-oxo-3-quinolinecarboxylate (salt). FIG. 2 shows a powder X-ray diffraction pattern of crystalline D-glucitol, 1-deoxy-l- (methylamino)-, l-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-h- ydroxyazetidin- 1-yl)-4-oxo-3-quinolinecarboxylate trihydrate (salt). FIG. 3 shows the two-step dissolution of delafloxacin meglumine capsules used in a dog study. FIG. 4 shows the two-step dissolution profile of delafloxacin meglumine formulations used in a dog study.

SUMMARY OF THE INVENTION The present invention relates to antimicrobial compositions and more specifically compositions of quinolone carboxylic acid compounds. The present invention relates to a pharmaceutical composition comprising a quinolone carboxylic acid compound or a pharmaceutically acceptable salt or ester thereof, and an absorption enhancer. In further embodiments, the compositions further comprise a basifer or a crystallization inhibitor, or both a basifϊ er and a crystallization inhibitor. These compositions can be formulated for administration via various routes, including oral administration. These compositions are useful for treating, preventing, or reducing the risk of infection.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a pharmaceutical composition comprising a quinolone carboxylic acid compound or a pharmaceutically acceptable salt or ester thereof, and an absorption inhibitor. In further embodiments, these compositions further comprise a basifer or a crystallization inhibitor, or both a basifϊ er and a crystallization inhibitor. These compositions are useful for treating, preventing, or reducing the risk of infection. In one embodiment, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, and (b) an absorption enhancer. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, and (b) an absorption enhancer. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a basifϊ er. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b)an absorption enhancer, and (c) a basifϊ er. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a crystallization inhibitor. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a crystallization inhibitor. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a - A- pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, (c) a basifϊ er, and (d) a crystallization inhibitor. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, (c) a basifϊ er, and (d) a crystallization inhibitor. In other embodiments, the present invention relates to a pharmaceutical composition comprising (that is in the form of) a dispersion. In other embodiments, the present invention relates to a pharmaceutical composition comprising (that is in the form of) a dry mixture. In other embodiments, the present invention relates to a pharmaceutical composition comprising (that is in the form of) a tablet. In other embodiments, the present invention relates to a pharmaceutical composition comprising (that is in the form of) a capsule. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said absorption enhancer is an alkoxylated tocopheryl ester. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said alkoxylated tocophyerl ester is an alkoxylated tocopheryl monoester. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said alkoxylated tocopheryl monoester is an alkoxylated tocopheryl monosuccinate. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said alkoxylated tocopheryl ester is an ethoxylated tocopheryl ester. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said alkoxylated tocopheryl ester is vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said quinolone carboxylic acid compound corresponds to the following structure

wherein R1 represents a hydrogen atom or a carboxyl protective group; R2 represents a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; R3 represents a hydrogen atom or a halogen atom; R4 represents a hydrogen atom or a halogen atom; R5 represents a halogen atom or an optionally substituted saturated cyclic amino group; R6 represents a hydrogen atom, a halogen atom, a nitro group, or an optionally protected amino group; X, Y and Z may be the same or different and respectively represent a nitrogen atom, -CH= or -CR7= (wherein R7 represents a lower alkyl group, a halogen atom, or a cyano group), with the proviso that at least one of X, Y and Z represent a nitrogen atom, and W represents a nitrogen atom or -CR8= (wherein R8 represents a hydrogen atom, a halogen atom, or a lower alkyl group), and with the proviso that when R1 represents a hydrogen atom, R2 represents an amino group, R3 and R4 represent a fluorine atom, R6 represents a hydrogen atom, X represents a nitrogen atom, Y represents -CR7= (wherein R7 represents a fluorine atom), Z represents -CH=, and W is -CR8= (wherein R8 represents a chlorine atom), then R5 is not a 3-hydroxyazetidine-l-yl group; or a pharmaceutically acceptable salt, ester, or prodrug thereof; with the proviso that R1, R2, R3, R4, R5, R6, R7, R8, W, X, Y, and Z are defined with respect to this claim 18 and any such claims on which this claim 18 depends, or a pharmaceutically acceptable salt, ester, or prodrug thereof. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said quinolone carboxylic compound corresponds to the following structure

or a pharmaceutically acceptable salt, ester, or prodrug thereof. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said quinolone carboxylic acid compound is D-glucitol, l-deoxy-l-(methylamino)-, l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l- azetidinyl)-4-oxo-3-quinolinecarboxylate (salt). In other embodiments, the present invention relates to a pharmaceutical composition, wherein said quinolone carboxylic acid compound is crystalline D-glucitol, 1-deoxy-l- (methylamino)-, l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3- hydroxy-l-azetidinyl)-4-oxo-3-quinolinecarboxylate (salt) characterized, when measured about 25 0C with Cu-Ka radiation, by the powder diffraction pattern shown in FIGURE 1. In other embodiments, the present invention relates to a pharmaceutical composition wherein said quinolone carboxylic acid compound is crystalline D-glucitol, 1-deoxy-l- (methylamino)-, l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3- hydroxy-l-azetidinyl)-4-oxo-3-quinolinecarboxylate (salt) characterized, in the monoclinic crystal system and P 21/C or P21/M space group, when measured by Mo-Ka radiation at about 25°C, by respective lattice parameters a, b, and c of about 16.44460A, 21.4010A, and 5.3050A and β of about 109°. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said quinolone carboxylic acid compound is D-glucitol, l-deoxy-l-(methylamino)-, l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l- azetidinyl)-4-oxo-3-quinolinecarboxylate trihydrate (salt). In other embodiments, the present invention relates to a pharmaceutical composition, wherein said quinolone carboxylic acid compound is crystalline D-glucitol, 1-deoxy-, 1- (methylamino)-l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3- hydroxy-l-azetidinyl)-4-oxo-3-quinolinecarboxylate trihydrate (salt) characterized, when measured about 25 0C with Cu-Ka radiation, by the powder diffraction pattern shown in FIGURE 2. In other embodiments, the present invention relates to a pharmaceutical composition wherein said quinolone carboxylic acid compound is crystalline D-glucitol, 1-deoxy-, 1- (methylamino)-l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3- hydroxy-l-azetidinyl)-4-oxo-3-quinolinecarboxylate trihydrate (salt) characterized, in the monoclinic crystal system and P 21/C or P21/M space group, when measured with Mo- Ka radiation at about 25 0C, by respective lattice parameters a, b, and c of about 8.2490A, 29.9840A and 12.5070A and β of about 105°. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said basifier is selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, and potassium bicarbonate,ethylene diamine, ethylene triamine, ethanolamine, diethanolamine, triethanolamine, arginine, lysine, meglumine, and mixtures thereof. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said basifier is arginine. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said crystallization inhibitior is selected from the group consisting of polyethylene glycol, polymers of l-ethenyl-2-pyrrolidinone; polyamine N-oxide polymers; copolymers of N-vinylpyrrolidone and N-vinylimidazole; polyvinyloxazolidones and polyvinylimidazoles, mixtures thereof. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said crystallization inhibitor is a homopolymer of l-ethenyl-2-pyrrolidinone, especially the homopolymer, particularly a homopolymer having a molecular weight range of about 2500 to 3,000,000 amu. In other embodiments, the present invention relates to a pharmaceutical composition, wherein said crystallization inhibitor is polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b)from about 120 mg to about 600 mg of vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b)from about 120 mg to about 600 mg of vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c)from about 25 mg to about 500 mg of arginine. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c)from about 25 mg to about 500 mg of arginine. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 5 mg to about 100 mg of polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 5 mg to about 100 mg of polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 25 mg to about 500 mg of arginine, and (d) from about 5 mg to about 100 mg of polyvinylpyrrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 25 mg to about 500 mg of arginine, and (d) from about 5 mg to about 100 mg of polyvinylpyrrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) about 240 mg of vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) about 240 mg of vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg of vitamin E TPGS, and (c) about 50mg of arginine. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg of vitamin E TPGS, and (c) about 50mg of arginine. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg of vitamin E TPGS, and (c) about 20 mg of polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg of vitamin E TPGS, and (c) about 20 mg of polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg to about 600 mg of vitamin E TPGS, and (c) about 5 mg to about 500 mg of arginine, and (d) about 20 mg of polyvinylpyrrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg to about 600 mg of vitamin E TPGS, and (c) about 5 mg to about 500 mg of arginine, and (d) about 20 mg of polyvinylpyrrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) about 360 mg of vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) about 360 mg of vitamin E TPGS. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg of vitamin E TPGS, and (c) about 75 mg of arginine. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg of vitamin E TPGS, and (c) about 75 mg of arginine. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg of vitamin E TPGS, and (c) about 30 mg of polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg of vitamin E TPGS, and (c) about 30 mg of polyvinylpyrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition which prior to mixing comprises (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b)about 360 mg to about 600 mg of vitamin E TPGS, and (c) about 5 mg to about 500 mg of arginine, and (d) about 30 mg of polyvinylpyrrolidone K30. In other embodiments, the present invention relates to a pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b)about 360 mg to about 600 mg of vitamin E TPGS, and (c) about 5 mg to about 500 mg of arginine, and (d) about 30 mg of polyvinylpyrrolidone K30. In other embodiments, the present invention relates to a composition for oral administration. In one embodiment, the present invention relates to a method for treating, preventing, or reducing the risk of a bacterial infection comprising administering to a patient in need thereof a composition according to any of the foregoing. In other embodiments, the present invention relates to a method for treating, preventing, or reducing the risk of a bacterial infection comprising administering to a patient in need thereof a composition according to any of the foregoing. In other embodiments, the present invention relates to the manufacture of a medicament for treating, preventing or reducing the risk of a bacterial infection in a patient in need thereof. In other embodiments, the present invention relates to a method for treating, preventing, or reducing the risk of a bacterial infection in a patient in need thereof or to the manufacture of a medicament for treating, preventing or reducing the risk of a bacterial infection in a patient in need thereof, wherein the infection includes, e.g., a skin infection, e.g. complicated skin and skin structure infections (also known as "cSSSI"), uncomplicated skin and skin structure infections (also known as "uSSSI"), acute bacterial skin and skin structure infections "ABSSI"; nosocomial, i.e. hospital-acquired, pneumonia (also known as "HAP"); community acquired pneumonia (also known as "CAP"); post-viral pneumonia; an abdominal infection; a urinary tract infection; bacteremia; septicemia; endocarditis; an atrio-ventricular shunt infection; a vascular access infection; meningitis; infection due to surgical or invasive medical procedures; surgical prophylaxis; a peritoneal infection; a bone infection; a joint infection; a methicillin-resistant Staphylococcus aureus infection; a vancomycin-resistant Enterococci infection; a linezolid-resistant organism infection; a gonorrhoeae infection, e.g. infections caused by Neisseria gonorrhoeae microorganisms; and tuberculosis, e.g. infections caused by Micobacterium tubercoulosis microorganisms. In other embodiments, the present invention relates to a method for treating, preventing, or reducing the risk of a bacterial infection in a patient in need thereof or to the manufacture of a medicament for treating, preventing or reducing the risk of a bacterial infection in a patient in need thereof, wherein the infection includes those caused by Neisseria gonorrhoeae.

1. Definitions The term "patient", as used herein, means the human or animal (in the case of an animal, more typically a mammal) subject. The patient is usually one that is in need of the compositions or methods described herein. The term "preventing", as used herein, means e.g., to completely or almost completely stop an infection from occurring, for example when the patient is predisposed to an infection or at risk of contracting an infection. The term "reducing the risk of, as used herein means, e.g. to lower the likelihood or probability of an infection occurring, for example when the patient is predisposed to an infection or at risk of contracting an infection. The term "treating" as used herein means, e.g. to cure, inhibit, arrest the development of, relieve the symptoms or effects of, ameliorate, or cause the regression of an infection in a patient having an infection. It should be recognized that the terms "preventing", "reducing the risk of, and "treating" are not intended to limit the scope of the invention and that there can be overlap amongst these terms. As used herein, the term "effective amount" means an amount of a pharmaceutically active compound, i.e. a drug active, such as a quinolone carboxylic acid compound given to a recipient patient sufficient to elicit biological activity, for example, anti-infective activity, such as e.g., anti-microbial activity. The term "prophylactically effective amount" means an amount of a pharmaceutically active compound, i.e. a drug active, such as a quinolone carboxylic acid compound given to a recipient patient sufficient to prevent or reduce the risk of a microbial infection. As used herein, the phrase "pharmaceutically acceptable" refers to those compounds, materials, compositions, carriers, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. As used herein, "pharmaceutically acceptable salts" refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. In the case of the quinolone carboxylic acid, the parent compound generally has a carboxylic acid function which can be reacted with an appropriate basic compound to form the salt. Generally, such salts can be prepared by reacting the free acid with a stoichiometric amount of the appropriate base in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990). For example, salts can include, but are not limited to, the ammonium salt, the tetramethylammonium salt, the diethanolammonium salt, and the meglumine salt. Additionally, the compounds of the present invention, for example, the salts of the compounds, can exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules. Nonlimiting examples of hydrates include monohydrates, dihydrates, trihydrates, etc. Nonlimiting examples of solvates include ethanol solvates, acetone solvates, etc. As used herein, "pharmaceutically acceptable esters" refer to derivatives of the disclosed compounds wherein the parent compound is esterified, i.e. a carboxylic acid functional group is modified with an alcohol to form an ester, or an alcohol functional group is modified with a carboxylic acid to form an ester. As used herein, "pharmaceutically acceptable prodrugs" refer to derivatives, including ester of the parent compound wherein the parent compound is converted into some other chemical form for delivery. Generally, a prodrug is an inactive or less active or masked form of the pharmaceutical active. As used herein, "prior to mixing", refers to the components of the compositions of the present invention before they are combined. In the specification, the singular forms also include the plural, unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the case of conflict, the present specification will control. All percentages and ratios used herein, unless otherwise indicated, are by weight. Throughout the description, where compositions are described as having, including, or comprising specific components, it is contemplated that compositions also consist essentially of, or consist of, the recited components. Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps or order for performing certain actions is immaterial so long as the invention remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

2. Compositions of the present invention The compositions of the present invention comprise the following essential and optional components. The compositions can be defined either prior to or after mixing of the components. Suitable components are described in e.g., Eds. R. C. Rowe, et al, Handbook of Pharmaceutical Excipients, Fifth Edition, Pharmaceutical Press (2006); Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990); and Remington: The Science and Practice of Pharmacy, 20th Edition, Baltimore, MD: Lippincott Williams & Wilkins, 2000, which are incorporated by reference herein in their entirety. Even though a functional category can be provided for many of these carrier components, such a functional category is not intended to limit the function or scope of the component, as one of ordinary skill in the art will recognize that a component can belong to more than one functional category and that the level of a specific component and the presence of other components can effect the functional properties of a component. a. Quinolone Carboxylic Acid Compound The compositions of the present invent comprise a quinolone carboxylic acid compound, or a pharmaceutically acceptable salt, ester, or prodrug thereof, as an antimicrobial compound, i.e. as the pharmaceutical drug active of the compounds of the present invention. The quinolone carboxylic acid compound is alternatively known as a pyridone carboxylic acid or a pyridone carboxylic acid derivative. The invention further provides methods for synthesizing any one of the compounds of the present invention. The invention also provides pharmaceutical compositions comprising an effective amount of one or more of the compounds of the present invention and a pharmaceutically acceptable carrier. The present invention further provides methods for making these compounds, carriers, and pharmaceutical compositions. As used herein the term "quinolone carboxylic acid compounds" includes quinolone carboxylic acid compounds, useful herein which are described, including their synthesis, formulation, and use, in U.S. Patent No. 6,156,903, to Yazaki et al., issued December 5, 2000 and its certificates of correction of November 13, 2001 and December 11, 2001; U.S. Patent No. 6,133, 284, to Yazaki et al., issued October 17, 2000; U.S. Patent No. 5,998, 436, to Yazaki et al., issued December 7, 1999 and its certificates of correction of January 23, 2001, October 30, 2001, and December 17, 2002; PCT Application No. WO 2006/1 10815, to Abbott Laboratories, published October 19, 2006; PCT Application No. WO 2006/042034, to Abbott Laboratories, published April 20, 2006, PCT Application No. WO 2006/015 194, to Abbott Laboratories, published February 9, 2006; PCT Application No. WO 01/34595, to Wakunaga Pharmaceutical Co., Ltd., published May 17, 2001; and PCT Application No. WO 97/1 1068, to Wakunaga Pharmaceutical Co., Ltd., published March 27, 1997; the foregoing all of which are incorporated by reference herein in their entirety. Quinolone carboxylic acid compounds of the present invention include compounds corresponding to the following structure (Quinolone Carboxylic Acid Compound 1)

Quinolone Carboxylic Acid Compound 1, wherein with respect to Quinolone Carboxylic Acid Compound 1, R1 represents a hydrogen atom or a carboxyl protective group; R2 represents a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; R3 represents a hydrogen atom or a halogen atom; R4 represents a hydrogen atom or a halogen atom; R5 represents a halogen atom or an optionally substituted saturated cyclic amino group; R6 represents a hydrogen atom, a halogen atom, a nitro group, or an optionally protected amino group; X, Y and Z may be the same or different and respectively represent a nitrogen atom, -CH= or -CR7= (wherein R7 represents a lower alkyl group, a halogen atom, or a cyano group), with the proviso that at least one of X, Y and Z represent a nitrogen atom, and W represents a nitrogen atom or -CR8= (wherein R8 represents a hydrogen atom, a halogen atom, or a lower alkyl group), and with the proviso that when R1 represents a hydrogen atom, R2 represents an amino group, R3 and R4 represent a fluorine atom, R6 represents a hydrogen atom, X represents a nitrogen atom, Y represents - CR7= (wherein R7 represents a fluorine atom), Z represents -CH=, and W is -CR8= (wherein R8 represents a chlorine atom), then R5 is not a 3-hydroxyazetidine-l-yl group; or a pharmaceutically acceptable salt, ester, or prodrug thereof. As described in the foregoing paragraph, when R1 is a carboxyl protective group, it may be any carboxylate ester residue which cleaves relatively easily to generate the corresponding free carboxyl group. Exemplary carboxyl protective groups include those which may be eliminated by hydrolysis, catalytic reduction, and other treatments under mild conditions such as lower alkyl groups such as methyl group, ethyl group, n-propyl group, i- propyl group, n-butyl group, i-butyl group, t-butyl group, pentyl group, hexyl group, and heptyl group; lower alkenyl groups such as vinyl group, allyl group, 1-propenyl group, butenyl group, pentenyl group, hexenyl group, and heptenyl group; aralkyl groups such as benzyl group; and aryl groups such as phenyl group and naphthyl group; and those which may be readily eliminated in the body such as lower alkanoyloxy lower alkyl groups such as acetoxymethyl group and pivaloyloxymethyl group; lower alkoxycarbonyloxy lower alkyl group such as methoxycarbonyloxymethyl group and 1-ethoxycarbonyloxyethyl group; lower alkoxymethyl group such as methoxymethyl group; lactonyl group such as phthalidyl; di- lower alkylamino lower alkyl group such as 1-dimethylaminoethyl group; and (5-methyl-2- oxo- 1,3-dioxole-4-yl)methyl group. In other embodiments, the present invention relates to a method, composition, or use for a quinolone carboxylic acid compound of structure Quinolone Carboxylic Acid Compound 1, wherein W is -CR8=, wherein R8 represents a hydrogen atom, a halogen atom, or a lower alkyl group. In other embodiments, the present invention relates to a method, composition, or use for a quinolone carboxylic acid derivative of structure Quinolone Carboxylic Acid Compound

1, wherein R5 is a cyclic amino group represented by the following formula (a) or (b): (a)

(CH 2 )e N

(b)

wherein A represents an oxygen atom, sulfur atom or NR9 (wherein R9 represents hydrogen atom or a lower alkyl group), e represents a number from 3, 4 or 5, f represents a number from 1, 2, or 3, g represents a number from 0, 1, or 2, J1, J2 and J3, which may be the same or different from one another, represent a hydrogen atom, hydroxyl group, lower alkyl group, amino lower alkyl group, amino group, lower alkylamino group, lower alkoxy group, or a halogen atom. In other embodiments, the present invention relates to a method, composition, or use for a quinolone carboxylic acid compound of structure Quinolone Carboxylic Acid

Compound 1, wherein R5 is a cyclic amino group represented by formula (a) (a)

(CH 2 )e N In other embodiments, the present invention relates to a method, composition, or use for a quinolone carboxylic acid compound of structure Quinolone Carboxylic Acid

Compound 1, wherein e in the formula (a) is 3 or 4.

In other embodiments, the present invention relates to a method, composition, or use for a quinolone carboxylic acid derivative of structure Quinolone Carboxylic Acid Compound

1, wherein R1 is a hydrogen atom; R2 is an amino group, lower alkylamino group, or a di- lower alkylamino group; R3 is a halogen atom; R4 is a halogen atom; R6 is hydrogen atom; X is a nitrogen atom; Y and Z are -CH= or -CR7= (wherein R7 is a lower alkyl group or a halogen atom); and W is -CR8= (wherein R8 is a halogen atom or a lower alkyl group). In other embodiments, the present invention relates to a method, composition, or use for a quinolone carboxylic acid derivative of structure Quinolone Carboxylic Acid Compound

1, wherein R2 is amino group; R3 is fluorine atom; R4 is a fluorine atom; Y is -CF=; Z is - CH=; W is -CR8= (wherein R8 is a chlorine atom, bromine atom or a methyl group), and e in formula (a) is 3. (a)

(CH 2 )e N

It is noted that the substituents R1, R2, R3, R4, R5, R6, R7, R8, R9, A, J1, J2, J3, W, X, Y, Z, e, f , and g are defined herein for convenience with respect to the chemical structure for the quinolone carboxylic acid compounds. In other embodiments, the present invention relates to a method, composition, or use wherein said quinolone carboxylic acid compound corresponds to the following structure: or a pharmaceutically acceptable salt, ester, or prodrug thereof. This foregoing quinolone carboxylic acid is also known by the names USAN, delafloxacin, the publicly disclosed code names RX-3341, ABT-492 and WQ 3034, and also by, inter alia, the chemical name l-(6- amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l-azetidinyl)-4- oxo-3-quinolinecarboxylic acid or l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro- l,4-dihydro-7-(3-hydroxyazetidin-l-yl)-4-oxo-3-quinolinecarboxylic acid. This carboxylic acid form of the compound corresponds to the CAS Registry Number 189279-58-1. Furthermore, WO 2006/042034, cited above discloses the 1-deoxy- l-(methylamino)-D- glucitol salt of this compound, [D-glucitol, 1-deoxy- 1-(methylamino)- 1-(6-amino-3 ,5- difluoro-2-pyridinyl)-8-chloro-6-fluoro- 1,4-dihydro-7-(3-hydroxy- 1-azetidinyl)-4-oxo-3- quinolinecarboxylate (salt)] and the trihydrate of the 1-deoxy- l-(methylamino)-D-glucitol salt of this compound, [D-glucitol, 1-deoxy- 1-(methylamino)- l-(6-amino-3, 5-difluoro-2- pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l-azetidinyl)-4-oxo-3- quinolinecarboxylate trihydrate (salt)]. The 1-deoxy-l-(methylamino)-D-glucitol salt and the 1-deoxy- l-(methylamino)-D-glucitol salt trihydrate correspond to the CAS Registry Numbers 352458-37-8 and 883105-02-0, respectively. 1-deoxy- l-(methylamino)-D-glucitol corresponds to the CAS Registry Number 6284-40-8. 1-deoxy- l-(methylamino)-D-glucitol is also known by the name meglumine. D-glucitol, 1-deoxy-1-(methylamino)-, l-(6-amino-3,5- difluoro-2-pyridinyl)-8-chloro-6-fluoro- 1,4-dihydro-7-(3-hydroxy- 1-azetidinyl)-4-oxo-3- quinolinecarboxylate is also know as delafloxacin meglumine. D-glucitol, 1-deoxy- 1- (methylamino)-, l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3- hydroxy-l-azetidinyl)-4-oxo-3 -quinolinecarboxylate trihydrate is also known as delafloxacin meglumine trihydrate. WO 2006/042034 also discloses a crystalline form of the 1-deoxy-l- (methylamino)-D-glucitol salt characterized when measured at about 25 0C with Cu-Ka radiation, by the powder diffraction pattern shown in FIGURE 1 (see WO 2006/042034) and a crystalline form of the l-deoxy-l-(methylamino)-D-glucitol salt trihydrate when measured at about 25 0C with Cu-Ka radiation, by the powder diffraction pattern shown in FIGURE 2 (see WO 2006/042034). These l-deoxy-l-(methylamino)-D-glucitol salts are useful in the present invention. Also, see A.R. Haight et al., "Synthesis of the Quinolone ABT-492: Crystallizations for Optimal Processing", Organic Process Research & Development (2006), 10(4), 751-756. Additionally other pharmaceutically acceptable salts of the forgoing compound, delafloxacin, include the potassium salt and the tris salt. Tris is a common abbreviation for tris(hydroxymethyl)aminomethane, which is known by the IUPAC name 2-Amino-2- hydroxymethyl-propane- 1,3-diol. The quinolone carboxylic acid compound comprises from about 0.01% to about 99% by weight of the composition. In further embodiments, the quinolone carboxylic acid compound comprises from about 1% to about 90% by weight of the composition. In yet further embodiments, the quinolone carboxylic acid compound comprises from about 5% to about 80% by weight of the composition. In yet further embodiments, the quinolone carboxylic acid compound comprises from about 10% to about 70% by weight of the composition. In yet further embodiments, the quinolone carboxylic acid compound comprises from about 20% to about 60% by weight of the composition. Examples of further dosages are given below. The weight percentage of the quinolone carboxylic acid compound is determined on an active weight basis of the parent compound. In other words, appropriate adjustments and calculations well known to one of ordinary skill in the art can be readily performed to determine the active weight basis. As a nonlimiting example, if the parent free carboxylic acid of delafloxacin, i.e. l-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro- 7-(3-hydroxy- l-azetidinyl)-4-oxo-3-quinolinecarboxylic acid, is used, its weight would have to be adjusted if a salt such as the sodium salt were to be used, because the molecular weight of the salt would increase by about 21.9 amu, although the amount of active compound delivered by administering the salt is the same. The dose of the pharmaceutical active and mode of administration of the pharmaceutical composition will depend upon the intended patient or subject and the targeted microorganism, e.g., the target bacterial organism. As further described below, it is often advantageous to mill the pharmaceutical active to a small and uniform particle size, usually in the micron range, i.e. micronization. Milling can be performed using standard techniques well known to one of ordinary skill in the art. Useful particle size ranges for the pharmaceutical active are generally from about 0.01 microns to about 200 microns, preferably from about 0.1 microns to about 100 microns, and even more preferably from about 2 microns to about 50 microns. b. Absorption Enhancer The compositions of the present include an absorption enhancer. Examples of absorption enhancers include alkyl glycosides, polysorbates, polyglycolized glycerides, and alkoxylated tocopheryl esters. Alkyl glycosides include for example dodecylmaltoside. Polysorbates, which are PEG-olated sorbitans esterified with fatty acids, include Polysorbate 80. Polyglycolized glycerides are also known as polyglycolysed glycerides. These materials are generally surface active and depending on their exact composition have a range of melting points and hydrophilic/lipophilic balance ranges (HLBs). These materials are often further combined with a polyhydric alcohol, such as glycerol. The polyglycolized glycerides are mixtures of glycerides of fatty acids and of esters of polyoxy ethylene with fatty acids. In these mixtures, the fatty acids are generally saturated or unsaturated C -C22, for example C8 -Ci 2 or Ci6 -C20. The glycerides are generally monoglycerides, diglycerides, or triglycerides or mixtures thereof in any proportions. Polyglycolysed glycerides are marketed e.g., by Gattefosse under the trade names Labrafϊ l, Labrosol, and Gelucire. The Gelucire polyglycolized glycerides are often designated with the melting point and HLB. For example, Gelucire 53/10 refers to a material having a melting point of 53 0C and an HLB of 10. Gelucire materials useful herein include Gelucire 44/14 and Gelucire 50/13. Alkoxylated tocopheryl esters are alkoxylated ester derivatives of tocopherol. In some embodiments the alkoxylated tocopheryl ester is an alkoxylated tocopheryl monoester of a dicarboyxlic acid. In yet further embodiments, the alkoxylated tocopheryl ester is an alkoxylated tocopheryl monosuccinicate. In yet further embodiments the alkoxylated tocopheryl ester is an ethoxylated tocopheryl monosuccinate. Tocopherol is a class of compounds having vitamin E activity. Examples of tocopherols include alpha-tocopherol, dl-alpha-tocopherol, beta-tocopherol, gamma- tocopherol, and delta-tocopherol. The free hydroxy group of tocopherol, which is a phenolic group, can be used to form an ester with carboxylic acids. If a dicarboxylic acid is used to form a monoester with tocopherol, the remaining carboxylic acid group of the dicarboyxlic acid can be used to form an ester with a polyalkylene glycol such as polyethylene glycol, polypropylene glycol, or the like. An alkoxylated tocopheryl ester useful herein is vitamin E tocopheryl polyethylene glycol succinate. This material is also known as vitamin E TPGS, TPGS, and tocophersolan and corresponds to the Chemical Abstracts Services ("CAS") Registry Number 9002-96-4. The following information for vitamin E TPGS is from the publicly available information for CAS Registry Number 9002-96-4. Registry Number: 9002-96-4

PAGE 1 - A

r ' I HO CH 2 — CH 2 O C— CH 2— CH 2 ~

PAGE 1 - B

Me Me I I CH- (CH 2 ) 3 — CH- (CH 2 ) 3 CHMe 2

Formula: (C2H4O)UC33H54O5 CA Index Name: Poly(oxy-1, 2-ethanediyl), α-[4-[[(2R)-3,4-dihydro-2,5,7,8- tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-2H-l-benzopyran- 6-yl]oxy]-l,4-dioxobutyl]- ω-hydroxy- Other Names: Poly(oxy-l,2-ethanediyl), α-[4-[[3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl)-2H-l-benzopyran-6-yl]oxy]-l,4- dioxobutyl]- ω-hydroxy-, [2R-[2R*(4R*,8R*)]]-; D IT; D-α- Tocopherol polyethylene glycol 1000 succinate; D-α-Tocopheryl polyethylene glycol succinate; Eastman Vitamin ETPGS; Mono[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-6-chromanyl] succinate, polyoxyethylene ether; TPGS; Tocofersolan; Tocophersolan (this is the USAN); VE-TPGS 1000; VitE-TPGS; Vitamin E-TPGS; d-α-Tocopheryl poly(ethylene glycol) 1000 succinate; d-α-Tocopheryl polyethylene glycol succinate; α- Tocopherol polyethylene glycol succinate; α-Tocopheryl polyethylene glycol succinate Class Identifier: Polymer Polymer Class Term: Polyether

It should be recognized that vitamin E TPGS, because it is a polymeric material, will correspond to a mixture of compounds. The commercially available material generally contains polyethylene glycol 1000 and corresponds to a total molecular weight of approximately 1513 amu. c. Basifier The compositions of the present invention can further comprise various materials for modifying or adjusting the pH of the composition. Such materials include bases and buffering systems, etc. Nonlimiting examples of basifier include, for example sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, and potassium bicarbonate. Further examples of basifϊ ers include ethylene diamine, ethylene triamine, ethanolamine, diethanolamine, and triethanolamine. Yet further examples of basifϊ ers include basic amino acids, examples of which include arginine and lysine. Other examples of basifϊ ers include polyhydroxy amine compounds, such as described elsewhere herein. More specifically, the polyhydroxy amine compound, meglumine, can be used as a basifier. For solid oral compositions such as tablets or capsules, the compositions should be formulated to provide a buffering capacity of a pH of about 8. For aqueous compositions of the present invention, the aqueous composition should have a pH so that the composition is suitable for administration to a patient or subject. The compositions have a pH from about pH 7 to about pH 11. In further embodiments, the compositions have a pH from about pH 8.5 to about pH 10. In further embodiments, the compositions have a pH from about pH 9 to about pH 9.5. In further embodiments, the compositions have a pH from about pH 9.2 to about pH 9.4. d. Crystallization Inhibitor The compositions of the present invention comprise a crystallization inhibitor. Such crystallization inhibitors inlcude polyethylene glycol, polymers of l-ethenyl-2-pyrrolidinone; polyamine N-oxide polymers; copolymers of N-vinylpyrrolidone and N-vinylimidazole; polyvinyloxazolidones and polyvinylimidazoles or mixtures thereof. Particularly useful are polymers of l-ethenyl-2-pyrrolidinone, especially the homopolymer. Generally this homopolymer has a molecular weight range of about 2500 to 3,000,000 amu. This homopolymer is known as polyvinylpyrolidone, PVP, or povidone. A particular example of such a crystallization inhibitor is polyvinylpyrolidone K30, which can be utilized as a solution. Examples of other crystallization inhibitors include cellulose derivatives such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose (HPMC), hydroxypropylmethyl celluose acetylsuccinate (HMPCAS), hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, and sodium carboxy-methyl cellulose; alginic acid derivatives; polyvinylpyrrolidone; . The crystallization inhibitor can comprise from about 0.1% to about 99.9% of the compositions of the present invention. In other embodiments, the polymeric dissolution aid can comprise from about 1% to about 10%, from about 1% to about 5%, and from about 2.5% to about 3.5% of the compositions of the present invention. e. Other Ingredients The compositions of the present invention can further comprise one or more additional components selected from a wide variety of excipients known in the pharmaceutical formulation art. According to the desired properties of the tablet or capsule, any number of ingredients can be selected, alone or in combination, based upon their known uses in preparing the compositions of the present invention. Such ingredients include, but are not limited to solvents (e.g. ethanol); colorants; waxes, gelatin; preservatives (e.g., methyl paraben, sodium benzoate, and potassium benzoate); antioxidants [e.g., butylated hydroxyanisole ("BHA"), butylated hydroxytoluene ("BHT"), and vitamin E and vitamin E esters such as tocopheryl acetate]; surfactants; buffers; stabilizers; chelators; UV-absorbers, etc. i. Fillers The compositions of the present invention can further comprise a filler. Examples of fillers are microcrystalline cellulose; glucose; lactose; mannose; dextrose; mannitol; sorbitol; sucrose; starches; fumed silica; salts such as sodium carbonate and calcium carbonate; polyols such as propylene glycol; and starches such as ordinary starch and sodium starch succinate. Other examples of starches include corn starch and potato starch; gelatin; and tragacanth. The fillers are present in an amount of from 0% to about 50% by weight of the composition, either alone or in combination. In other embodiments they are present from about 5% to about 20% of the weight of the composition. ii. Water The compositions of the present invention can further comprise water. In these further embodiments, the compositions comprise from 0% to about 99.9% water, in further embodiments from about 1% to about 99% water, in yet further embodiments from about 5% to about 95% water, and in yet further embodiments from about 10% to about 90% water. In defining a composition, the amount of water can be designated as "q.s." or "Q.S.", which means or designates as much as suffices, to provide a final composition or volume of 100%. iii. Sugars and Sugar Alcohols The compositions of the present invention, especially when further made into a lyophile, can further comprise a sugar, a sugar alcohol, or mixtures thereof. Without being limited by theory, these sugars and sugar alcohols are believed to aid in the formation of the lyophile during the lyophilization process. Typically, the lyophile is made by drying the composition under appropriate conditions, such as, for example, by freeze drying. Nonlimiting examples of sugars include mannose, sucrose, dextrose, and mixtures thereof. Nonlimiting examples of sugar alcohols useful herein include mannitol and xylitol and mixtures thereof. The compositions comprise from about 0% to about 50% of a sugar or sugar alcohol. iv. Polyhydroxy Amine Compound The compositions of the present invention can comprise a polyhydroxy amine compound. The polyhydroxy amine compound described herein can encompass the meglumine salt described above for the quinolone carboxylic acid, delafloxacin, and also which is further described under the section of basifiers. The polyhydroxy amine compound is generally a C3, C , C5, C , C7, or C straight, branched, or cyclic compound having 2 or more hydroxy substituents, and at least one amine (either substituted or unsubstituted) substituent. In further embodiments the polyhydroxy amine compound is meglumine. Meglumine corresponds to CAS Registry Number 6284-40-8 and is also known as meglumine, USP; 1- Deoxy-l-(methylamino)-D-glucitol; N-Methyl-D-glucamine; Glucitol, 1-deoxy- 1- (methylamino)-, D- (8Cl); Sorbitol, 1-deoxy-l-methylamino- (6Cl); 1-Deoxy- 1- (methylamino)-D-glucitol; 1-Deoxy- 1-methylaminosorbitol; D-(-)-N-Methylglucamine; Meglumin; Methylglucamin; Methylglucamine; N-Methyl-D(-)-glucamine; N-Methyl-D- glucamine; N-Methylglucamine; N-Methylsorbitylamine; NSC 52907; NSC 7391. It also has the CA Index Name D-Glucitol, 1-deoxy-l-(methylamino)- (9Cl). A chemical formula for meglumine is as follows: OH OH

The polyhydroxy amine compound comprises from 0% to about 50% by weight of the composition. In further embodiments, the polyhydroxy amine compound comprises from about 0.25% to about 20% by weight of the composition. In yet further embodiments, the polyhydroxy amine compound comprises from about 0.5% to about 10% by weight of the composition. In yet further embodiments, the polyhydroxy amine compound comprises from about 1% to about 5% by weight of the composition. It is to be noted that the specific exemplification of the polyhydroxy amine compound described here is not intended to limit the use of this compound in the present invention where it can also be employed to form a salt of the quinolone carboxylic acid pharmaceutical active, as described further above and where it can also be used as a basifϊ er. In other words, for example, the description of meglumine here, and its use as a formulation excipient, does not preclude its use also for preparing a meglumine salt of the quinolone carboxylic acid pharmaceutical active and also its use as a basifϊ er. v. Cyclodextrins When the composition is in the form of an aqueous solution, particularly an intravenous formulation, the composition can further comprise a cyclodextrin. Cyclodextrins useful herein are known in the literature or are commercially available. The compositions of the present invention include cyclodextrins selected from the group consisting of alpha- cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, alkylcyclodextrins (e.g., methyl-beta- cyclodextrin, dimethyl-beta-cyclodextrin, diethyl-beta-cyclodextrin), hydroxyalkylcyclodextrins (e.g., hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta- cyclodextrin), carboxyalkylcyclodextrins (e.g., carboxymethyl-beta-cyclodextrin), and sulfoalkylether cyclodextrins (e.g., sulfobutylether-beta-cyclodextrin). The cyclodextrin is used in a weight percentage in the composition to provide the desired pharmacological properties, such as e.g. drug bioavailability from the final composition. Weight percentages of the cyclodextrin range from 0% to about 99%, from about 10% to about 90%, from about 20% to about 80%, from about 30% to about 70%, and from about 40% to about 60%.

3. Processing The compositions of the present invention are made using convention equipment and mixing techniques. The compositions can also be made in the form of a lyophile, i.e. a freeze-dried composition, particularly for compositions to be administered intravenously. The lyophile is reconstituted with water or an aqueous solution prior to administration. Lyophilization, also known as freeze-drying is a dehydration process to remove the liquid, typically water and other relatively volatile solvents, from a material. Freeze drying works by freezing the material and then reducing the surrounding pressure and, as appropriate, adding enough heat to allow the frozen water and other solvents in the material to sublime directly from the solid phase to gas.

4. Packaging The compositions of the present invention, when in the form of solids for oral administration can be in the form of tablets or capsules. The tablets can be made by compression and the capsules can be made by filing standard gelatin capsules. The tablets and capsules can be packaged in jars, vials, blister packs, etc. The compositions of the present invention, when in the form of solutions, can be packaged in standard, commercially available containers such as vials. Generally, the vial is glass. The glass can be colorless or colored, clear or amber. Various types of closure systems can be used such as screw vials (closed with screw cap), lip vials (closed with a stopper), or crimp vials (closed with a rubber stopper and a metal cap). Additionally, the compositions of the present invention, including a reconstituted loophole, can be further diluted into an intravenous delivery bag or bottle. Furthermore, the compositions of the present invention, when in the form of liquids can be packaged for ocular, otic, or nasal delivery. 5. Doses and Methods of Treating, Preventing, or Reducing the Risk of Infections The compositions of the present invention are useful for treating, preventing or reducing the risk of infection. Such nonlimiting examples of infections include, e.g., a skin infection, e.g. complicated skin and skin structure infections (also known as "cSSSI"), uncomplicated skin and skin structure infections (also known as "uSSSI"), acute bacterial skin and skin structure infections "ABSSSI"; nosocomial, i.e. hospital-acquired, pneumonia (also known as "HAP"); community acquired pneumonia (also known as "CAP"); post-viral pneumonia; an abdominal infection; a urinary tract infection; bacteremia; septicemia; endocarditis; an atrio-ventricular shunt infection; a vascular access infection; meningitis; infection due to surgical or invasive medical procedures; surgical prophylaxis; a peritoneal infection; a bone infection; ajoint infection; a methicillin-resistant Staphylococcus aureus infection; a vancomycin-resistant Enterococci infection; a linezolid-resistant organism infection; a gonorrhoeae infection, e.g. infections caused by Neisseria gonorrhoeae microorganisms; and tuberculosis, e.g. infections caused by Micobacterium tubercoulosis microorganisms. The term "microbial infection" as used herein is a more general term including bacterial infections, fungal infections, etc. Microbes include bacterial and fungi. The dose of active compound and mode of administration, e.g., oral administration, injection, intravenous drip, ocular administration, otic administration, nasal administration, etc. will depend upon the intended patient or subject and the targeted microorganism, e.g., the target bacterial organism, and the location of the infection in the patient or subject. Compositions can be formulated in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals. Furthermore, administration can be by periodic injections of a bolus, or can be made more continuous by intravenous, intramuscular or intraperitoneal administration from an external reservoir (e.g., an intravenous bag). In conjunction with the methods of the present invention, pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) can be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, a physician or clinician can consider applying knowledge obtained in relevant pharmacogenomics studies in determining whether to administer a drug as well as tailoring the dosage and/or therapeutic regimen of treatment with the drug. Generally, an effective amount of dosage of active compound will be in the range of from about 0.1 to about 100 mg/kg of body weight/day, more preferably from about 1.0 to about 50 mg/kg of body weight/day. The amount administered will also likely depend on such variables as the overall health status of the patient, the relative biological efficacy of the compound delivered, the formulation of the drug, the presence and types of excipients in the formulation, the route of administration, and the infection to be treated, prevented, or reducing the risk of. Also, it is to be understood that the initial dosage administered can be increased beyond the above upper level in order to rapidly achieve the desired blood-level or tissue level, or the initial dosage can be smaller than the optimum. Nonlimiting doses of active compound comprise from about 0.1 to about 1500 mg per dose. Nonlimiting examples of doses, which can be formulated as a unit dose for convenient administration to a patient include: about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, about 500 mg, about 525 mg, about 550 mg, about 575 mg, about 600 mg, about 625 mg, about 650 mg, about 675 mg about 700 mg, about 725 mg, about 750 mg, about 775 mg, about 800 mg, about 825 mg, about 850 mg, about 875 mg, about 900 mg, about 925 mg, about 950 mg, about 975 mg, about 1000 mg, about 1025 mg, about 1050, mg, about 1075 mg, about 1100 mg, about 1125 mg, about 1150 mg, about 1175 mg, about 1200 mg, about 1225 mg, about 1250 mg, about 1275 mg, about 1300 mg, about 1325 mg, about 1350 mg, about 1375 mg, about 1400 mg, about 1425 mg, about 1450 mg, about 1475 mg, and about 1500 mg. The foregoing doses are useful for administering the compounds of the present invention according to the methods of the present invention. The foregoing doses are particularly useful for administering the quinolone carboxylic acid compounds of the present invent, particularly the compound known by the name delafloxacin and pharmaceutically acceptable salts, esters and prodrugs thereof. As is understood by one of ordinary skill in the art, generally, when dosages are described for a pharmaceutical active, the dosage is given on the basis of the parent or active moiety. Therefore, if a salt, hydrate, or another form of the parent or active moiety is used, a corresponding adjustment in the weight of the compound is made, although the dose is still referred to on the basis of the parent or active moiety delivered. As a nonlimiting example, if the parent or active moiety of interest is a monocarboxylic acid having a molecular weight of 250, and if the monosodium salt of the acid is desired to be delivered to be delivered at the same dosage, then an adjustment is made recognizing that the monosodium salt would have a molecular weight of approximately 272 (i.e. minus IH or 1.008 atomic mass units and plus 1 Na or 22.99 atomic mass units). Therefore, a 250 mg dosage of the parent or active compound would correspond to about 272 mg of the monosodium salt, which would also deliver 250 mg of the parent or active compound. Said another way, about 272 mg of the monosodium salt would be equivalent to a 250 mg dosage of the parent or active compound. Using delafloxacin as a nonlimiting example, an example of a composition useful in the methods of the present invention can be about 300 mg of delafloxacin, or a pharmaceutically acceptable salt or ester thereof.

6. Examples The following examples further describe and demonstrate embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention. Ingredients are identified by chemical, USP, or CTFA name. The following formulations are preparing using mixing techniques and equipment familiar to one of ordinary skill in the art. These formulations are useful for treating, preventing, or reducing the risk of a microbial infection in a patient.

Example 1. Formulations for Oral Administration

(a) Delafloxacin Meglumine Active Pharmaceutical Ingredient in 144.3 mg = 100 mg free acid (b) Vitamin E TPGS was melted and incorporated into the formulation as a granulation fluid. (c) Water was removed during drying process.

Alternatively, other formulations can be made by replacing the microcrystalline cellulose with other fillers such as mannitol, lactose, xylitol, or other materials that can be used as fillers at an approximately equivalent or different weight. The manufacturing process involves, but is not limited to as described immediately below. • The vitamin E TPGS was melted with mixing in a 55 0C oven to form a uniform melt and the appropriate amount was then weighed into a granulation beaker and held at 40-55 0C. • The delafloxacin and the intragranular excipient(s), such as for example, arginine, PVP, microcrystalline cellulose, were weighed into a mixing vessel and mixed using a mechanical mixer. • This mixture was then mixed with the melted vitamin E TPGS and granulated to form a uniform granulation. If necessary, water can be added to help the granulation. • The resulting mixture was then dried at 30-35 0C until dried. • The material was then passed through a screen and collected in a mixing vessel. • This material was mixed with the extragranular excipients (such as magnesium stearate) in a mechanical mixer. • The resulting material was compressed into individual tablets, or alternatively loaded into standard gelatin capsules. The resulting formulations are useful for oral administration, for treating, preventing, or reducing the risk of a microbial infection in a patient.

Example 2. Formulations for Oral Administration

Example 4. Comparative Formulations for In Vitro and In Vivo Evaluation Various formulations, described in the Table 4 below, were evaluated for in-vitro dissolution (FIGURE 3 and FIGURE 4) and in-vivo exposure in beagle dogs for oral exposure at 100 mg dose (Table 5). • Formulation I Delafloxacin Active Pharmaceutical Ingredient (API) in capsule as control

• Formulation I Delafloxacin Active Pharmaceutical Ingredient (API) in capsule co administered with Vitamin E TPGS solution • Formulation II • Formulation III with PVP and arginine • Formulation III co-administered with Vitamin E TPGS solution,, • Formulation IV and Formulation V (amorphous formulations)

• Formulation of Example 1.

Table 4.

a. FA=free acid b. Co-administrated as solution

Formualtions II and III were manufactured using standard wet granulation processes. The amorphous Formulations IV and V were produced using standard spray drying processes. Example 5. Oral Exposure Results of Formulations in Dogs The delafloxacin oral formulations studied in beagle Dogs at 100 mg are shown below in Table 5. Exposure describes the amount of the drug in the blood circulation system over a period of time after administration. It is measured by area under curve, i.e the plasma concentration time curve, which is abbreviated as AUC. The time period covered is from zero (time of administration) to 8 hours. Exposure or AUC is a pharmacokinetic parameter known to one of ordinary skill in the art and is useful for comparing the relative bioavailability of different drug products.

Table 5

The exposure results in dogs (Table 5, above) indicated that the combination of Vitamin E TPGS with dissolution enhancers such as PVP and Arginine, such as in Formulation III (co-administered with Vitamin E TPGS) and Example 1, is necessary to increase exposure. The other formulations did not increase exposure in dogs. The examples of these other formulations are presented in Table 4, above. Also, neat delafloxacin API in capsule co-administered with Vitamin E TPGS did not increase exposure in dogs. Example 6. Summary of Oral Formulations The following Table 6 provides a summary of the components useful in the compositions of the present invention.

Table 6.

(a) Can also be co-administered with the dosage form as alternative. (b) The two ingredients in this example are not be 0% at the same time. (c) Removed during process Example 7. Formulation for Oral Administration

Figure 3 shows the 2-step dissolution of delafloxacin megluminecapsules used in Study 1 of Example 5 above. These results show an increase in dissolution for components such as arginine (a basifer) and PVP (which is a crystallization inhibitor). However, this dissolution enhancement did not provide a bioavailability improvement as seen from the dog study of Example 5, above.

Example 8. Formulation for Oral Administration Figure 4 shows the 2-step dissolution profile of delafloxacin meglumine formulations used in Study 2 of Example 5 above. Based on these results, no dissolution enhancements were seen for vitamin E TPGS based on solubility alone. However, an advantage is seen based on bioavailability in the dog study below.

Table 8 Example 9. Formulation for Intravenous Administration

The vitamin E TPGS is melted with mixing in a 55 0C oven to form a uniform melt and the appropriate amount is then weighed into a container held at 40-55 0C. The meglumine and mannitol are added to the water and mixed until dissolved. The melted vitamin E TPGS is added to the water solution with mixing. Next the delafloxacin meglumine is added with further mixing until dissolved. The resulting mixture should have a pH of about 9.0 and can be adjusted as necessary using IN sodium hydroxide or IN hydrochloric acid. The resulting mixture is useful for intravenous administration or alternatively for administration by injection, for treating, preventing, or reducing the risk of a microbial infection in a patient. Formulations can also be prepared as lyophilisates. Such formulations are reconstituted with water or another appropriate aqueous-based solution. These lyophilisates are a compact and convenient form for storing the formulation. Example 10. Formulation for Ocular Administration

*This buffer includes phosphate salts to provide a final amount of 1.24 mg/mL of sodium phosphate monobasic (NaH PO ) and 2.27 mg/mL of sodium phosphate dibasic (Na HPO ) in the finished product. The vitamin E TPGS is melted with mixing in a 55 0C oven to form a uniform melt and the appropriate amount is then weighed into a container held at 40-55 0C. The chlorobutanol and the phosphate buffer is added to the batching water. The melted vitamin E TPGS is added to the water solution with mixing. Next the delafloxacin meglumine is added with further mixing until dissolved. The resulting mixture should have a pH of about 7.0 and can be adjusted as necessary using IN sodium hydroxide or IN hydrochloric acid. The resulting mixture is useful for ocular administration, for treating, preventing, or reducing the risk of a microbial infection in a patient. Alternatively, the above formulation can be made replacing the chlorobutanol with sodium perborate, stabilized oxychloro complex, or benzalkonium chloride. Also, one or more of the following viscosity modifying agents can be added to the formulation: polyquaternium, propylene glycol, alginic acid, or sodium alginate. Example 11. Solid Formulation for Oral Administration

"removed during drying process The above ingredients are combined using standard mixing equipment and techniques as described for the other solid formulations for oral administration described above. The resulting formulation is useful for oral administration, for treating, preventing, or reducing the risk of a microbial infection in a patient.

Example 12. Solubility The solubility of the quinolone carboxylic acid compound in the solid compositions of the present invention is evaluated. For room temperature equilibrium solubility measurements, an excess of the quinolone carboxylic acid composition to be evaluated is mixed with a test vehicle. The initial pH is recorded and then the pH is adjusted to the target pH for the study with either HCl or NaOH. Samples are placed at 25 0C in a mechanical shaker for 24 to 72 hours. An aliquot is removed and filtered or centrifuged. The supernatant is decanted and the pH was measured. A sample is then diluted with methanol for HPLC analysis. Delafloxacin has a solubility of about 0.36 mg/mL at pH 7. The solubility of delafloxacin decreases to about 0.1 mg/mL at pH 7 in the present of 0.4167 mg/mL of vitamin E TPGS. Therefore, even though vitamin E TPGS appears to decrease the aqueous solubility of delafloxacin, it is surprisingly found to be useful as an absorption enhancer in the present invention.

INCORPORATION BY REFERENCE The entire disclosure of each of the patent documents, including certificates of correction, patent application documents, scientific articles, governmental reports, websites, and other references referred to herein is incorporated by reference in its entirety for all purposes.

EQUIVALENTS The invention can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. WHAT IS CLAIMED IS:

1. A pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, and (b) an absorption enhancer.

2. A pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester or prodrug thereof, and (b) an absorption enhancer.

3. A pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a basifier.

4. A pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a basifϊ er.

5. A pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a crystallization inhibitor.

6. A pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, and (c) a crystallization inhibitor.

7. A pharmaceutical composition which prior to mixing comprises (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, (c) a basifier, and (d) a crystallization inhibitor.

8. A pharmaceutical composition comprising (a) a quinolone carboxylic acid compound or a pharmaceutically acceptable salt, ester, or prodrug thereof, (b) an absorption enhancer, (c) a basifier, and (d) a crystallization inhibitor.

9. A pharmaceutical composition according to any of claims 2, 4, 6 or 8 comprising (that is in the form of) a dispersion.

10. A pharmaceutical composition according to any of claims 2, 4, 6, or 8 comprising (that is in the form of) a dry mixture.

11. A pharmaceutical composition according to any of claims 2, 4, 6, 8, 9, or 10 comprising (that is in the form of) a tablet.

12. A pharmaceutical composition according to any of claims 2, 4, 6, 8, 9, or 10 comprising (that is in the form of) a capsule. 13. A pharmaceutical composition according to any of claims 1-12 wherein said absorption enhancer is an alkoxylated tocopheryl ester.

14. A pharmaceutical composition according to claim 13 wherein said alkoxylated tocophyerl ester is an alkoxylated tocopheryl monoester.

15. A pharmaceutical composition according to any of claim 14 wherein said alkoxylated tocopheryl monoester is an alkoxylated tocopheryl monosuccinate.

16. A pharmaceutical composition according to any of claims 1-15 wherein said alkoxylated tocopheryl ester is an ethoxylated tocopheryl ester.

17. A pharmaceutical composition according to any of claims 1-16 wherein said alkoxylated tocopheryl ester is vitamin E TPGS.

18. A pharmaceutical composition according to any of claims 1-17 wherein said quinolone carboxylic acid compound corresponds to the following structure

19. A pharmaceutical composition according to claim 18 wherein said quinolone carboxylic compound corresponds to the following structure

or a pharmaceutically acceptable salt, ester, or prodrug thereof.

20. A pharmaceutical composition according to claim 19 wherein said quinolone carboxylic acid compound is D-glucitol, l-deoxy-l-(methylamino)-, l-(6-amino-3,5-difluoro- 2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l-azetidinyl)-4-oxo-3- quinolinecarboxylate (salt).

21. A pharmaceutical composition according to claim 19 wherein said quinolone carboxylic acid compound is crystalline D-glucitol, l-deoxy-l-(methylamino)-, l-(6-amino-3,5-difluoro- 2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l-azetidinyl)-4-oxo-3- quinolinecarboxylate (salt) characterized, when measured about 25 0C with Cu-Ka radiation, by the powder diffraction pattern shown in FIGURE 1.

22. A pharmaceutical composition according to claim 19 wherein said quinolone carboxylic acid compound is D-glucitol, l-deoxy-l-(methylamino)-, l-(6-amino-3,5-difluoro- 2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l-azetidinyl)-4-oxo-3- quinolinecarboxylate trihydrate (salt).

23. A pharmaceutical composition according to claim 19 wherein said quinolone carboxylic acid compound is crystalline D-glucitol, 1-deoxy-, l-(methylamino)-l-(6-amino- 3,5-difluoro-2-pyridinyl)-8-chloro-6-fluoro-l,4-dihydro-7-(3-hydroxy-l-azetidinyl)-4-oxo-3- quinolinecarboxylate trihydrate (salt) characterized, when measured about 25 0C with Cu-Ka radiation, by the powder diffraction pattern shown in FIGURE 2.

24. A pharmaceutical composition according to any of claims 3, 4, or 7-23 wherein said basifϊ er is selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, sodium carbonate, and potassium carbonate ethylene diamine, ethylene triamine, ethanolamine, diethanolaminoe, triethanolamine, arginine, lysine, meglumine, and mixtures thereof.

25. A pharmaceutical composition according to claim 24 wherein said basifϊ er is arginine.

26. A pharmaceutical composition according to any of claims 5-23 wherein said crystallization inhibitior is selected from the group consisting of polyethylene glycol, polymers of l-ethenyl-2-pyrrolidinone; polyamine N-oxide polymers; copolymers of N- vinylpyrrolidone and N-vinylimidazole; polyvinyloxazolidones and polyvinylimidazoles, mixtures thereof.

27. A pharmaceutical composition according to claim 26 wherein said crystallization inhibitor is a homopolymer of l-ethenyl-2-pyrrolidinone, especially the homopolymer, particularly a homopolymer having a molecular weight range of about 2500 to 3,000,000 amu.

28. A pharmaceutical composition according to claim 27 wherein said crystallization inhibitor is polyvinylpyrolidone K30.

29. A pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) from about 120 mg to about 600 mg of vitamin E TPGS.

30. A pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 25 mg to about 500 mg of arginine.

31. A pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 5 mg to about 100 mg of polyvinylpyrolidone K30.

32. A pharmaceutical composition comprising (a) from about 100 mg to about 500 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) from about 120 mg to about 600 mg of vitamin E TPGS, and (c) from about 25 mg to about 500 mg of arginine, and (d) from about 5 mg to about 100 mg of polyvinylpyrrolidone K30.

33. A pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) about 240 mg of vitamin E TPGS.

34. A pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg of vitamin E TPGS, and (c) about 50mg of arginine.

35. A pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg of vitamin E TPGS, and (c) about 20 mg of polyvinylpyrolidone K30.

36. A pharmaceutical composition comprising (a) about 200 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 240 mg to about 600 mg of vitamin E TPGS, and (c) about 5 mg to about 500 mg of arginine, and (d) about 20 mg of polyvinylpyrrolidone K30.

37. A pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, and (b) about 360 mg of vitamin E TPGS.

38. A pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg of vitamin E TPGS, and (c) about 75 mg of arginine.

39. A pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg of vitamin E TPGS, and (c) about 30 mg of polyvinylpyrolidone K30.

40. A pharmaceutical composition comprising (a) about 300 mg of delafloxacin meglumine, on a delafloxacin active basis, (b) about 360 mg to about 600 mg of vitamin E TPGS, and (c) about 5 mg to about 500 mg of arginine, and (d) about 30 mg of polyvinylpyrrolidone K30.

41. A composition according to any of claims 1 to 40 for oral administration.

42. A method for treating, preventing, or reducing the risk of a bacterial infection comprising administering to a patient in need thereof a composition according to any of claims 1to 41.