US 2008O160067A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0160067 A1 Boeckh et al. (43) Pub. Date: Jul. 3, 2008

(54) NOVEL SOFT CHEWABLE, TABLET, AND (22) Filed: Sep. 5, 2007 LONG-ACTING INUECTABLEVETERINARY ANTIBOTC FORMULATIONS Related U.S. Application Data (60) Provisional application No. 60/842,877, filed on Sep. (76) Inventors: Albert Boeckh, Cumming, GA 7, 2006. (US); Mark D. Soll, Alpharetta, GA Publication Classification (US); Monica Tejwani-Motwani, Somerset, NJ (US); Robert P. (51) Int. Cl. Waranis, Annandale, NJ (US); A69/68 (2006.01) Fangjun Wu, Livingston, NJ (US) A6II 3/40 (2006.01) (52) U.S. Cl...... 424/441; 514/422 Correspondence Address: (57) ABSTRACT Judy Jarecki-Black, Ph.D.J.D This document relates to formulations for combating bacte 3239 Satelite Blvd. rial infections in animals which provide for improved long Duluth, GA 30096 acting oral and injectable formulations for systemic delivery of antibiotics, which are designed to achieve high bioavail (21) Appl. No.: 11/899,282 ability.

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NOVEL SOFT CHEWABLE, TABLET, AND tors such as the physiochemical properties of the pharmaceu LONG-ACTING INUECTABLEVETERINARY tical or therapeutic agent, the condition of the host, and eco ANTIBOTC FORMULATIONS nomic factors. 0008 For example, one method of formulating a therapeu INCORPORATION BY REFERENCE tic agent for oral, topical, dermal or Subdermal administration 0001. This application claims benefit of U.S. provisional is to formulate the therapeutic agent as a paste or as an patent application Ser. No. 60/842,877 filed Sep. 7, 2006. injectable formulation and reference is made to U.S. applica 0002 All documents cited or referenced in the application tion Ser. No. 09/504,741, filed Feb. 16, 2000, issued Sep. 7, cited documents, and all documents cited or referenced herein 2004 as U.S. Pat. No. 6,787,342, entitled PASTE FORMU (“herein cited documents'), and all documents cited or refer LATIONS: Ser. No. 09/346,905, filed Jul. 2, 1999, issued enced in herein cited documents, together with any manufac May 29, 2001 as U.S. Pat. No. 6,239,112, entitled WATER turer's instructions, descriptions, product specifications, and MISCIBLE MACROLIDE SOLUTIONS: Ser. No. 09/112, product sheets for any products mentioned herein or in any 690, filed Jul. 9, 1999, issued Sep. 28, 1999 as U.S. Pat. No. document incorporated by reference herein, are hereby incor 5,958,888, entitled WATER MISCIBLE MACROLIDE porated herein by reference, and may be employed in the SOLUTIONS: Ser. No. 08/675,380, filed Jul. 2, 1996, issued practice of the invention. Mar. 3, 1998 as U.S. Pat. No. 5,723,447, entitled WATER MISCIBLE ERYTHROMYCIN SOLUTIONS: Ser. No. FIELD OF THE INVENTION 09/152,775, filed Sep. 14, 1998, issued Jan. 16, 2001 as U.S. Pat. No. 6,174,540, entitled LONG ACTING INJECTIBLE 0003. This application relates to formulations for combat FORMULATIONS CONTAINING HYDROGENATED ing bacterial infections in animals. In particular, this inven CASTOROIL; and Ser. No. 09/271,098, filed Mar. 18, 1999, tion provides for improved long-acting oral and injectable issued May 11, 2004 as U.S. Pat. No. 6,733,767, entitled formulations for systemic delivery of antibiotics, which are LIQUID POLYMERIC COMPOSITIONS FOR CON designed to achieve high bioavailability. TROLLED RELEASE OF BIOACTIVE SUBSTANCES The disclosure of these patent applications as well as the BACKGROUND OF THE INVENTION references cited therein and the references cited herein are 0004 Antibiotics area class of drugs that destroy or inhibit expressly incorporated by reference. the growth of certain types of bacteria, and are commonly 0009. Other methods of formulating therapeutic agents used to effectively control a variety of acute and chronic include placing the therapeutic agent in a solid or liquid bacterial infectious diseases in birds and animals. Antibiotic matrix for oral delivery. These methods include chewable therapy may result in killing the microorganism (bactericidal drug-delivery formulations. One problem associated with drugs) or inhibiting bacterial growth (bacteriostatic drugs). oral formulations is that the therapeutic agent often provides Antibiotics are classified as broad-spectrum or narrow-spec an unpleasant taste, aroma, or mouth feel to the formulation, trum, depending on the types of bacteria they can kill or which cause, especially in the situation with animals, the oral inhibit. The broad-spectrum antibiotics have antimicrobial formulation to be rejected by the patient. See, e.g., U.S. Pat. effect on both the Gram-positive and Gram-negative bacteria, No. 5,380,535 to Geyer et al., which provides for a lipid whereas the narrow-spectrum antibiotics only affect either based, chewable formulations for oral delivery of therapeutic the Gram-positive or the Gram-negative bacterial strains. agents, such as aspirin, ibuprofen or erythromycin, which are There are five major groups of antibiotics that are classified unpalatable to humans: U.S. Pat. No. 5,894,029 to Brown et by primary mechanism of action: cell wall synthesis inhibi al., which provides for dried puff pet foods comprising fari tors, cell membrane inhibitors, protein synthesis inhibitors, naceious materials, proteinaceous materials, such as meats or nucleic acid effectors, and folate inhibitors. Vegetable protein Sources, and optionally medicaments or 0005. The kind of antibiotic, the time period for treatment, vitamins; or U.S. Pat. No. 5,637,313 to Chau et al., which and the route of administration all vary based on the disease describes chewable dosage forms comprising a water soluble conditions and animal species. Therefore, it is generally help matrix comprising hydrogenated Starch hydrolyState bulking ful to discuss animals that are treated with antibiotics as agent and a water insoluble bulking agent. Reference is also members of one of three major groups: companion animals, made to Ser. No. 10/745,784, filed Dec. 23, 2003, now pend food animals including poultry, and utility animals such as ing, entitled NON-ANIMAL PRODUCT CONTAINING horses, which may also be considered companion animals, VETERINARY FORMULATIONS: and Ser. No. 10/222, depending upon their use. 559, filed Aug. 16, 2002, now pending, entitled NON-ANI 0006 Antibiotic therapy for food animals usually does not MAL PRODUCT CONTAINING VETERINARY FORMU extend beyond 5-10 days, while treatment of companion ani LATIONS. The disclosure of these patent applications as well mals may extend for weeks or months for many chronic as the references cited therein and the references cited herein conditions. For example, some of the pathological conditions are expressly incorporated by reference. in dogs and cats, including chronic skin diseases, chronic 0010 Traditionally, in veterinary formulations, palatabil otitis, chronic dermatitis, urinary tract infections, penetrating ity had been achieved by the inclusion of animal byproducts wounds and post-Surgical treatment, may require prolonged or flavors derived from animal sources into the formulation. or repeated systemic antibiotic administration. Long-term For example, it is customary to include attracts, such as antibiotic therapy is also often required in cases of bacterial chicken powder, liver powder, beef, ham, fish, or rawhide osteomyelitis. derived products in dog chews to make the chew palatable to 0007 Generally, antibiotics are administered by a variety the dog. See, e.g., U.S. Pat. No. 6,086,940; U.S. Pat. No. of routes including, for example, oral ingestion, topical appli 6,093441; U.S. Pat. No. 6,159,516; U.S. Pat. No. 6,110,521; cation or parental administration. The particular route of U.S. Pat. No. 5,827,565; U.S. Pat. No. 6,093,427, all to Axel administration selected by the practitioner depends upon fac rod et al. However, the use of animal products or byproducts US 2008/01 60067 A1 Jul. 3, 2008

or flavors derived from animal sources have recently fallen that must be considered in selecting an appropriate type of into disfavor because of the possibility of chemical or bio antibiotic and administration route for therapy. logical contamination, which lead to toxicity or diseases Such 0014. The particular dosage form varies based upon the as bovine spongiform encephalopathy. Hence, there is a need kind of antibiotic used, the animal species being treated, and for oral veterinary formulations that do not contain animal on whether the type of infection being treated requires local or products, byproducts, or flavors derived from animal sources systemic delivery. The advantage of local antibiotic therapy while still exhibiting good organoleptic properties. While compared with systemic therapy is that a high concentration non-animal derived products such as Valerian plants are know of antibacterial is delivered locally, thus avoiding the adverse as scent attractants in food products or pet toys (U.S. Pat. No. effects that are associated with systemic antibacterial therapy. In general, companion and utility animals may be treated with 5,785.382 to Childers-Zadah) or animal chews that contain a greater variety of therapeutic options than food animals, fruit flavors as the attractant (see, U.S. Pat. Nos. 6,274,182: which are generally treated through systemic antibiotic 6,200,616 and 6,126,978 to Axelrod et al.), these patents do administration. Local delivery of antibiotic is preferred or not describe using Valerian plants or fruit flavors in oral for practical for some types of diseases in companion and utility mulations in which the pharmaceutical agents needs to be animals. For example, doxycycline-loaded biodegradable masked. polymer gel has been used to treat periodontal disease in 0011. Another problem associated with oral formulations beagles. On the other hand in horses, antibiotics are com relates to “bioavailability”, which indicates the percentage of monly used systemically for treatment of respiratory disease, a drug dose which reaches its site of action, or a biological wound infections, sinus infections, and neonatal sepsis. fluid, from which the drug has access, to its site of action Because of the large size of the horses and susceptibility to (Grant R. Wilkinson, Goodman & Gilman's The Pharmaco antibiotic induced diarrhea and colitis, there exists a need to logical Basis of Therapeutics, Tenth Ed., 5 (Hardman, J. G., improve localized delivery of antibiotics in the equine Limbird, L. E., and Gilman, A.G., eds., McGraw-Hill, 2001) patients. (1941). The bioavailability of drugs is a complex issue. For 0015 The common approaches for systemic delivery of example, a drug given orally must be absorbed first from the antibiotics are through oral and parenteral administration. stomach and intestine, but this may be limited by the charac The routes of parenteral injection could be intravenous, intra teristics of the dosage form and/or the drug's physicochemi muscular or Subcutaneous. However, intravenous administra cal properties. In addition drug then passes through the liver, tion may not be feasible or practical in species other than where metabolism and/or biliary excretion may occur before companion animals and utility animals such as horses, due to it reaches the systemic circulation. Accordingly, a fraction of labor cost and management practices. the administered and absorbed dose of drug will be inacti 0016. Antibiotics are used for three major purposes in vated or diverted before it can reach the general circulation farm animals: (a) to treat an individual or an outbreak of and be distributed to its sites of action. If the metabolic or bacterial infection (treatment), (b) to prevent outbreaks of excretory capacity of the liver for the agent in question is bacterial disease in animals at risk during certain phases of large, bioavailability will be substantially reduced (the so production (prophylaxis) and (c) to use the antibiotics in called first pass effect). This decrease in availability is a animal feed for growth promotion effects (growth promoter). function of the anatomical site from which absorption takes Growth promoters and some prophylactic antibiotics are nor place; other anatomical, physiological, and pathological fac mally administered orally via feed or drinking water. tors can influence bioavailability and the choice of the route of 0017 Drinking water and feed medication are preferred administration must be based on an understanding of these for poultry, mainly because of the large number of birds conditions (Grant R. Wilkinson, Goodman & Gilman's The involved. However, therapeutic levels of antibiotics may not Pharmacological Basis of Therapeutics, Tenth Ed., 5 (Hard be achieved due to inadequate feed or water uptake by an man, J. G., Limbird, L. E., and Gilman, A.G., eds., McGraw individual sick bird, instability of the antibiotics in feed or Hill, 2001) (1941). water, or inappropriate feeding time and techniques. There 0012. One obvious way to change the bioavailability of a fore, in the case of serious disease, parenteral administration therapeutic agent is to change the route of administration of the antibiotics for the sickbirds can be a viable alternative; from, for example, oral to parenteral. However, the use of however, the therapy is rarely used. Parenteral administration parenteral injection may not always be appropriate. For of the antibiotics is time and labor consuming for the owner, example, intravenous injection has an increased risk of and stressful for the sickbirds, because multiple injections of adverse effects and is not suitable for oily solutions or a conventional injectable formulation are often required. insoluble Substances. Subcutaneous injections are not suit 0018 Parenteral administration of antibiotics is often pre able for large Volumes and may present possible pain or ferred as a treatment mode for food animals. Therefore, anti necrosis from irritating Substances. Other strategies include biotic treatment of pastured animals or large companion ani increasing drug potency, changing dosage regimens, or using mals generally requires confinement of these animals for the combination therapies. Furthermore, the choice of pharma duration of therapy. However, repeated restraint and admin ceutical formulation plays a role in rendering the therapeutic istration within a relatively short period of time add to the agent effective upon administration. stress of illness and may complicate convalescence and 0013 Antibiotic usage in veterinary medicine presents recovery. Even docile animals tend to become fractious and other unique considerations. Animal patients vary from Small uncooperative after multiple days of parenteral therapy. companion animals and birds that live in intimate proximity 0019. It is therefore evident from the foregoing description to their owners to pastured food and fiber producing animals that there are advantages of systemic or local delivery of with little human contact. The animal species, their human long-acting antibiotic formulations to food producing and contact, temperament, size, use, emotional and economic companion animals, and birds for the treatment of infectious value, and pathological conditions are all important factors diseases. Some of these advantages include improved patient US 2008/01 60067 A1 Jul. 3, 2008

compliance, convenience for the owner and Veterinarians, and Scopelianos et al. 5,607,686 Totakura et al. 5,609,886 Wan improved cost effectiveness of treating bacterial diseases. tier et al. 5,631,015 Bezwada et al. 5,654,010 Herbert et al. Long-acting antibiotic formulations can even reduce the 5,700,485 Johnson et al. 5,702.717 Berde et al. 5,711,968 amount of antibiotics used for therapy and/or prophylaxis in Tracy et al. 5,733,566 Lewis 4,938,763 Dunn et al. 5,077,049 food animals, since the convenient and easily administered Dunn et al. 5,278,201 Dunn et al. 5,278,202 Dunn et al. long-acting formulations make it possible to treat each 5,288,496 Lewis 5,324,519 Dunn et al. 5,324,520 Dunn et al. affected animal in a more efficient and effective manner. 5,340,849 Dunn et al. 5,368,859 Dunn et al. 5,401,507 Lewis 0020 Several different approaches to develop long-acting 5,419,910 Lewis 5,427,796 Lewis 5,487,897 Polson et al. antibiotic formulations have been explored. These include 5.599,552 Dunnet al. 5,632,727 Tipton et al. 5,643,595 Lewis formulating oral dosage forms, injectable formulations such 5,660,849 Polson et al. 5,686,092 Lewis et al. 5,702,716 as Suspensions, concentrated solutions, injectable gels and Dunn et al. 5,707,647 Dunn et al. 5,717,030 Dunn et al. microparticles and implants. The selection of the develop 5,725,491 Tipton et al. 5,733,950 Dunnet al. 5,736,152 Dunn ment approach of long-acting antibiotic formulations is deter etal. 5,744,153Yewey et al. 5,759,563 Yewey et al. 5,780,044 mined by the intended application criteria, such as type of Yewey et al. disease, systemic or local therapy, short-term or long-term 0025. These documents tend to provide compositions that therapy and type of animals being treated. form a solid, gel or coagulated mass; for instance, a signifi 0021 Biodegradable polymers have been used in cant amount of polymer is contemplated in these documents, parenteral controlled release formulations of bioactive com akin to European Patent Application 0537559. pounds. Gels prepared with biodegradable polymers such as 0026 Mention is also made of Shah et al (J. Controlled poly(lactide-co-glycolide), poly(lactic acid) and polyoxyeth Release, 1993, 27:139-147), as relating to formulations for ylene polyoxypropylene block copolymers (poloxamers or, Sustained release of bioactive compounds containing various LUTROL(R) F) and biocompatible, non-toxic solvents, such concentrations of poly(lactic-co-glycolic) acid copolymer as triethylcitrate and acetyl triethylcitrate or water have been (PLGA) dissolved in vehicles such as triacetin: Lambert and used to develop long-acting antibiotics formulations. The Peck (J. Controlled Release, 1995,33:189-195), as a study of reversible thermal gelation characteristics of the formulations the release of protein from a 20% PLGA solution in N-me allowed the liquid injection to gel at the injection site at body thylpyrrolidone exposed to aqueous fluid; and Shivley etal (J. temperature. Controlled Release, 1995, 33:237-243), as a study of the 0022. In one approach the polymer is fabricated into solubility parameter of poly(lactide-co-glycolide) copolymer microspheres that may be injected via syringe, and the bio in a variety of solvents, and the in vivo release of naltrexone active compound is entrapped within the microspheres. This from two injectable implants (5% maltrexone in either 57% approach has not proved to be practical in part due to the PLGA and 38% N-methylpyrrolidone or 35% PLGA and difficulty in the manufacturing procedure for producing ster 60% N-methylpyrrolidone). ile and reproducible products, and the high cost of manufac 0027 Various other gel-forming agents have been studied turing. In another approach the biodegradable polymer and for usefulness as carriers for therapeutic agents, for example the bioactive material are dissolved in a biocompatible water poloxamers. Poloxamers are a family of more than 30 differ miscible solvent to provide a liquid composition. When the ent nontoxic nonionic Surface active agents. Concentrated liquid composition is injected into the body, the Solvent dis aqueous solutions of many of the poloxamers form gels, a sipates into the Surrounding aqueous environment, and the property that reverses upon a decrease in temperature, where polymer forms a solid depot from which the bioactive mate upon the gel reverts to a liquid. rial is released. 0028. The use of poloxamers as delivery vehicles, such as 0023 European Patent Application 0537559 concerns controlled or Sustained release systems, gels, microemulsions polymeric compositions having athermoplastic polymer, rate and nanoparticles may provide enhanced solubility of thera modifying agent, water soluble bioactive material and water peutic agents, enhanced bioavailability, lengthened contact at miscible organic solvent. Upon exposure to an aqueous envi specifically selected sites in the body, combined with the ronment (e.g. body fluids) the liquid composition is capable reduction in quantity of applied drug. All of these aspects may of forming a biodegradable microporous, Solid polymer be exploited in order to optimize systemic and minimize side matrix for controlled release of water soluble or dispersible effects of active drugs. bioactive materials over about four weeks. The thermoplastic (0029 Chowdhury et al., U.S. Publication No. polymer may be, among many listed, polylactide, polygly 20040087520, in part discusses the usefulness of poloxamers collide, polycaprolactone or copolymers thereof, and is used for topical or ophthalmic delivery of various therapeutic in high concentration (45 to 50%). The rate modifying agent agents, including antibiotics. In this regard, this reference is may be, among many others listed, glycerol triacetate (triace primarily involved with studies of localized application of tin); however, only ethylheptanoate is exemplified; and the antibiotics at a Surgical site to prevent Surgical site infections. amount of the rate modifying agent is no more than 15%. 0030 Poloxamers have also been investigated for useful 0024 Indeed, with respect to the patent literature, refer ness in controlled release injectable gel formulations. For ence is made to: INVENTORU.S. Pat. Nos. 4,150,108 Gra example, when injected intramuscularly, the formulation ham 4,329,332 Couvreuretal. 4.331,652 Ludwig et al. 4.333, forms a depot for the controlled release of drug by gelling at 919 Kleber et al. 4,389,330 Tice et al. 4,489,055 Couvreur et body temperature. Paavola, et al., investigated a method of al. 4,526,938 Churchill et al. 4,530,840 Tice et al. 4,542,025 delaying the action of a local anesthetic, lidocaine, in post Tice et al. 4,563,489 Urist 4,675,189 Kent et al. 4,677,191 operative and chronic pain using a low-viscosity gel contain Tanaka et al. 4,683.288 Tanaka et al. 4,758,435 Schaaf 4,857, ing a poloxamer (Paavola, A. et al., Pharm. Res. Vol. 12, No. 335 Bohm 4,931,287 Bae et al. 5,178,872 Ohtsubo et al. 12, 1995). The 2% lidocaine-containing gels were evaluated 5.252,701 Jarrett etal. 5.275,820 Chang 5,478,564 Wantier et in rats. Based on the results, compared to other carriers, the al. 5,540,912 Roorda et al. 5,447,725 Damani et al. 5,599,852 poloxamer gel was held to be the most effective, providing US 2008/01 60067 A1 Jul. 3, 2008

release of lidocaine for up to 240 minutes. The reference did ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, not discuss the feasibility of using gels as injectable Sus cephalothin, cephamandole, cephapirin, cepharadine, ceph tained-release vehicles for antibiotics or any other therapeutic prozil, chloramphenicol, chlortetracycline, ciprofloxacin, agents. clarithromycin, clindamycin HCl, clindamycin or salts 0031. Another formulation approach of developing long thereof, clindamycin phosphate, clofazimine, cloxacillin, acting injectable formulations is to prepare concentrated colistin, co-triamoxazole, cycloserine, dalfopristin, danof Solutions of antibiotics for injection, using Suitable pharma loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro ceutically acceptable water-miscible solvents such as poly streptomycin, dirithromycin, docycycline, efrotomycin, ethylene glycol, propylene glycol, n-methylpyrrolidone, and enoxacin, enrofloxacin, ertapenem, erythromycin and salts 2-pyrrolidone. After an intramuscular or Subcutaneous injec thereof, ethambutol HCl and other salts, ethionamide, flo tion of the concentrated antibiotic solution, the drug precipi rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy tates at the injection site since the water-miscible solvent is carried away or diluted by the biological fluids, or absorbed cin, gatifloxacin, gentamycin, imipenem, imipenemi-cilastin, rapidly from the injection site. The precipitated drug particles isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, are slowly dissolved in the biological fluid at the site of lomefloxacin, loracarbef mafenide, marbofloxacin, mero injection, and the dissolved drug is absorbed into the blood penem, methenamine, methicillin, metronidazole, mezlocil Stream. lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo 0032. Although most of the antibiotics currently on the mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, market can generally be used in any animal species, develop ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy ing a long-acting formulation which is suitable requires con cline, paromomycin, penicillin G, penicillin Gaqueous, peni sideration of the size of animal species, physiological features cillin G benzatine, penicillin G procaine, penicillin V, peni of the animal, diseases to be treated, and the economic and cillin V penicillin salts and complexes, pentamidine, emotional interest of the animal owners. piperacillin, piperacillin sodium, piperacillin-taZobactam, 0033. With all of the above factors at play in the develop polymixin B. pyrazinamide, rifampin, roXithromycin, salts of ment of antibiotic formulations, it remains a challenge to carbenicillin, silver Sulfadiazine, sparfloxacin, spectinomy develop long-acting injectable formulations that remain cin, spiramycin, Streptomycin, Streptozocin, Sufadimethox effective for a sufficiently long time in order that a single ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, injection is all that is necessary. The present invention fulfills Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam this long-felt need. erazine, sulfamethazine, sulfamethixole, sulfapyridine, Sul 0034) Citation or identification of any document in this fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, application is not an admission that such document is avail taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia able as prior art to the present invention. mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi SUMMARY OF THE INVENTION cosin, tobramycin, trimethoprim, trimetrexate and ketolides, troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco 0035. The present invention relates to novel chewable and mycin and ketolides such as tellithromycin and HMR 3004. tablet veterinary formulations that provide bioavailability of 0039 More advantageously, the chewable formulation antibiotics that is comparable to a conventional capsule prod comprises an antibiotic that is clindamycin or a pharmaceu uct. This invention further provides for improved veterinary tically acceptable salt or hydrate thereof. Most advanta formulations or which possess good consistency and accept geously, the antibiotic is clindamycin HC1. ability by the animal, as well as a process to prepare said veterinary formulations. The invention further relates to a 0040 Advantageously, the chewable formulation com long-acting injectable formulation that provides Sustained prises a hydrophobic material selected from the group con concentrations of therapeutic agents for 7-10 days. sisting of glyceryl behenate, hydrogenated vegetable oil, 0036. The present invention encompasses a chewable vet Stearic acid, glyceryl monostearate, glycerylpalmito Stearate erinary formulation which may comprise an antibiotic, a or cetyl alcohol. Most advantageously, the hydrophobic hydrophobic material, a filler, a disintegrant, a solvent, and material is hydrogenated vegetable oil. optionally a flavor, and optionally a preservative. 0041 Advantageously, the chewable formulation com 0037. In one embodiment, the formulation comprises an prises a filler selected from the group consisting of soy pro antibiotic between 1 and 5% of the formulation, a hydropho tein, corncob, or corn glutton meal. More advantageously, the bic material between 2 and 15%, soy protein fines between filler is soy protein. 20-60%, flavor between 5-30%, preservative between 0.2 to 0042 Advantageously, the chewable formulation com 1%, disintegrant between 2 and 10%, and solvent between 2 prises a flavor wherein the flavor is a hickory smoke flavor or and 20%. a beef flavor. 0038 Advantageously, the antibiotic of the chewable for 0043 Advantageously, the chewable formulation com mulation is selected from the group consisting of amikacin, prises a preservative selected from the group consisting of aminosalicyclic acid, amoxicillin, amoxicillin and clavulan parabens (methylparaben and/or propylparaben), benzalko ate potassium, amplicillin, azithromycin, bacampicillin, baci nium chloride, benzethonium chloride, benzoic acid, benzyl tracin, capreomycin, carbenicillin, carbenicillin indanyl alcohol, bronopol, butylparaben, cetrimide, chlorhexidine, Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, cefazolin, cefazolin Sodium, cefepime, cefinetazole, methylparaben, phenol, phenoxyethanol, phenylethyl alco cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, hol, phenylmercuric acetate, phenylmercuric borate, phe ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin nylmercuric nitrate, potassium Sorbate, Sodium benzoate, Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, Sodium propionate, Sorbic acid, thimerosal, propyl paraben, cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, myristylgama-picolinium chloride, paraben methyl, paraben US 2008/01 60067 A1 Jul. 3, 2008 propyl and quaternary ammonium compounds. More advan rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy tageously, the preservative is methylparaben and/or propylpa cin, gatifloxacin, gentamycin, imipenem, imipenemi-cilastin, raben. isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, 0044 Advantageously, the chewable formulation com lomefloxacin, loracarbef mafenide, marbofloxacin, mero prises a disintegrant selected from the group consisting of penem, methenamine, methicillin, metronidazole, mezlocil Sodium starch glycolate, crospovidone, croScarmellose lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo Sodium, starch, micocrystalline cellulose, alginic acid, vee mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, gum, crospovidone, bentonite, and pregelatinized starch. ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy More advantageously, the disintegrant is crospovidone. cline, paromomycin, penicillin G, penicillin Gaqueous, peni 0045 Advantageously, the chewable formulation com cillin G benzatine, penicillin G procaine, penicillin V, peni prises a humectant is selected from the group consisting of propylene glycol, glycerin, polyethylene glycol 400 and cillin V penicillin salts and complexes, pentamidine, polyethylene glycol 3350. More advantageously, the humec piperacillin, piperacillin sodium, piperacillin-taZobactam, tant is propylene glycol or purified water. polymixin B. pyrazinamide, rifampin, roXithromycin, salts of 0046. The chewable formulations are prepared according carbenicillin, silver Sulfadiazine, sparfloxacin, spectinomy to methods conventional in the art, such as wet and dry granu cin, spiramycin, Streptomycin, Streptozocin, Sufadimethox lation processes. ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, 0047 Advantageously, the process for preparing a chew Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam able formulation comprises the steps of erazine, Sulfamethazine, Sulfamethixole, Sulfapyridine, Sul 0048 (a) blending the pharmaceutical agent, hydropho fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, bic material, disintegrant, flavor, taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia 0049 (b) adding the water, preservative, and the humec mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi tant to the mixture from step (a) and mixing the mixture; cosin, tobramycin, trimethoprim, trimetrexate and ketolides, and troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco 0050 (c) without drying, extruding the mixture. mycin and ketolides such as tellithromycin and HMR 3004. 0051) Advantageously, administration of the chewable 0056 More advantageously, the tablet formulation com formulation of the present invention achieves bioavailability prises an antibiotic that is clindamycin or a pharmaceutically in an animal of a therapeutic agent that is comparable to acceptable salt or hydrate thereof. Most advantageously, the commercially available products, and effectively treats bac antibiotic is clindamycin HC1. terial infections in an animal. 0057 Advantageously, the tablet formulation comprises a 0.052 The time course of treatment to be administered is filler selected from the group consisting of anhydrous lactose, easily determined by one skilled in the art. Advantageously, hydrated lactose, sprayed dried lactose, crystalline maltose the animal receives treatment on days 0, 7, 14, 21, and 28. and maltodextrins. More advantageously, the filler is lactose. 0053. The present invention further encompasses a tablet 0.058 Advantageously, the tablet formulation comprises a Veterinary formulation comprising an antibiotic, a lactose binder selected from the group consisting of polyvinyl pyr carrier, mannitol, a binder and disintegrant, an aqueous sol rolidone, povidone, starch, pregelatinized Starch, gelatin, vent, and optionally a flavor, and optionally color. methylcellulose, hydroxypropyl cellulose, carboxymethyl 0054. In one embodiment, the tablet formulation com cellulose Sodium, ethylcellulose, Sodium alginate, traga prises an antibiotic between 4 and 15%, a lactose carrier canth, and acacia. More advantageously, the binder is poly between 40 and 80%, mannitol between 5 and 15%, a binder vinyl pyrrolidone. and disintegrant between 3 and 10%, flavor between 10 and 0059 Advantageously, the tablet formulation comprises a 20%, color between 0.1 and 0.5%, and aqueous solvent is of disintegrant selected from the group consisting of sodium a concentration sufficient to q.s. to 100%. starch glycolate, crospovid one, croScarmellose Sodium, 0055 Advantageously, the antibiotic of the tablet formu starch, micocrystalline cellulose, alginic acid, veegum, lation is selected from the group consisting of amikacin, crospovidone, bentonite, and pregelatinized starch. More aminosalicyclic acid, amoxicillin, amoxicillin and clavulan advantageously, the disintegrant is crospovidone. ate potassium, amplicillin, azithromycin, bacampicillin, baci 0060 Advantageously, the tablet formulation comprises a tracin, capreomycin, carbenicillin, carbenicillin indanyl flavor, wherein the flavor is a hickory smoke flavor or a beef Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, flavor. cefazolin, cefazolin Sodium, cefepime, cefinetazole, cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, 0061 Advantageously, the tablet formulation comprises a ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin colorant selected from the group consisting of dyes, an alu Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, minum lake, caramel, colorant based upon iron oxide or a cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, mixture of any of the foregoing. More advantageously, the ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, colorant is selected from the group consisting of organic dyes cephalothin, cephamandole, cephapirin, cepharadine, ceph and titanium dioxide. prozil, chloramphenicol, chlortetracycline, ciprofloxacin, 0062) Advantageously, the process for preparing a tablet clarithromycin, clindamycin HCl, clindamycin or salts formulation comprises the steps of mixing the ingredients thereof, clindamycin phosphate, clofazimine, cloxacillin, intimately and pressing into single scored tablets. colistin, co-triamoxazole, cycloserine, dalfopristin, danof 0063 Advantageously, administration of the tablet formu loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro lation of the present invention achieves bioavailability in an streptomycin, dirithromycin, docycycline, efrotomycin, animal of a therapeutic agent that is comparable to commer enoxacin, enrofloxacin, ertapenem, erythromycin and salts cially available products, and effectively treats bacterial thereof, ethambutol HCl and other salts, ethionamide, flo infections in an animal. US 2008/01 60067 A1 Jul. 3, 2008

0064. The time course of treatment to be administered is acceptable salt or hydrate thereof. Most advantageously, the easily determined by one skilled in the art. Advantageously, antibiotic is clindamycin phosphate. the animal receives treatment on days 0, 7, 14, 21, and 28. 0070 Advantageously, the poloxamer of the LAI formu 0065. The present invention further encompasses novel lation is selected from any available poloxamer. More advan long-acting injectable (LAI) formulations that provide slow tageously, the poloxamer is selected from the group consist release of therapeutic agent and which thereby provide Sus ing of any LUTROL(R). More advantageously, the poloxamer tained concentrations of therapeutic agent, lasting anywhere is LUTROLOR F 127 or LUTROLOR F 68. from 7-10 days. Such a dosage regimen allows for conve 0071 Advantageously, the process for preparing the LAI nience in administration, increases in compliance, and Veterinary formulation comprises the steps of: decreases in error in treatment. 0.072 (a) stirring the poloxamer into purified water at 5° 0066. In one embodiment, the LAI formulation comprises C.; an antibiotic, one or more poloxamers or other similar gelling 0.073 (b) optionally adding a second poloxamer to the agents, and sterile water for injection. mixture from step (a) and mixing the mixture; and 0067. Advantageously, the LAI formulation comprises an 0.074 (c) optionally adding a polyacrylic acid into an antibiotic between 9 and 18%, a poloxamer between 5 and aliquot of water, and completely hydrating the poly 30%, and sterile water for injection of a concentration suffi acrylic acid before mixing it into the poloxamer Solution cient to q.s. to 100%. at 5° C.; 0068 Advantageously, the antibiotic of the LAI formula 0075 (d) neutralizing the Carbopol using triethanola tion is selected from the group consisting of amikacin, ami 1C. nosalicyclic acid, amoxicillin, amoxicillin and clavulanate 0.076 (e) dissolving the drug in ethanol/propylene gly potassium, amplicillin, azithromycin, bacampicillin, bacitra col and adding it to the above Solution. cin, capreomycin, carbenicillin, carbenicillin indanyl 0077 Advantageously, administration of the LAI formu Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, lation of the present invention provides slow release of anti cefazolin, cefazolin Sodium, cefepime, cefinetazole, biotic and Sustained concentrations of therapeutic agent, last cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, ing anywhere from 7-10 days, and thereby effectively treats ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin bacterial infections in an animal with a single injection. The Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, time course of treatment to be administered is easily deter cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, mined by one skilled in the art. Advantageously, a single ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, injection is necessary for therapeutic agents, the effectiveness cephalothin, cephamandole, cephapirin, cepharadine, ceph of which is desired for between 7 and 10 days. Wherein a prozil, chloramphenicol, chlortetracycline, ciprofloxacin, prolonged effect is desired, Subsequent injections may be clarithromycin, clindamycin HCl, clindamycin or salts required every 7-10 days. thereof, clindamycin phosphate, clofazimine, cloxacillin, colistin, co-triamoxazole, cycloserine, dalfopristin, danof 0078. These and other embodiments are disclosed or are loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro obvious from and encompassed by, the following Detailed streptomycin, dirithromycin, docycycline, efrotomycin, Description. enoxacin, enrofloxacin, ertapenem, erythromycin and salts thereof, ethambutol HCl and other salts, ethionamide, flo BRIEF DESCRIPTION OF THE DRAWINGS rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy cin, gatifloxacin, gentamycin, imipenem, imipenemi-cilastin, 007.9 FIG. 1 illustrates the mean concentrations of clin isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, damycin in dog serum after treatment with soft chewable or lomefloxacin, loracarbef mafenide, marbofloxacin, mero hard chewable formulations as compared to the commercial penem, methenamine, methicillin, metronidazole, mezlocil product, ANTIROBER). lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, DETAILED DESCRIPTION ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy cline, paromomycin, penicillin G, penicillin Gaqueous, peni 0080. As used herein, the following terms have the mean cillin G benzatine, penicillin G procaine, penicillin V, peni ings ascribed to them unless specified otherwise. In this dis cillin V penicillin salts and complexes, pentamidine, closure, “comprises.” “comprising.” “containing” and "hav piperacillin, piperacillin sodium, piperacillin-taZobactam, ing” and the like can have the meaning ascribed to them in polymixin B. pyrazinamide, rifampin, roXithromycin, salts of U.S. Patent law and can mean “includes,” “including,” and the carbenicillin, silver Sulfadiazine, sparfloxacin, spectinomy like: “consisting essentially of or “consists essentially like cin, spiramycin, Streptomycin, streptozocin, Sufadimethox wise has the meaning ascribed in U.S. Patent law and the term ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, is open-ended, allowing for the presence of more than that Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam which is recited so long as basic or novel characteristics of erazine, Sulfamethazine, Sulfamethixole, Sulfapyridine, Sul that which is recited is not changed by the presence of more fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, than that which is recited, but excludes prior art embodi taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia mentS. mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi I0081. The phrases “oral bioavailability” and “bioavail cosin, tobramycin, trimethoprim, trimetrexate and ketolides, ability upon oral administration” as used herein refer to the troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco systemic availability (i.e., blood/plasma levels) of a given mycin and ketolides such as tellithromycin and HMR 3004. amount of antibiotic administered to a patient. 0069. More advantageously, the LAI formulation com 0082. The term “clearance' as used herein refers to the prises an antibiotic that is clindamycin or a pharmaceutically removal of a Substance from the blood, e.g., by renal excre US 2008/01 60067 A1 Jul. 3, 2008

tion, expressed interms of the volume flow of blood or plasma cin, nafcillin, nalidixic acid, neomycin, netilmicin, nitro that would contain the amount of substance removed per unit furantoin, norfloxacin, novobiocin, ofloxacin, orbifloxacin, time. ormetoprim, oxacillin, oxytetracycline, paromomycin, peni 0083. The term “half-life' as used herein refers to the cillin G, penicillin G aqueous, penicillin G benzatine, peni period of time required for one-half of an amount of a sub cillin G procaine, penicillinV, penicillinV penicillin salts and stance to be lost through biological processes. complexes, pentamidine, piperacillin, piperacillin Sodium, I0084. The term “bioavailability” as used herein refers to piperacillin-taZobactam, polymixin B. pyrazinamide, the physiological availability of a given amount of a drug, as rifampin, roxithromycin, salts of carbenicillin, silver sulfadi distinct from its chemical potency. The term may also refer to azine, sparfloxacin, spectinomycin, spiramycin, Streptomy the proportion of the administered dose which is absorbed cin, Streptozocin, Sufadimethoxine-ormetoprim, Sulfaceta into the bloodstream. mide, Sulfacytine, Sulfadiazine, Sulfadimethoxine, 0085. The term “animal' is used herein to include all ver Sulfadimethoxine-trimethoprim, Sulfamerazine, Sulfamet tebrate animals, including humans. It also includes an indi hazine, Sulfamethixole, Sulfapyridine, Sulfapyrizine, Sul vidual animal in all stages of development, including embry fasalazine, Sulfinethoxazole, Sulfisoxazole, taZobactam, onic and fetal stages. As used herein, the term “production teicoplanin, tetracycline, tetracycline HCl, tiamulin, ticarcil animals” is used interchangeably with “livestock animals' lin, ticarcillin and clavulanate potassium, tilmicosin, tobra and refers generally to animals raised primarily for food. For mycin, trimethoprim, trimetrexate and ketolides, troleano example, Such animals include, but are not limited to, cattle mycin, trovafloxacin, tulathromycin, tylosin, Vancomycin (bovine), sheep (ovine), pigs (porcine or Swine), poultry and ketolides such as tellithromycin and HMR 3004. (avian), and the like. As used herein, the term “cow’ or "cattle' is used generally to refer to an animal of bovine origin I0088. The amount of therapeutic agent depends on the of any age. Interchangeable terms include “bovine”, “calf. individual therapeutic agent, the animal being treated, the “steer”, “bull”, “heifer”, “cow’ and the like. As used herein, disease state, and the severity of the disease state. The deter the term "pig is used generally to refer to an animal of mination of those factors is well within the skill level of the porcine origin of any age. Interchangeable terms include practitioner. “piglet”, “sow’ and the like. I0089 Preferred formulations are those containing about I0086. In a first embodiment, the present invention pro 0.01 to 50% w/w of therapeutic agent and especially preferred vides for a soft chewable veterinary formulation, which com formulations are those containing about 2.5 to about 5% w/w prises an effective amount of therapeutic agent which com of therapeutic agent. prises at least one antibiotic, a hydrophobic material, at least 0090 Advantageously, the soft chewable formulation one filler, at least one disintegrant, at least one product con contains as an antibiotic, clindamycin, or salts thereof. Most taining flavor, at least one preservative, and at least one preferred is clindamycin HCl in a range of 1-5% w/w. humectant. 0091 For soft chewable formulations, the hydrophobic 0087. For soft chewable formulations, the antibiotic may material may include Surfactants of different degrees of be selected from the following, which is to be considered hydrophobicity or hydrophilicity which can be prepared by non-limiting: beta lactam, semisynthetic penicillins, bacitra reaction of alcohols or polyalcohols with a variety of natural cin, cephalosporins, quinolones, fluorinated quinolones, and/or hydrogenated oils. Most commonly, the oils used are polymyxin, tetracyclines, chloramphenicol, macrollides, ami castor oil or hydrogenated castor oil, or an edible vegetable oil noglycosides, nalidixic acid, rifamycins, and Sulfonamides. Such as corn oil, olive oil, peanut oil, palm kernel oil, apricot Some examples include Amikacin, aminosalicyclic acid, kernel oil, soybean oil, or almond oil. Preferred alcohols amoxicillin, amoxicillin and clavulanate potassium, amplicil include glycerol, propylene glycol, ethylene glycol, polyeth lin, azithromycin, bacampicillin, bacitracin, capreomycin, ylene glycol, Sorbitol, and pentaerythritol. Among these alco carbenicillin, carbenicillin indanyl Sodium, cefaclor, hol-oil transesterified surfactants, preferred hydrophilic Sur cefadroxil, cefaloridine, cefamandole, cefazolin, cefazolin factants are PEG-35 castor oil (Incrocas-35), PEG-40 Sodium, cefepime, cefinetazole, cefixime, cefinetazole, cefo hydrogenated castor oil (Cremophor RH 40), PEG-25 tri dizime, cefonicid, cefoperaZone, ceforanide, cefotaxime, oleate (TAGATR TO), PEG-60 corn glycerides (Crovol cefotetan, cefoxitin, cefoxitin Sodium, cefpirome, cefpo M70), PEG-60 almond oil (Crovol A70), PEG-40 palm kernel doXime, cefpodoxime proxetil, cefiguinome, ceftaxidime, oil (Crovol PK70), PEG-50 castor oil (Emalex C-50), PEG ceftibuten, ceftiofur, ceftizoxime, ceftriaxone, cefuroxime, 50 hydrogenated castor oil (Emalex HC-50), PEG-8 caprylic/ cephacelor, cephadrine, cephalexin, cephalothin, cephaman capric glycerides (Labrasol), and PEG-6 caprylic/capric dole, cephapirin, cepharadine, cephprozil, chloramphenicol, glycerides (Softigen 767). Preferred hydrophobic surfactants chlortetracycline, ciprofloxacin, clarithromycin, clindamy in this class include PEG-5 hydrogenated castor oil, PEG-7 cin HCl, clindamycin or salts thereof, clindamycin phos hydrogenated castor oil, PEG-9 hydrogenated castor oil, phate, clofazimine, cloxacillin, colistin, co-triamoxazole, PEG-6 corn oil (Labrafil R. M. 2125 CS), PEG-6 almond oil cycloserine, dalfopristin, danofloxacin, demeclocycline, (Labrafil RM 1966 CS), PEG-6 apricot kernel oil (Labrafil.R. dicloxacillin, difloxacin, dihydro-streptomycin, dirithromy M1944CS), PEG-6 olive oil (Labrafil RM 1980 CS), PEG-6 cin, docycycline, efrotomycin, enoxacin, enrofloxacin, ertap peanut oil (Labrafil R. M. 1969 CS), PEG-6 hydrogenated enem, erythromycin and salts thereof, ethambutol HCl and palm kernel oil (Labrafil.R M 2130 BS), PEG-6 palm kernel other salts, ethionamide, florfenicol, flumequine, fosfomycin, oil (Labrafil.R M 2130 CS), PEG-6 triolein (Labrafil.R M fosfomycin, gamithromycin, gatifloxacin, gentamycin, imi 2735CS), PEG-8 corn oil (Labrafil R. WL 2609 BS), PEG-20 penem, imipenemi-cilastin, isoniazid, kanamycin, levofloxa corn glycerides (Crovol M40), and PEG-20 almond glycer cin, lincomycin, lineZolid, lomefloxacin, loracarbef ides (Crovol A40). mafenide, marbofloxacin, meropenem, methenamine, methi 0092 Preferred formulations are those containing about cillin, metronidazole, meZlocillin, minocycline, moxifloxa 0.01 to 50% w/w of hydrophobic material and especially US 2008/01 60067 A1 Jul. 3, 2008

preferred formulations are those containing about 1 to about smoke solution, sold by Red Arrow Products Co. as CHAR 20% w/w of hydrophobic material. TOR HICKORY or a hickory smoke flavoring produced by 0093 Advantageously, the soft chewable formulation combining maltodextin with an aqueous hickory Smoke solu contains as a hydrophobic material, hydrogenated vegetable tion, sold by Red Arrow Products Co. as CHARDEX oil. Advantageously, the hydrogenated vegetable oil is HICKORY. Other flavors contemplated by the invention present in the amounts of about 2-15% based upon total include those which impart a natural dry smoke flavor. These weight of formulation. include CHARZYME (a smoke flavor produced by combin 0094 For soft chewable formulations, all fillers (or dilu ing barley malt flour with an aqueous smoke flavor), CHAR ents) known in the soft chewable formulation art are contem plated. Non-limiting examples of fillers include Soy protein, MAIZE (a smoke flavor produced by combining yellow corn cob, or corn glutton meal. flower and an aqueous smoke flavor) and CHARSALT (a 0095 Preferred formulations are those containing about 5 blend of dendritic salt, aqueous Smoke flavor, and hydrated to 80% w/w of filler and especially preferred formulations are silicon dioxide. All of these flavors may be obtained by Red those containing about 10 to 70% w/w of filler. Arrow Products Co. The determination of the amounts of 0096 Advantageously, the soft chewable formulation flavor for a particular product is easily determined by a prac contains as a filler, soy protein fines. Advantageously, Soy titioner of this art. protein fines may be present in amounts of about 20% to 60% 0101 Advantageously, the soft chewable formulation based upon total weight of formulation. contains those flavors which provide a savory flavor. These 0097. For soft chewable formulations, flavors include flavors are well known to a practitioner of this art. Typical those known in pet foods which are artificial and include, for ranges are from 5-30% w/w. Advantageously, the flavor is a example: hickory smoke flavor or a beef flavor.

DRY GARLIC-ADE OS Formulated to provide a pungent garlic aroma. LIQUID GARLIC-ADE OS Same as dry garlic-ade in an oil miscible liquid form. LIQUID GARLIC-ADE Same as Dry Garlic-Ade but in a concentrated, oil CONCENTRATE OM miscible liquid form. DRY ONION-ADE Formulated to deliver an aroma and taste of cooked onions. DRY GARLICONION-ADE A dry blend of Garlic-Ade and Onion-Ade. DRY CHEESE-ADE Astrong cheddar cheese flavor and aroma. LIQUID CHEESE-ADE OM An oil miscible, liquid version of Dry Cheese-Ade. DRY CHICKEN-ADE Formulated to provide the aroma of baked chicken. LIQUID CHICKEN-ADE OS An oil soluble liquid version of Dry Chicken-Ade. LIQUID CHICKEN-ADE OS A concentrated form of Liquid Chicken-Ade OS. CONCENTRATE FFA DRY LIVER-ADE Formulated to provide the aroma and flavor of cooked liver. LIQUID LIVER-ADE A concentrated liquid version of Dry Liver-Ade. CONCENTRATE DRY PETADE BEEF STEW A blend of many flavor components which provide of beef Stew. LIQUID PETADE BEEF STEW OS An oil soluble, liquid version of Dry Pet-Ade Beef Stew. PETADE BEEF STEW A concentrated liquid version of Dry Pet-Ade Beef Stew. CONCENTRATE DRY BEEF-ADE A dry flavor formulated to provide the appeal of a baking roast. DRY FISH MEAL FLAVOR A dry flavor formulated to provide the odor of fish meal. CONCENTRATE LIQUID FISH MEAL FLAVOR A liquid version of Dry Fish Meal Flavor. CONCENTRATE DRYKANIN-KRAVE A spicy bone marrow flavor. DRY BACON-ADE A dry flavor which provides the aroma of frying bacon.

0098 Sources for these flavors are well-know to a practi 0102 For soft chewable formulations, all preservatives tioner in this art. For example, Kermine Petfood Nutrisurance known in the soft chewable formulation art are contemplated. is a vegetarian flavor for pet food is sold by Kemine indus Non-limiting examples include the parabens (methylparaben tries, Inc., Des Moines, IW. A discussion of commercial and/or propylparaben), benzalkonium chloride, benzetho Smoke flavorings is provided by Guillen et al. in J. Agr. and Food Chemistry vol. 4. nium chloride, benzoic acid, benzyl alcohol, bronopol, 0099 Preferred are the GRILLIN line of grill flavors and butylparaben, cetrimide, chlorhexidine, chlorobutanol, chlo blends marketed by the Red Arrow Products Company, LLC, rocresol, cresol, ethylparaben, imidurea, methylparaben, Manitowoc, Wis. for human and pet food. These include phenol, phenoxyethanol, phenylethyl alcohol, phenylmercu GRILLIN TYPECB-200, GRILLIN TYPESD, GRILLIN ric acetate, phenylmercuric borate, phenylmercuric nitrate, TYPE WS-50, GRILLIN TYPE CN, GRILLIN TYPECB, potassium Sorbate, sodium benzoate, sodium propionate, Sor GRILLIN TYPE GS and GRILLIN TYPE NBF. bic acid, thimerosal, propyl paraben, myristyl gama-pi 0100 Especially preferred are hickory smoked flavoring colinium chloride, paraben methyl, paraben propyl and qua produced by combining torula yeast and an aqueous hickory ternary ammonium compounds and the like. US 2008/01 60067 A1 Jul. 3, 2008

0103 Preferred formulations are those containing about ascorbate, Sodium metabisulfate, n-propyl gallate. BHA (bu 0.05 to 5% w/w of preservative and especially preferred for tylated hydroxy anisole), BHT (butylated hydroxy toluene) mulations are those containing about 0.1 to 2.5% w/w of monothioglycerol and the like, may be added to the present preservative. formulation. The antioxidants are generally added to the for 0104 Advantageously, the preservative is methylparaben mulation in amounts of from about 0.01 to about 2.0%, based and/or propylparaben. Advantageously, the preservative is upon total weight of the formulation, with about 0.1 to about Suitably used in the formulation in amounts ranging from 1.0% being especially preferred. about 0.01 to about 2.0% w/w, with about 0.2 to about 1.0% 0115 Granulating solvents are well known to those skilled w/w being especially preferred. in this art. Non-limiting examples of such solvents are water, 0105 For soft chewable formulations, all disintegrants aqueous Sorbitol Solution, etc. Other compounds which can known in the soft chewable formulation art are contemplated. act as solvents include polyethylene glycol 3350, glycerol Non-limiting examples include Sodium starch glycolate, caprylate/caprate and polyglycolized glycerides (GELU crospovidone, croScarmellose sodium, starch, micocrystal CIRE). line cellulose, alginic acid, Veegum, crospovidone, bentonite, 0116 Compounds which stabilize the pH of the formula and pregelatinized starch. tion (pH modifiers) are also contemplated. Again, such com 0106 Preferred formulations are those containing about pounds are well known to a practitioner in the art as well as 0.05 to 20% w/w of disintegrant and especially preferred how to use these compounds. Buffering systems include, for formulations are those containing about 1 to 12% w/w of example, systems selected from the group consisting of acetic disintegrant. Advantageously, the disintegrant is crospovi acid/acetate, malic acid/malate, citric acid/citrate, tataric done. acid/tartrate, lactic acid/lactate, phosphoric acid/phosphate, 0107 Advantageously, the disintegrant is suitably used in glycine/glycimate, tris, glutamic acid/glutamates and sodium the formulation in the amounts ranging from about 2-10% carbonate. Preferred ranges for pH include from about 4 to wfw. about 6.5. 0108 For soft chewable formulations, all humectants 0117. Other compounds contemplated by the inventive known in the soft chewable formulation art are contemplated. formulations include complexing agents, such as cyclodex Non-limiting examples include propylene glycol, glycerin, trins, PVP. PEG, ethyl lactate and niacinamide. Amounts of polyethylene glycol 400 and polyethylene glycol 3350. such compounds to be included in the inventive formulation 0109 Preferred formulations are those containing about are well known to a practitioner of the art. Also contemplated 0.01% to 20% w/w. are therapeutic agents to be in the form of emulsions, lipo 0110 Advantageously, the humectant is propylene glycol Somes or micelles. or purified water. Advantageously, these humectants may be 0118 Flow aids or glidants are also well known in the art present in amounts of about 2% to 20% based upon total and include, for example, silicon dioxide (CARBOSIL) or weight of formulation. silica gel (SYLOID), talc, starch, calcium, Stearate, magne 0111. The following chewable veterinary formulation is sium Stearate, and aluminum magnesium silicate (NEUSI most preferred: clindamycin HCl between 1 and 10%, hydro LIN). Amounts of flow aids are readily determined by a genated vegetable oil is between 2 and 15%, soy protein fines practitioner in this art and include for using about 0.01 to between 20-60%, flavor between 5-30%, preservative about 25%, based upon weight of total composition. Non between 0.2 to 1%, disintegrant between 2 and 10%, and limiting examples of lubricants for the tablets include mag propylene glycol, purified water, and other ingredients nesium and calcium Stearate and Stearic acid. Again, the vari between 2 and 20%. ous lubricants are well known to a practitioner of this art as 0112 Optionally, the chewable veterinary formulations well as the amounts of these compounds. Ranges include may also include lubricants, such as polyethylene glycols from about 0.01 to about 20% based upon the total weight of (PEG's or CARBOWAX), corn oil, mineral oil, hydrogenated formulation. vegetable oils (STEROTEX OR LUBRITAB), peanut oil, 0119 Further, the present invention provides for a method magnesium Stearate, soybean oil and/or castor oil. The inclu for enhancing the palatability of an oral Veterinary formula sion and identity of a lubricant is readily determined by a tion, which comprises including in the formulation a flavor practitioner of this art are present in amounts, for example, of that is liked by dogs. about 0.01 to about 20%, based upon total weight in the 0.120. This invention further provides for a process for composition. preparing a chewable veterinary formulation, which com 0113. Absorbents may also be added to the chewable vet prises the steps of erinary formulations. Such compounds are well known in the 0121 (a) blending the pharmaceutical agent, hydropho art to the practitioner as well as their use in pastes. These bic material, disintegrant, flavor, compounds effectively prevent or alleviate the phase separa 0.122 (b) adding the water, preservative, and the humec tion of the product during storage. Preferred absorbents tant to the mixture from step (a) and mixing the mixture; include magnesium carbonate, calcium carbonate, potassium and bicarbonate, Sodium bicarbonate, starch, cellulose and its 0123 (c) without drying, extruding the mixture. derivatives, or mixtures of absorbents, with magnesium car 0.124. In a second embodiment, the present invention pro bonate being especially preferred. The inclusion of these vides for a tablet veterinary formulation, which comprises an compounds is optional with amounts of 0% to about 30%. 0 to effective amount of therapeutic agent which comprises at about 15% or about 1% to about 15% or about 1% to about least one antibiotic, at least one filler, at least one disintegrant, 10%, based on total weight of the formulation being espe at least one binder, at least one product containing flavor, at cially preferred. least one colorant, and at least one granulating solvent. 0114 Antioxidants such as an alpha tocopheral, ascorbic 0.125 For tablet formulations, the antibiotic may be acid, ascrobyl palmitate, fumeric acid, malic acid, sodium selected from the following, which is to be considered non US 2008/01 60067 A1 Jul. 3, 2008

limiting: beta lactam, semisynthetic penicillins, bacitracin, 0.126 Preferred formulations are those containing about cephalosporins, quinolones, fluorinated quinolones, poly 0.01 to 50% w/w of therapeutic agent and especially preferred myxin, tetracyclines, chloramphenicol, macrollides, ami formulations are those containing about 2 to about 20% w/w noglycosides, nalidixic acid, rifamycins, and Sulfonamides. of therapeutic agent. I0127 Advantageously, the tablet formulation contains Some examples include amikacin, aminosalicyclic acid, clindamycin, or salts thereof. Most preferred is clindamycin amoxicillin, amoxicillin and clavulanate potassium, amplicil HCl in a range of 4-15% w/w. lin, azithromycin, bacampicillin, bacitracin, capreomycin, I0128. For tablet formulations, all fillers (or diluents) carbenicillin, carbenicillin indanyl Sodium, cefaclor, known in the tablet art are contemplated. Non-limiting cefadroxil, cefaloridine, cefamandole, cefazolin, cefazolin examples of fillers include anhydrous lactose, hydrated lac Sodium, cefepime, cefinetazole, cefixime, cefinetazole, cefo tose, sprayed dried lactose, crystalline maltose and maltodex dizime, cefonicid, cefoperaZone, ceforanide, cefotaxime, trins. cefotetan, cefoxitin, cefoxitin Sodium, cefpirome, cefpo I012.9 Advantageously, the tablet formulation contains as a doXime, cefpodoxime proxetil, cefiguinome, ceftaxidime, filler, lactose. Advantageously, the lactose may be present in ceftibuten, ceftiofur, ceftizoxime, ceftriaxone, cefuroxime, amounts of about 40% to 80% based upon total weight of cephacelor, cephadrine, cephalexin, cephalothin, cephaman formulation. dole, cephapirin, cepharadine, cephprozil, chloramphenicol, 0.130 Advantageously, the tablet formulation contains as a chlortetracycline, ciprofloxacin, clarithromycin, clindamy diluent, binder, carrier, filler, or as a flow enhancer, mannitol cin HCl, clindamycin or salts thereof, clindamycin phos in a range of 5-15% w/w. phate, clofazimine, cloxacillin, colistin, co-triamoxazole, 0131 For tablet formulations, all binders known in the cycloserine, dalfopristin, danofloxacin, demeclocycline, tabletart are contemplated. Non-limiting examples of binders dicloxacillin, difloxacin, dihydro-streptomycin, dirithromy include polyvinyl pyrrolidone, povidone, starch, pregelati cin, docycycline, efrotomycin, enoxacin, enrofloxacin, ertap nized starch, gelatin, methylcellulose, hydroxypropyl cellu enem, erythromycin and salts thereof, ethambutol HCl and lose, carboxymethyl cellulose Sodium, ethylcellulose, other salts, ethionamide, florfenicol, flumequine, fosfomycin, Sodium alginate, tragacanth, and acacia. fosfomycin, gamithromycin, gatifloxacin, gentamycin, imi I0132 Preferred formulations are those containing about 1 to 20% w/w of binder and especially preferred formulations penem, imipenemi-cilastin, isoniazid, kanamycin, levofloxa are those containing about 2-12% w/w of binder. cin, lincomycin, lineZolid, lomefloxacin, loracarbef 0.133 Advantageously, the tablet formulation contains, as mafenide, marbofloxacin, meropenem, methenamine, methi a binder, polyvinyl pyrrollidone. cillin, metronidazole, meZlocillin, minocycline, moxifloxa 0.134 Advantageously, the binder may be present in cin, nafcillin, nalidixic acid, neomycin, netilmicin, nitro amounts of about 3-10% w/w, depending on the selection, and furantoin, norfloxacin, novobiocin, ofloxacin, orbifloxacin, the amount, of disintegrant. ormetoprim, oxacillin, oxytetracycline, paromomycin, peni 0.135 For tablet formulations, all disintegrants known in cillin G, penicillin G aqueous, penicillin G benzatine, peni the tablet art are contemplated. Non-limiting examples of cillin G procaine, penicillinV, penicillinV penicillin salts and disintegrants include sodium starch glycolate, crospovidone, complexes, pentamidine, piperacillin, piperacillin Sodium, croScarmellose sodium, Starch, micocrystalline cellulose, piperacillin-taZobactam, polymixin B. pyrazinamide, alginic acid, veegum, crospovidone, bentonite, and pregela rifampin, roxithromycin, salts of carbenicillin, silver sulfadi tinized starch. azine, sparfloxacin, spectinomycin, spiramycin, Streptomy 0.136 Preferred formulations are those containing about 1 cin, Streptozocin, Sufadimethoxine-ormetoprim, Sulfaceta to 20% w/w of disintegrant and especially preferred formu mide, Sulfacytine, Sulfadiazine, Sulfadimethoxine, lations are those containing about 2-12% w/w of disintegrant. Sulfadimethoxine-trimethoprim, Sulfamerazine, Sulfamet 0.137 Advantageously, the tablet formulation contains as a hazine, Sulfamethixole, Sulfapyridine, Sulfapyrizine, Sul disintegrant, crospovidone. fasalazine, Sulfinethoxazole, Sulfisoxazole, taZobactam, 0.138 Advantageously, the disintegrant may be present in teicoplanin, tetracycline, tetracycline HCl, tiamulin, ticarcil amounts of about 3-10% w/w, depending on the selection, and lin, ticarcillin and clavulanate potassium, tilmicosin, tobra therefore the amount, of binder. mycin, trimethoprim, trimetrexate and ketolides, troleano 0.139. For tablet formulations, all flavors known in pet mycin, trovafloxacin, tulathromycin, tylosin, Vancomycin foods, which are artificial, are contemplated and include, for and ketolides such as tellithromycin and HMR 3004. example:

DRY GARLIC-ADE OS Formulated to provide a pungent garlic aroma. LIQUID GARLIC-ADE OS Same as dry garlic-ade in an oil miscible liquid form. LIQUID GARLIC-ADE Same as Dry Garlic-Ade but in a concentrated, oil CONCENTRATE OM miscible liquid form. DRY ONION-ADE Formulated to deliver an aroma and taste of cooked onions. DRY GARLICONION-ADE A dry blend of Garlic-Ade and Onion-Ade. DRY CHEESE-ADE A strong cheddar cheese flavor and aroma. LIQUID CHEESE-ADE OM An oil miscible, liquid version of Dry Cheese-Ade. DRY CHICKEN-ADE Formulated to provide the aroma of baked chicken. LIQUID CHICKEN-ADE OS An oil soluble liquid version of Dry Chicken-Ade. LIQUID CHICKEN-ADE OS A concentrated form of Liquid Chicken-Ade OS. CONCENTRATEFFA US 2008/01 60067 A1 Jul. 3, 2008 11

-continued DRY LIVER-ADE Formulated to provide the aroma and flavor of cooked liver. LIQUID LIVER-ADE A concentrated liquid version of Dry Liver-Ade. CONCENTRATE DRY PETADE BEEF STEW A blend of many flavor components which provide of beef Stew. LIQUID PETADE BEEF STEW OS An oil soluble, liquid version of Dry Pet-Ade Beef Stew. PETADE BEEF STEW A concentrated liquid version of Dry Pet-Ade Beef Stew. CONCENTRATE DRY BEEF-ADE A dry flavor formulated to provide the appeal of a baking roast. DRY FISH MEAL FLAVOR A dry flavor formulated to provide the odor of fish meal. CONCENTRATE LIQUID FISH MEAL FLAVOR A liquid version of Dry Fish Meal Flavor. CONCENTRATE DRYKANIN-KRAVE A spicy bone marrow flavor. DRY BACON-ADE A dry flavor which provides the aroma of frying bacon.

0140 Sources for these flavors are well-know to a practi preferred are organic dyes and titanium dioxide. Preferred tioner in this art. For example, Kermine Petfood Nutrisurance ranges include from about 0.5% to about 25% based upon is a vegetarian flavor for pet food is sold by Kemine indus total weight of formulation. tries, Inc., Des Moines, IW. A discussion of commercial 0146 For tablet formulations, water is added, q.S. to Smoke flavorings is provided by Guillen et al. in J. Agr. and 100%. Food Chemistry vol. 4. 0147 The following tablet formulation is most preferred: 0141 Preferred are the GRILLIN line of grill flavors and clindamycin HCl between 4 and 15%, lactose carrier between blends marketed by the Red Arrow Products Company, LLC, 40 and 80%, mannitol between 5 and 15%, binder and disin tegrant between 3 and 10%, flavor between 10 and 20%, color Manitowoc, Wis. for human and pet food. These include between 0.1 and 0.5%, and purified water and other ingredi GRILLIN TYPE CB-200, GRILLINTYPE SD, GRILLIN ents qs. 100%. TYPE WS-50, GRILLIN TYPE CN, GRILLIN TYPECB, 0.148. Optionally, the tablet formulations of the present GRILLINTYPE GS and GRILLIN TYPE NBF. invention may further contain other inert ingredients such as 0142. Especially preferred are hickory smoked flavoring absorbents, antioxidants, granulating solvents, stabilizers or produced by combining torula yeast and an aqueous hickory Surfactants. These compounds are well known in the formu smoke solution, sold by Red Arrow Products Co. as CHAR lation art. TOR HICKORY or a hickory smoke flavoring produced by 0149 Absorbents may also be added to the inventive for combining maltodextin with an aqueous hickory Smoke solu mulations. Such compounds are well known in the art to the tion, sold by Red Arrow Products Co. as CHARDEX practitioner as well as their use in pastes. These compounds HICKORY. Other flavors contemplated by the invention effectively prevent or alleviate the phase separation of the include those which impart a natural dry smoke flavor. These product during storage. Preferred absorbents include magne include CHARZYME (a smoke flavor produced by combin sium carbonate, calcium carbonate, potassium bicarbonate, ing barley malt flour with an aqueous smoke flavor), CHAR Sodium bicarbonate, starch, cellulose and its derivatives, or MAIZE (a smoke flavor produced by combining yellow mixtures of absorbents, with magnesium carbonate being flower and an aqueous smoke flavor) and CHARSALT (a especially preferred. The inclusion of these compounds is blend of dendritic salt, aqueous Smoke flavor, and hydrated optional with amounts of 0% to about 30%. 0 to about 15% or silicon dioxide. All of these flavors may be obtained by Red about 1% to about 15% or about 1% to about 10%, based on Arrow Products Co. total weight of the formulation being especially preferred. 0143. The determination of the amounts of flavor for a 0150 Antioxidants such as an alpha tocopheral, ascorbic particular product is easily determined by a practitioner of acid, ascrobyl palmitate, fumeric acid, malic acid, sodium this art. Preferred are those flavors which provide a savory ascorbate, Sodium metabisulfate, n-propyl gallate. BHA (bu flavor. These flavors are well known to a practitioner of this tylated hydroxy anisole), BHT (butylated hydroxy toluene) art monothioglycerol and the like, may be added to the present 0144. Advantageously, the tablet formulation contains formulation. The antioxidants are generally added to the for those flavors which provide a savory flavor. These flavors are mulation in amounts of from about 0.01 to about 2.0% w/w, well known to a practitioner of this art. Typical ranges are with about 0.1 to about 1.0% w/w being especially preferred. from 5-30% w/w. Advantageously, the tablet formulation 0151. Granulating solvents are well known to those skilled contains a hickory smoke flavor or a beef flavor. Advanta in this art. Non-limiting examples of such solvents are water, geously, flavor is added between 10 and 20% based upon total aqueous Sorbitol Solution, etc. Other compounds which can weight of formulation. act as solvents include polyethylene glycol 3350, glycerol 0145 For tablet formulations, all colorants known in the caprylate/caprate and polyglycolized glycerides (GELU tablet art are contemplated. Non-limiting examples include, CIRE). but are not limited to, dyes, an aluminum lake, caramel 0152 Compounds which stabilize the pH of the formula (which may also function as a flavor), colorant based upon tion (pH modifiers) are also contemplated. Again, such com iron oxide or a mixture of any of the foregoing. Especially pounds are well known to a practitioner in the art as well as US 2008/01 60067 A1 Jul. 3, 2008 how to use these compounds. Buffering systems include, for bacitracin, capreomycin, carbenicillin, carbenicillin indanyl example, Systems selected from the group consisting of acetic Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, acid/acetate, malic acid/malate, citric acid/citrate, tataric cefazolin, cefazolin sodium, cefepime, cefinetazole, acid/tartrate, lactic acid/lactate, phosphoric acid/phosphate, cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, glycine/glycimate, tris, glutamic acid/glutamates and sodium ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin carbonate. Preferred ranges for pH include from about 4 to Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, about 6.5. cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, 0153. Other compounds contemplated by the inventive ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, formulations include complexing agents, such as cyclodex cephalothin, cephamandole, cephapirin, cepharadine, ceph trins, PVP. PEG, ethyl lactate and niacinamide. Amounts of prozil, chloramphenicol, chlortetracycline, ciprofloxacin, such compounds to be included in the inventive formulation clarithromycin, clindamycin HCl, clindamycin or salts are well known to a practitioner of the art. Also contemplated thereof, clindamycin phosphate, clofazimine, cloxacillin, are therapeutic agents to be in the form of emulsions, lipo colistin, co-triamoxazole, cycloserine, dalfopristin, danof Somes or micelles. loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro 0154 Flow aids or glidants are also well known in the art streptomycin, dirithromycin, docycycline, efrotomycin, and include, for example, silicon dioxide (CARBOSIL) or enoxacin, enrofloxacin, ertapenem, erythromycin and salts silica gel (SYLOID), talc, starch, calcium, Stearate, magne thereof, ethambutol HCl and other salts, ethionamide, flo sium Stearate, and aluminum magnesium silicate (NEUSI rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy LIN). Amounts of flow aids are readily determined by a cin, gatifloxacin, gentamycin, imipenem, imipenemi-cilastin, practitioner in this art and include for using about 0.01 to isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, about 25%, based upon weight of total composition. Non lomefloxacin, loracarbef mafenide, marbofloxacin, mero limiting examples of lubricants for the tablets include mag penem, methenamine, methicillin, metronidazole, mezlocil nesium and calcium Stearate and Stearic acid. Again, the Vari lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo ous lubricants are well known to a practitioner of this art as mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, well as the amounts of these compounds. Ranges include ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy from about 0.01 to about 20% based upon total weight of cline, paromomycin, penicillin G, penicillin Gaqueous, peni formulation. cillin G benzatine, penicillin G procaine, penicillin V, peni O155 Moreover, in an alternative embodiment this inven cillin V penicillin salts and complexes, pentamidine, tion provides for tablets which are coated. The inventive piperacillin, piperacillin sodium, piperacillin-taZobactam, tablets are prepared according to methods conventional in the polymixin B. pyrazinamide, rifampin, roXithromycin, salts of art, Such as wet and dry granulation processes. The chewable carbenicillin, silver Sulfadiazine, sparfloxacin, spectinomy formulations and tablets provided for by this invention may cin, spiramycin, Streptomycin, Streptozocin, Sufadimethox be coated using techniques conventional in the art. Coatings ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, for chewables Veterinary formulations include gelatin, glyc Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam eryl behenate, coca butter, and beeswax. Other coatings erazine, Sulfamethazine, Sulfamethixole, Sulfapyridine, Sul would be known to a practitioner in this art. Coatings for fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, tablets include Sugar coatings, such as seal coatings, Subcoat taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia ings, and syrup coatings, as well as film coatings, such as mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi pan-pour coatings and pan spray coatings. As well known to cosin, tobramycin, trimethoprim, trimetrexate and ketolides, a practitioner of this art, the coatings contain additional com troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco ponents such as solvents, plasticizers, colorants, opaquant mycin and ketolides such as tellithromycin and HMR 3004. extenders and film formers. 0160 Preferred formulations are those containing about 1 0156. Often it is beneficial to administer a formulation that to 50% w/v of therapeutic agent and especially preferred contains a combination of two or more antibiotics, which formulations are those containing about 8 to about 20% w/v. possess different activity, in order to obtain a composition of therapeutic agent. with a broad spectrum of activity. The inventive oral formu 0.161 Advantageously, the long-acting injectable formu lations herein described may be used to co-administer more lation contains clindamycin, or salts thereof. Most preferred than one antibiotic. is clindamycin HCl in a range of 9-18% w/v. 0157. The inventive tablet formulations are prepared 0162 The poloxamer may be selected from the following: according to methods conventional in the art, Such as wet and ..alpha.-Hydro-omega.-hydroxypoly(oxyethylene)poly(OX dry granulation processes. ypropylene)poly(oxyethylene) block copolymer, 1.2-Propy 0158. In a third embodiment, the present invention pro leneglycol, ethoxylated and propoxylated, 106392-12-5, vides for a long-acting injectable (LAI) formulation, which 11104-97-5, 53637-25-5, 60407-69-4, 65187-10-2, 69070 comprises at least one therapeutic agent which comprises at 95–7, 75-H-1400, 75H90000, 9003-11-6, Adeka 25R1, least one antibiotic, at least one polxamer, and at least one Adeka 25R2, Adeka L 61, Adeka Pluronic F 108, AIDS aqueous solvent. 162017, AIDS162017, alpha-Hydro-omega-hydroxypoly 0159. The antibiotic may be selected from the following, (oxyethylene) (Sub a)-poly(Oxopropylene)(Sub b)-poly(oxy which is to be considered non-limiting: beta lactam, semisyn ethylene)(Sub a) block copolymer, alpha-Hydro-omega thetic penicillins, bacitracin, cephalosporins, quinolones, flu hydroxypoly(oxyethylene)a-poly(Oxopropylene)b-poly orinated quinolones, polymyxin, tetracyclines, chloram (oxyethylene)a block copolymer, Antarox 17R4, Antarox phenicol, macrollides, aminoglycosides, nalidixic acid, 25R2, Antarox B 25, Antarox F 108, Antarox F 68, Antarox F rifamycins, and Sulfonamides. Some examples include Ami 88, Antarox F 88FL, Antarox L 61, Antarox L 72, Antarox P kacin, aminosalicyclic acid, amoxicillin, amoxicillin and cla 104, Antarox P 84, Antarox SC 138, Arco Polyol R 2633, Vulanate potassium, amplicillin, azithromycin, bacampicillin, Arcol E 351, B 053, BASF-L 101, Berol TVM370, Bloat US 2008/01 60067 A1 Jul. 3, 2008 guard, Block polyethylene-polypropylene glycol, Block ethoxylated propylene glycol, Polypropylene glycol, polyoxyethylene-polyoxypropylene, Breox BL 19-10, BSP ethoxylated, Polypropylene glycol-ethylene oxide copoly 5000, C13430, Cirrasol ALN-WS, component of Casakol, mer, PPG Diol 3000EO, Proksanol, Pronon, Pronon102, component of Epitrate, Crisvon Assistor SD 14, CRL 1005, Pronon104, Pronon201, Pronon204, Pronon 208, Propane-1, CRL 1605, CRL 8131, CRL 8142, D 500 (polyglycol), Dal 2-diol, ethoxylated, propoxylated, Propylen M12. Propylene tocel F 460, Dehypon KE 3557, Detalan, Eban 710, Emkalyx glycol, propylene oxide, ethylene oxide polymer, Propylene EP 64, Emkalyx L 101, Emkalyx L101, Empilan P 7068, oxide-ethylene oxide copolymer, Propylene oxide-ethylene Emulgen PP230, Epan 450, Epan 485, Epan 710, Epan 750, oxide polymer, Proxanol, Proxanol 158, Proxanol 228, Prox Epan 785, Epan U 108, Epon 420, Ethylene glycol-propylene anol Tsl-3, RC 102, Regulaid, Rokopol 16P, Rokopol 30P. glycol block copolymer, Ethylene glycol-propylene glycol Rokopol 30P9, SK and F 18,667, SK&F 18,667, SKandF 18,667, Slovanik, Slovanik 630, Slovanik 660, Slovanik polymer, ETHYLENE OXIDE, PROPYLENE OXIDE M-640, Supronic B 75, Supronic E 400, Symperonic PE BLOCK POLYMER, Ethylene oxide-propylene oxide block 30/40, Tergitol monionic XH, Tergitol nonionic XH, Tergitol copolymer dipropylene glycol ether, Ethylene oxide-propy XH, Tergitol XH (nonionic), Teric PE 61, Teric PE 62, Teric lene oxide block copolymer ether with ethylene glycol, Eth PE40, Teric PE60, Teric PE70, Thanol E 4003, Therabloat, ylene oxide-propylene oxide block polymer, Ethylene oxide TsL 431, TVM 370, Unilube 50 MB168X, Unilube 50 propylene oxide copolymer, F 108, F 127, F 77, F 87, F 88, MB26X, Velvetol OE2NT1, Voranol P 2001, WS 661, Wyan F-108, Genapol PF 10, Glycols, polyethylene-polypropy dotte 7135. lene, Glycols, polyethylenepolypropylene, HSDB 7222, 0163 Preferred formulations are those containing about 1 Hydrowet, Laprol 1502, LG 56, Lutrol F. Lutrol F (TN), M to 50% w/v of poloxamer and especially preferred formula 90/20, Magcyl, Meroxapol 105, Methyloxirane polymer with tions are those containing about 5 to about 40% w/v of polox oxirane block, Methyloxirane-oxirane copolymer, Methylox amer. Advantageously, the poloxamer is LUTROL(R) F 127 irane-oxirane polymer, Monolan 8000E80, Monolan PB, N and LUTROL(R) F 68 and is suitably used in the formulation in 480, Newpol PE-88, Niax 16-46, Niax LG56, Nissan Pronon the amounts ranging from about 10-30% w/v. 201, Nixolen SL 19, NSC 63908, NSC63908, Oligoether 0164. Most preferred is a LAI formulation, which com L-1502-2-30. Oxirane, methyl-, polymer with oxirane, prises: clindamycin phosphate between 9 and 18%, Oxirane, methyl-, polymer with oxirane, block, Oxirane, LUTROL(R) between 5 and 30%, and sterile water for injec methyl-, polymer with oxirane, ether with 1,2-propanediol tion q. s. 100%. (2:1). Oxirane, polymer with methyloxirane, Oxirane-methy 0.165. The long-acting injectable formulation of the loxirane polymer, P 103, P 104, P 105, P123, P65, P84, P85, present invention may be prepared by adding the therapeutic PEG/PPG-125/30 Copolymer, Plonon 201, Plonon 204, Plu agent with the poloxamerand mixing until uniform. Since the racare, Pluracol V. Pluriol PE, Pluriol PE 6810, Pluronic, long acting formulation is intended for injection, it is neces Pluronic 10R8, Pluronic 31R2, Pluronic C 121, Pluronic F. sary that it be sterilized. Heat sterilization is generally to be Pluronic F 108, Pluronic F 125, Pluronic F 127, Pluronic F38, avoided in the situation where the therapeutic agent is Pluronic F 68, Pluronic F 68LF, Pluronic F87, Pluronic F 88, unstable at autoclave temperatures. Rather, membrane steril Pluronic F98, Pluronic F-68, Pluronic F108, Pluronic F127, ization is preferred in those situations. The sterile mixture is Pluronic F68, Pluronic F77, Pluronic F86, Pluronic F87, Plu further mixed with sterile water for injection, q.s. to 100%. ronic F87-A7850, Pluronic F88, Pluronic L, Pluronic L 101, 0166 In an alternative embodiment, the long-acting Pluronic L 121, Pluronic L 122, Pluronic L 24, Pluronic L31, injectable veterinary formulation comprises the steps of Pluronic L35, Pluronic L 44, Pluronic L 61, Pluronic L. 62, Pluronic L 64, Pluronic L 68, Pluronic L92, Pluronic L-101, 0.167 (a) stirring the poloxamer into purified water at 5° Pluronic L-81, Pluronic 144, Pluronic L62, Pluronic 162 (mw C.; 2500), Pluronic L64, Pluronic 164 (mw 2900), Pluronic P. 0168 (b) optionally adding a second poloxamer to the Pluronic P 104, Pluronic P 75, Pluronic P85, Pluronic P-65, mixture from step (a) and mixing the mixture; and Pluronic P-75, Pluronic P103, Pluronic P104, Pluronic P105, 0.169 (c) optionally adding a polyacrylic acid into an Pluronic P123, Pluronic P65, Pluronic P84, Pluronic P85, aliquot of water, and completely hydrating the poly Pluronic-68, Poloxalene, Poloxalene L64, Poloxalene acrylic acid before mixing it into the poloxamer Solution USAN:BAN:INN, Poloxalkol, Poloxamer, Poloxamer 101, at 5° C.; Poloxamer 108, Poloxamer 182LF, Poloxamer 188, Polox 0170 (d) neutralizing the Carbopol using triethanola amer 331, Poloxamer 407, Poloxamer USAN:BAN:INN, mine. Poloxamer-188, Poly (propylene oxide-ethylene oxide), Poly 0171 (e) dissolving the drug in ethanol/propylene gly (ethylene oxide-co-propylene oxide), Poly(mixed ethylene, col and adding it to the above Solution. propylene)glycol, Poly(oxyethylene)-poly(oxypropylene) 0172. In an alternative embodiment, the long-acting glycol, Poly(Oxyethylene)-poly(oxypropylene) polymer, injectable veterinary formulation comprises the steps of Polyethylene glycol, propoxylated, Polyethylene oxide (0173 (a) dissolving LUTROL(R) F 127 completely in polypropylene oxide, Polyethylene oxide-polypropylene water at room temperature or water pre-cooled to oxide copolymer, Polyethylene-Pluronic L-62LF, Polyethyl approximately 5° C. ene-polypropylene glycol, Polykol, Polylon 13-5, Polyox 0.174 (b) dissolving active substances that are insoluble amer 108, Polyoxyethylenated poly (oxypropylene), Poly in water, in ethanol, isopropanol or propylene glycol oxyethylene-polyoxypropylene block copolymer, 0.175 (c) mixing the therapeutic agent solution with the Polyoxyethylene-polyoxypropylene copolymer, Polyoxyeth aqueous phase at 5° C. to form a homogeneous mass. ylene polyoxypropylene, Polyoxyethylene-oxy-propylene 0176). In an alternative embodiment, the long-acting French, Polyoxyethylene-polyoxypropylene, Polyoxyeth injectable veterinary formulation comprises the steps of ylene-polyoxypropylene polymer, Polyoxypropylene-poly (0177) (a) dissolving LUTROL(R) F 127 in water at room oxyethylene block copolymer, Polypropoxylated, poly temperature at approximately 70° C. US 2008/01 60067 A1 Jul. 3, 2008

0.178 (b) dissolving active substances that are insoluble 0186 Pharmacokinetic analysis was performed using in water, in ethanol, isopropanol or propylene glycol at WinNonlin software, version 4.0 (Pharsight Corporation, 700 C. Mountain View, Calif., 2002). The area under the plasma 0179 (c) mixing the therapeutic agent solution with the concentration-time curve (AUC) was calculated using the warm aqueous phase to form a homogeneous mass. linear/logarithmic trapezoidal method from 0 to the last point 0180. The inventive formulations herein described may be at which drug concentration was quantified AUC(0-t). used to treat a number of disease states by administering to the Clearance and volume of distribution values, not corrected for host in need thereof an effective amount of the formulation bioavailability, were also calculated for each animal. The containing the pharmaceutical agent. The determining of a terminal elimination halflife was calculated via linear regres treatment protocol of a specific indication would be well sion of the last two to four nonzero values. C, and T for within the skill level of a practitioner in the pharmaceutical or each animal were taken as the highest observed concentration Veterinary arts. The hosts include all animals, e.g. cats, dogs, and time to that observation. cattle, sheep, horses, and pigs. TABLE 1 0181. The inventive formulations herein described may be Summary of pharmacokinetic parameters for a capsule administered to a warm-blooded animals, such as cattle, (ANTIROBE), soft chewable, or hard chewable at sheep, pigs, cats, dogs, horses, llamas, deer, rabbits, skunks, 10 mg/kg (nominal) clindamycinto dogs raccoons, camels and the like, or birds. The amount of phar Soft chew Hard chew maceutical active agent depends on the individual therapeutic Antirobe Avgi SD Avgi SD agent, the animal being treated, the disease state, and the Avgi SD (n = 10) (n = 10) (n = 10) severity of the disease state. The determination of those fac AUC(O-ta) 174OO 10400 183OO 9410 173OO 10300 tors is well within the skill level of the practitioner. (ng hr/mL) Cmax 372O 1380 3.070981 3640 1060 EXAMPLES (ng/mL) Tmax 1.25 O.72 1.55 - 0.80 1.10 - 0.32 Example 1 (hr) T12 (hr) S.O2 2.26 S.7S 4.65 6.97 6.82 Tablet and Soft Chewable Formulations Demonstrate VF (mL/kg) 47OO 2760 4340 - 3640 S800, S330 Comparable Bioavailability to a Conventional Cap CIF (mL/hrikg) 678 - 341 644,393 740 - 498 sule Product Arithmetic averages; Values rounded to 3 significant digits: 0182 Six healthy Beagle or mongrel dogs, 6.3 to 15.0 AUC = Area. Under the Curve: C ax = Peak Concentration; months of age, weighing 7.8 to 10.0 kg were studied in this T = Time to Peak Concentration; randomized, five-period crossover study. Dogs were ran T2 = terminal elimination half life; domly assigned to one of three treatment sequences by lot VF = apparent volume of distribution (not corrected for bioavailability); tery. Within each sequence, dogs received one of three treat CL/F = clearance (not corrected for bioavailability) ments on Days 0, 7, 14, 21 and 28. On each treatment day, dogs received either clindamycin capsules (Group 1), soft Example 2 chewables (Group 2) or chewable tablets (Group 3). All treat ments were administered orally at a dose rate of at least 10 Preferred Soft Chewable Formulation mg/kg. 0187 Table 2 provides the preferred concentrations of 0183 Blood samples were collected prior to each treat active ingredient and excipients for soft chewable formula ment and at 0.5, 1, 1.5, 3, 6, 12 and 24 hours after each tions. treatment. FIG. 1 provides plasma concentration levels (ng/ TABLE 2 ml) of clindamycin at each time point. The results indicate that the mean concentration-time profiles were parallel, with i Ingredient % the mean Cmax slightly higher for the commercial product, 1 Clindamycin HCI 1-5% ANTIROBE. 2 Hydrogenated vegetable Oil 2-15% 3 Soy Protein Fines 20-60% 0184 The pharmacokinetic parameters among the three 4 Flavor S-30% treatment groups were similar with average terminal half lives 5 Preservative O.2-1.0% of 5-7 hr and average times to maximum concentration of 6 Disintegrant 2-10% 1.1-1.6 hr. The relative bioavailabilities of the soft and hard 7 Propylene Glycol/Purified wateriother 2-20% chews are 87 and 110% w/v. respectively compared to ANTI ingredients ROBE. Additionally, the pharmacokinetic parameters were broadly similar between groups fed 1.5-3 hour post dose versus 6 hours post dose for all formulations. Example 3 Analysis of Plasma Concentration of Clindamycin Preferred Tablet Formulation 0188 Table 3 provides the preferred concentrations of 0185. A bioanalytical method for the determination of active ingredient and excipients for tablet formulations. clindamycin from canine serum samples was developed using TABLE 3 Reversed-Phase HPLC with UV Detection. All serum samples were extracted using a liquid-liquid extraction pro i Ingredient % (w.fw) cedure and injected on an HPLC with UV absorption at 210 1 Clindamycin HCl 4-15% nm. Sets offortified control samples to assess method perfor 2 Lactose Carrier 40-80% mance, along with an unfortified control sample were 3 Mannitol S-15% included to assess any inherent interference. US 2008/01 60067 A1 Jul. 3, 2008 15

(0197) Gel Preparation Method 3: “Hot Process” TABLE 3-continued 0198 LUTROL(R) F 127 will be dissolved in water at approximately 70° C. Active substances that are insoluble in i Ingredient % (w.fw) water will be dissolved in ethanol, isopropanol or propylene 4 Binder and disintegrant 3-10% glycol at 70° C. and mixed with the warm aqueous phase to 5 Flavor 10-20% form a homogeneous mass. The gel will form when the solu 6 Color O.1-0.5% tion cools to room temperature. 7 Purified wateriother ingredients Qs. 100% 0199 Rheology: Using a rotation viscosimeter equipped with a probe the thermorheological behavior will be mea sured by adjusting a temperature interval from 0-90° C. with Example 4 a ramp of 1° C. per minute. The rotation speed will be kept constant at 250 rpm. The rheological studies will be examined Preferred Long-Acting Injectable Formulation at a temperature of 40°C. using a shear rate from 0-65-0 rpm 0189 Table 4 provides the preferred concentrations of within 120 s. active ingredient and excipients for long-acting injectable 0200 Gel strength: The resistance to penetration of the formulations. gels at 40° C. will be performed by means of a software controlled penetrometer with a 5 kg load cell and a 20 mm probe. The pre-test speed will be adjusted at 5 mm/s and the TABLE 4 test speed will be 1 mm/s. The chosen penetration depth will Clindamycin Phosphate 9-18% be 5 mm. LUTROL (RF 127 or LUTROL (RF 127 and S-30% F 68 0201 Thermorheological properties: The addition of Sterile water for injection Qs. 100% LUTROL(R) F 68 is expected to strongly influence the ther morheological properties of F 127 formulations. In contrast to the effect of common used salts (e.g. NaCl) the addition of 0190. Various kinds of LUTROL(R) are available for use in LUTROLOR F 68 to LUTROLR) F 127 formulations is the LAI formulation. In the present example, preferred polox expected to result in an increase of the Sol-gel-transition amers were LUTROL(R) F 127 (poloxamer 407) and F 68 temperature. At constant amounts of LUTROL(R) F 68 the (poloxamer 188). LUTROL(R) F 127 is soluble in water, etha thermoreversible gelling temperature can be adjusted by nol (95%) and isopropanol. It is used primarily as a thicken varying the LUTROL(R) F 127 concentration. ing agent and gel former. In particular, LUTROL(R) F 127 is 0202 The addition of small amounts of PAA as bioadhe suitable for the formulation of active substances that show sive polymer is expected to lead to a further decrease of the reduced solubility as a result of neutralization. Owing to its gelling temperature of the LUTROL(R) F 127/F 68 combina ability to affect viscosity, LUTROL(R) F 127 is suitable as a tions. stabilizer for topically and orally administered Suspensions. 0203 Viscosity: A considerable increase of the viscosity is (0191). LUTROL(R) F 68 is readily soluble in water. It is expected to be observed with rising amounts of LUTROL(R) F primarily applied as an emulsifier, Solubilizer, and Suspension 68. At high concentrations of LUTROL(R) F 68 a sharp gelling stabilizer in liquid oral, topical and parenteral dosage forms. temperature and a strong viscosity increase is expected. The It is particularly useful for enhancing the solubility and bio viscosity of the gel form is expected to be higher when small availability of sparingly water Soluble active drugs. quantities of PAA are present. With increasing amount of LUTROL(R) F 68 has a low toxicity profile with minimal side PAA these effects are expected to be reinforced. The influence effects. of the different F 127/F 68 combinations and the addition of (0192. In the present example, LUTROL(R) F 127 and F 68 PAA on the viscosity of the gels will be confirmed by pen may be used in combination. When LUTROL(R) F 68 is used etration resistance measurements. in combination with a gel-forming poloxamer, like 0204 Therapeutic Agent: The choice of therapeutic agent LUTROL(R) F 127, it strongly influences the thermorheologi is expected to strongly influence the properties of the cal properties of F127 preparations, resulting in an increase of LUTROL(R) F 127/F 68 mixtures by lowering the gelling the sol-gel transition temperature. At constant amounts of F temperature. The required amount of LUTROL F 127 will 127, the viscosity and thermo-reversible gelling temperature have to be adapted. are functions of the LUTROLR) F 68 concentration. (0205 The viscosity of Lutrol F 127 gels may be affected (0193 Gel Preparation Method 1: by the addition of electrolytes, moisturizers, alcohols and (0194 LUTROL(R) F 127 will be stirred into purified water surfactants. Thus, the addition of more than 1% sodium chlo at 5° C. and LUTROLR) F 68 will be added. For the bioadhe ride will reduce the gel formation temperature as well as the sive formulations, a polyacrylic acid (PAA) will be dispersed Viscosity and pour point. Similar effects are also seen with into an aliquot of water, completely hydrated, and mixed with potassium chloride. In contrast to this, ethanol will increase the LUTROL(R) solution at 5° C. The Carbopol will be neu the gel formation temperature. The use of anionic Surfactants tralized using triethanolamine. The drug will be dissolved in may inhibit gel formation, even at Lutrol F 127 concentra ethanol/propylene glycol and the Solution added. tions of over 20%. This is true, for example, for sodium lauryl (0195 Gel Preparation Method 2: “Cold Process” sulphate at concentrations above 2%. Low pH values affect (0196. LUTROL(R) F 127 will be dissolved completely in both the gel formation temperature and the Viscosity. water at room temperature or water pre-cooled to approxi 0206. The invention is further described by the following mately 5°C. Active substances that are insoluble in water will numbered paragraphs: be dissolved in ethanol, isopropanol or propylene glycol and 1. A chewable antibiotic formulation comprising an antibi mixed with the aqueous phase at 5°C. to form a homogeneous otic, hydrophobic material, a filler, a disintegrant, a solvent, a SS. and optionally a flavor, and optionally a preservative. US 2008/01 60067 A1 Jul. 3, 2008

2. The formulation according to paragraph 1 wherein the 8. The formulation according to paragraph 2 where in the antibiotic is between 1 and 5% of the formulation, the hydro filler is soy protein. phobic material is between 2 and 15%, the filler is between 9. The formulation according to paragraph 2 wherein the 20-60%, the flavor is between 5-30%, the preservative is flavor is a hickory smoke flavor or a beef flavor. between 0.2 to 1%, the disintegrant is between 2 and 10%, and 10. The formulation according to paragraph 2 wherein the the humectant is between 2 and 20%. preservative is selected from the group consisting of parabens 3. The formulation according to paragraph 2 wherein the (methylparaben and/or propylparaben), benzalkonium chlo antibiotic is selected from the group consisting of amikacin, ride, benzethonium chloride, benzoic acid, benzyl alcohol, aminosalicyclic acid, amoxicillin, amoxicillin and clavulan bronopol, butylparaben, cetrimide, chlorhexidine, chlorobu ate potassium, amplicillin, azithromycin, bacampicillin, baci tanol, chlorocresol, cresol, ethylparaben, imidurea, meth tracin, capreomycin, carbenicillin, carbenicillin indanyl ylparaben, phenol, phenoxyethanol, phenylethyl alcohol, Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, phenylmercuric acetate, phenylmercuric borate, phenylmer cefazolin, cefazolin Sodium, cefepime, cefinetazole, curic nitrate, potassium Sorbate, Sodium benzoate, sodium cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, propionate, Sorbic acid, thimerosal, propyl paraben, myristyl ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin gama-picolinium chloride, paraben methyl, paraben propyl Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, and quaternary ammonium compounds. cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, 11. The formulation according to paragraph 2 wherein the ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, preservative is methylparaben and/or propylparaben. cephalothin, cephamandole, cephapirin, cepharadine, ceph 12. The formulation according to paragraph 2 wherein the prozil, chloramphenicol, chlortetracycline, ciprofloxacin, disintegrant is selected from the group consisting of sodium clarithromycin, clindamycin HCl, clindamycin or salts starch glycolate, crospovidone, croscarmellose Sodium, thereof, clindamycin phosphate, clofazimine, cloxacillin, starch, micocrystalline cellulose, alginic acid, veegum, colistin, co-triamoxazole, cycloserine, dalfopristin, danof crospovidone, bentonite, and pregelatinized starch. loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro 13. The formulation according to paragraph 2 wherein the streptomycin, dirithromycin, docycycline, efrotomycin, disintegrant is crospovidone. enoxacin, enrofloxacin, ertapenem, erythromycin and salts 14. The formulation according to paragraph 2 wherein the thereof, ethambutol HCl and other salts, ethionamide, flo humectant is selected from the group consisting of propylene rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy glycol, glycerin, polyethylene glycol 400 and polyethylene cin, gatifloxacin, gentamycin, imipenem, imipenem-cilastin, glycol 3350. isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, 15. The formulation according to paragraph 2 wherein the lomefloxacin, loracarbef mafenide, marbofloxacin, mero humectant is propylene glycol or purified water. penem, methenamine, methicillin, metronidazole, mezlocil 16. A process for preparing a chewable veterinary formula lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo tion according to paragraph 1 which comprises the steps of: mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, 0207 (a) blending the pharmaceutical agent, hydropho ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy bic material, disintegrant, flavor, cline, paromomycin, penicillin G, penicillin Gaqueous, peni 0208 (b) adding the water, preservative, and the humec cillin G benzatine, penicillin G procaine, penicillin V, peni tant to the mixture from step (a) and mixing the mixture; cillin V penicillin salts and complexes, pentamidine, and piperacillin, piperacillin sodium, piperacillin-taZobactam, 0209 (c) without drying, extruding the mixture. polymixin B. pyrazinamide, rifampin, roXithromycin, salts of 17. A method of achieving bioavailability in an animal of a carbenicillin, silver Sulfadiazine, sparfloxacin, spectinomy therapeutic agent that is comparable to commercially avail cin, spiramycin, Streptomycin, streptozocin, Sufadimethox able products, comprising administering to an animal any one ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, of the formulations of paragraphs 1 through 15. Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam 18. A method for treating a bacterial infection in an animal erazine, Sulfamethazine, Sulfamethixole, Sulfapyridine, Sul comprising administering to the animal any one of the for fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, mulations of paragraphs 1 through 15. taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia 19. The method of paragraph 18 wherein the animal receives mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi treatment on days 0, 7, 14, 21, and 28 comprising adminis cosin, tobramycin, trimethoprim, trimetrexate and ketolides, tering any of the formulations of paragraphs 1 through 15. troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco 20. An antibiotic formulation comprising an antibiotic, a lac mycin and ketolides such as tellithromycin and HMR 3004. tose carrier, a filler, a binder and disintegrant, an aqueous 4. The formulation according to paragraph 2 wherein the Solvent, and optionally a flavor, and optionally color. antibiotic is clindamycin or a pharmaceutically acceptable 21. The formulation according to paragraph 20 wherein the salt or hydrate thereof. antibiotic is between 4 and 15%, the lactose carrier is between 5. The formulation according to paragraph 2 wherein the 40 and 80%, mannitol is between 5 and 15%, the binder and hydrophobic material is selected from the group consisting of disintegrant are between 3 and 10%, the flavor is between 10 glyceryl behenate, hydrogenated vegetable oil, Stearic acid, and 20%, the color is between 0.1 and 0.5%, and the aqueous glyceryl monostearate, glycerylpalmito Stearate or cetyl alco solvent is of a concentration sufficient to q.s. to 100%. hol. 22. The formulation according to paragraph 21 wherein the 6. The formulation according to paragraph 2 wherein the antibiotic is selected from the group consisting of amikacin, hydrophobic material is hydrogenated vegetable oil. aminosalicyclic acid, amoxicillin, amoxicillin and clavulan 7. The formulation according to paragraph 2 where in the ate potassium, amplicillin, azithromycin, bacampicillin, baci filler is selected from the group consisting of soy protein, corn tracin, capreomycin, carbenicillin, carbenicillin indanyl cob, or corn glutton meal. Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, US 2008/01 60067 A1 Jul. 3, 2008

cefazolin, cefazolin Sodium, cefepime, cefinetazole, 30. The formulation according to paragraph 21 wherein the cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, disintegrant is crospovidone. ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin 31. The formulation according to paragraph 21 wherein the Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, flavor is a hickory smoke flavor or a beef flavor. cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, 32. The formulation according to paragraph 21 wherein the ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, colorant is selected from the group consisting of dyes, an cephalothin, cephamandole, cephapirin, cepharadine, ceph aluminum lake, caramel, colorant based upon iron oxide or a prozil, chloramphenicol, chlortetracycline, ciprofloxacin, mixture of any of the foregoing. clarithromycin, clindamycin HCl, clindamycin or salts 33. The formulation according to paragraph 21 wherein the thereof, clindamycin phosphate, clofazimine, cloxacillin, colorant is selected from the group consisting of organic dyes colistin, co-triamoxazole, cycloserine, dalfopristin, danof and titanium dioxide. loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro 34. A process for preparing the chewable veterinary formu streptomycin, dirithromycin, docycycline, efrotomycin, lation according to paragraph 20 which comprises mixing the enoxacin, enrofloxacin, ertapenem, erythromycin and salts ingredients intimately and pressing into single scored tablets. thereof, ethambutol HCl and other salts, ethionamide, flo 35. A method of achieving bioavailability in an animal of a rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy therapeutic agent that is comparable to commercially avail cin, gatifloxacin, gentamycin, imipenem, imipenemi-cilastin, able products, comprising administering to an animal any one isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, of the formulations of paragraphs 20 through 33. lomefloxacin, loracarbef mafenide, marbofloxacin, mero 36. A method for treating a bacterial infection in an animal penem, methenamine, methicillin, metronidazole, mezlocil comprising administering to the animal any one of the for lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo mulations of paragraphs 20 through 33. mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, 37. The method of paragraph 36 wherein the animal receives ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy treatment on days 0, 7, 14, 21, and 28 comprising adminis cline, paromomycin, penicillin G, penicillin Gaqueous, peni tering any of the formulations of paragraphs 20 through 33. cillin G benzatine, penicillin G procaine, penicillin V, peni 38. A long-acting injectable veterinary formulation compris cillin V penicillin salts and complexes, pentamidine, ing an antibiotic, a poloxamer, and sterile water for injection. piperacillin, piperacillin sodium, piperacillin-taZobactam, 39. The formulation according to paragraph 38 wherein the polymixin B. pyrazinamide, rifampin, roXithromycin, salts of antibiotic is between 9 and 18%, the poloxamer is between 5 carbenicillin, silver sulfadiazine, sparfloxacin, spectinomy and 30%, and sterile water for injection is of a concentration cin, spiramycin, Streptomycin, streptozocin, Sufadimethox sufficient to q.s. to 100%. ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, 40. The formulation according to paragraph 39 wherein the Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam antibiotic is selected from the group consisting of amikacin, erazine, Sulfamethazine, Sulfamethixole, Sulfapyridine, Sul aminosalicyclic acid, amoxicillin, amoxicillin and clavulan fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, ate potassium, amplicillin, azithromycin, bacampicillin, baci taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia tracin, capreomycin, carbenicillin, carbenicillin indanyl mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi Sodium, cefaclor, cefadroxil, cefaloridine, cefamandole, cosin, tobramycin, trimethoprim, trimetrexate and ketolides, cefazolin, cefazolin sodium, cefepime, cefinetazole, troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco cefixime, cefinetazole, cefodizime, cefonicid, cefoperaZone, mycin and ketolides such as tellithromycin and HMR 3004. ceforanide, cefotaxime, cefotetan, cefoxitin, cefoxitin 23. The formulation according to paragraph 21 wherein the Sodium, ce?pirome, cefpodoxime, cefpodoxime proxetil, antibiotic is clindamycin or a pharmaceutically acceptable cefauinome, ceftaxidime, ceftibuten, ceftiofur, ceftizoxime, salt or hydrate thereof. ceftriaxone, cefuroxime, cephacelor, cephadrine, cephalexin, 24. The formulation according to paragraph 21 wherein the cephalothin, cephamandole, cephapirin, cepharadine, ceph antibiotic is clindamycin HC1. prozil, chloramphenicol, chlortetracycline, ciprofloxacin, 25. The formulation according to paragraph 21 wherein the clarithromycin, clindamycin HCl, clindamycin or salts filler is selected from the group consisting of anhydrous lac thereof, clindamycin phosphate, clofazimine, cloxacillin, tose, hydrated lactose, sprayed dried lactose, crystalline mal colistin, co-triamoxazole, cycloserine, dalfopristin, danof tose and maltodextrins. loxacin, demeclocycline, dicloxacillin, difloxacin, dihydro 0210 26. The formulation according to paragraph 21 streptomycin, dirithromycin, docycycline, efrotomycin, wherein the filler is lactose. enoxacin, enrofloxacin, ertapenem, erythromycin and salts thereof, ethambutol HCl and other salts, ethionamide, flo 27. The formulation according to paragraph 21 wherein the rfenicol, flumequine, fosfomycin, fosfomycin, gamithromy binder is selected from the group consisting of polyvinyl cin, gatifloxacin, gentamycin, imipenem, imipenemi-cilastin, pyrrolidone, povidone, starch, pregelatinized starch, gelatin, isoniazid, kanamycin, levofloxacin, lincomycin, lineZolid, methylcellulose, hydroxypropyl cellulose, carboxymethyl lomefloxacin, loracarbef mafenide, marbofloxacin, mero cellulose Sodium, ethylcellulose, Sodium alginate, traga penem, methenamine, methicillin, metronidazole, mezlocil canth, and acacia. lin, minocycline, moxifloxacin, nafcillin, nalidixic acid, neo 28. The formulation according to paragraph 21 wherein the mycin, netilmicin, nitrofurantoin, norfloxacin, novobiocin, binder is polyvinyl pyrrolidone. ofloxacin, orbifloxacin, ormetoprim, oxacillin, oxytetracy 29. The formulation according to paragraph 21 wherein the cline, paromomycin, penicillin G, penicillin Gaqueous, peni disintegrant is selected from the group consisting of sodium cillin G benzatine, penicillin G procaine, penicillin V, peni starch glycolate, crospovid one, croScarmellose Sodium, cillin V penicillin salts and complexes, pentamidine, starch, micocrystalline cellulose, alginic acid, Veegum, piperacillin, piperacillin sodium, piperacillin-taZobactam, crospovidone, bentonite, and pregelatinized starch. polymixin B. pyrazinamide, rifampin, roXithromycin, salts of US 2008/01 60067 A1 Jul. 3, 2008 carbenicillin, silver Sulfadiazine, sparfloxacin, spectinomy through 44, wherein the formulation provides Sustained con cin, spiramycin, Streptomycin, streptozocin, Sufadimethox centrations of therapeutic agents for 7-10 days. ine-Ormetoprim, Sulfacetamide, Sulfacytine, Sulfadiazine, 0222. Having thus described in detail preferred embodi Sulfadimethoxine, Sulfadimethoxine-trimethoprim, Sulfam ments of the present invention, it is to be understood that the erazine, Sulfamethazine, Sulfamethixole, Sulfapyridine, Sul invention defined by the above paragraphs is not to be limited fapyrizine, Sulfasalazine, Sulfinethoxazole, Sulfisoxazole, to particular details set forth in the above description as many taZobactam, teicoplanin, tetracycline, tetracycline HCl, tia apparent variations thereof are possible without departing mulin, ticarcillin, ticarcillin and clavulanate potassium, tilmi from the spirit or Scope of the present invention. cosin, tobramycin, trimethoprim, trimetrexate and ketolides, 1. A chewable antibiotic veterinary formulation compris troleanomycin, trovafloxacin, tulathromycin, tylosin, Vanco ing an antibiotic, a hydrophobic material, soy protein fines, a mycin and ketolides such as tellithromycin and HMR 3004. disintegrant, a solvent, and optionally a flavor, and optionally 41. The formulation according to paragraph 39 wherein the a preservative; or antibiotic is clindamycin or a pharmaceutically acceptable comprising an antibiotic between 1 and 5%, a hydrophobic salt or hydrate thereof. material between 2 and 15%, soy protein fines between 42. The formulation according to paragraph 39 wherein the 20-60%, a flavor between 5-30%, a preservative antibiotic is clindamycin phosphate. between 0.2 to 1%, a disintegrant between 2 and 10%, 43. The formulation according to paragraph 39 wherein the and a humectant between 2 and 20% of the formulation. poloxamer is selected from any available poloxamer. 2. The formulation according to claim 1 wherein the anti 44. The formulation according to paragraph 39 wherein the biotic is selected from the group consisting of cefadroxil, poloxamer is poloxamer 407 or poloxamer 188 or a combi cefazolin, cephalexin, cephalothin, cephapirin, cephacelor, nation thereof. cephprozil, cephadrine, cefamandole, cefonicid, ceforanide, 45. A process for preparing the long-acting injectable veteri cefuroxime, cefixime, cefoperaZone, cefotaxime, cefpo nary formulation according to paragraph 38 which comprises doXime, ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, the steps of: cefepime, cefpirome, cefodizime, cefinetazole, cefotetan, 0211 (a) stirring the poloxamer into purified water at 5° cefoxitin, loracarbef, imipenem, erythromycin and salts C.; thereof, azithromycin, clarithromycin, dirithromycin, trolea 0212 (b) optionally adding a second poloxamer to the nomycin, penicillin V penicillin salts and complexes, methi mixture from step (a) and mixing the mixture; and cillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, amoxicil 0213 (c) optionally adding a polyacrylic acid into an lin, amoxicillin and clavulanate potassium, ampicillin, aliquot of water, and completely hydrating the poly bacampicillin, carbenicillin indanyl sodium, salts of carbeni acrylic acid before mixing it into the poloxamer Solution cillin, meZlocillin, piperacillin, taZobactam, ticarcillin, ticar at 5° C.; cillin and clavulanate potassium, clindamycin or salts 0214) (d) neutralizing the Carbopol using triethanola thereof, including clindamycin HCl and clindamycin phos 1C. phate, Vancomycin, novobiocin, aminosalicyclic acid, 0215 (e) dissolving the drug in ethanol/propylene gly capreomycin, cycloserine, ethambutol HCl and other salts, col and adding it to the above Solution. ethionamide, isoniazid, ciprofloxacin, levofloxacin, lom 46. A process for preparing the long-acting injectable veteri efloxacin, enrofloxacin, danofloxacin, marbofloxacin, nalid nary formulation according to paragraph 38 which comprises ixic acid, norfloxacin, ofloxacin, sparfloxacin, Sulfacytine, the steps of: Sulfamerazine, Sulfamethazine, Sulfamethixole, Sulfasala Zine, Sulfisoxazole, Sulfapyrizine, Sulfadiazine, Sulfinethox 0216 (a) dissolving poloxamer 407 completely in water azole, Sulfapyridine, metronidazole, methenamine, fosfomy at room temperature or water pre-cooled to approxi cin, nitrofurantoin, trimethoprim, clofazimine, mately 5° C.: co-triamoxazole, pentamidine, trimetrexate, and ketolides, 0217 (b) dissolving active substances that are insoluble such as tellithromycin and HMR 3004; or in water, in ethanol, isopropanol or propylene glycol, wherein the antibiotic is clindamycin or a pharmaceuti and cally acceptable salt or hydrate thereof. 0218 (c) mixing the therapeutic agent solution with the 3. The formulation according to claim 2 wherein the hydro aqueous phase at 5° C. to form a homogeneous mass. phobic material is selected from the group consisting of glyc 47. A process for preparing the long-acting injectable veteri eryl behenate, hydrogenated vegetable oil, Stearic acid, glyc nary formulation according to paragraph 38 which comprises eryl monostearate, glycerylpalmito Stearate or cetyl alcohol, the steps of: or wherein the hydrophobic material is hydrogenated veg 0219 (a) dissolving poloxamer 407 in water at room etable oil; or temperature at approximately 70° C.; wherein the filler is selected from the group consisting of 0220 (b) dissolving active substances that are insoluble soy protein, corn cob, or corn glutton meal, or in water, in ethanol, isopropanol or propylene glycol at wherein the filler is soy protein; or 70° C.; and wherein the flavor is a hickory smoke flavor orabeef flavor; 0221 (c) mixing the therapeutic agent solution with the O warm aqueous phase to form a homogeneous mass. wherein the preservative is selected from the group con 48. A method for treating a bacterial infection in an animal sisting of parabens (methylparaben and/or propylpara comprising administering to the animal any one of the for ben), benzalkonium chloride, benzethonium chloride, mulations of paragraphs 38 through 44. benzoic acid, benzyl alcohol, bronopol, butylparaben, 49. The method of paragraph 22 wherein the animal receives cetrimide, chlorhexidine, chlorobutanol, chlorocresol, treatment on any of days 0, 7, 14, 21, and 28 comprising cresol, ethylparaben, imidurea, methylparaben, phenol, administering any of the formulations of paragraphs 38 phenoxyethanol, phenylethyl alcohol, phenylmercuric US 2008/01 60067 A1 Jul. 3, 2008 19

acetate, phenylmercuric borate, phenylmercuric nitrate, Zine, Sulfisoxazole, Sulfapyrizine, Sulfadiazine, Sulfinethox potassium Sorbate, sodium benzoate, Sodium propi azole, Sulfapyridine, metronidazole, methenamine, fosfomy onate, Sorbic acid, thimerosal, propyl paraben, myristyl cin, nitro furantoin, trimethoprim, clofazimine, gama-picolinium chloride, paraben methyl, paraben co-triamoxazole, pentamidine, trimetrexate, and ketolides, propyl and quaternary ammonium compounds; or such as tellithromycin and HMR 3004; or wherein the preservative is methylparaben and/or propy wherein the antibiotic is clindamycin or a pharmaceuti lparaben; or cally acceptable salt or hydrate thereof; or wherein the disintegrant is selected from the group consist wherein the antibiotic is clindamycin HC1. ing of Sodium starch glycolate, crospovidone, croscar 8. The formulation according to claim 7 wherein the filler mellose Sodium, starch, micocrystalline cellulose, alg is selected from the group consisting of anhydrous lactose, inic acid, Veegum, crospovidone, bentonite, and hydrated lactose, sprayed dried lactose, crystalline maltose pregelatinized starch; or and maltodextrins; or wherein the disintegrant is crospovidone; or wherein the filler is lactose; or wherein the humectant is selected from the group consist wherein the binder is selected from the group consisting of ing of propylene glycol, glycerin, polyethylene glycol polyvinyl pyrrolidone, povidone, starch, pregelatinized 400 and polyethylene glycol 3350; or starch, gelatin, methylcellulose, hydroxypropyl cellu wherein the humectant is propylene glycol or purified lose, carboxymethyl cellulose Sodium, ethylcellulose, Water. Sodium alginate, tragacanth, and acacia; or 4. A process for preparing a chewable veterinary formula wherein the binder is polyvinyl pyrrolidone; or tion according to any one of claims 1 through 3 which com wherein the disintegrant is selected from the group consist prises the steps of ing of sodium starch glycolate, crospovid one, croscar (a) blending the pharmaceutical agent, hydrophobic mate mellose Sodium, starch, micocrystalline cellulose, alg rial, disintegrant, flavor, inic acid, Veegum, crospovidone, bentonite, and (b) adding the water, preservative, and the humectant to the pregelatinized starch; or mixture from step (a) and mixing the mixture; and wherein the disintegrant is crospovidone; or (c) without drying, extruding the mixture. wherein the flavor is a hickory smoke flavor orabeef flavor; 5. A method of achieving bioavailability in an animal of a O therapeutic agent that is comparable to commercially avail wherein the colorant is selected from the group consisting able products, comprising administering to an animal any one of dyes, an aluminum lake, caramel, colorant based upon of the formulations of claims 1 through 3 wherein the animal iron oxide or a mixture of any of the foregoing; or receives treatment on days 0, 7, 14, 21, and 28, wherein wherein the colorant is selected from the group consisting administration is useful for treating a bacterial infection in an of organic dyes and titanium dioxide. animal. 9. A process for preparing the formulation according to 6. A tablet Veterinary formulation comprising an antibiotic, claim 8 which comprises mixing the ingredients intimately a lactose carrier, a filler, a binder and disintegrant, an aqueous and pressing into single scored tablets. Solvent, and optionally a flavor, and optionally color; or 10. A method of achieving bioavailability in an animal of a comprising an antibiotic between 4 and 15%, a lactose therapeutic agent that is comparable to commercially avail carrier between 40 and 80%, mannitol between 5 and able products, comprising administering to an animal any one 15%, a binder and disintegrant between 3 and 10%, a of the formulations of claims 6 through 8; or flavor between 10 and 20%, color between 0.1 and 0.5%, comprising administering to the animal any one of the and an aqueous solvent of a concentration Sufficient to formulations of claims 6 through 8; wherein the animal q.S. to 100%. receives treatment on days 0, 7, 14, 21, and 28 wherein 7. The formulation according to claim 6 wherein the anti Such administration is useful for treating a bacterial biotic is selected from the group consisting of cefadroxil, infection. cefazolin, cephalexin, cephalothin, cephapirin, cephacelor, 11. A long-acting injectable formulation comprising: cephprozil, cephadrine, cefamandole, cefonicid, ceforanide, an antibiotic between 1 and 50%, a poloxamer between 1 cefuroxime, cefixime, cefoperaZone, cefotaxime, cefpo and 50%, and sterile water for injection of a concentra doXime, ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, tion sufficient to q.s. to 100%; or cefepime, cefpirome, cefodizime, cefinetazole, cefotetan, an antibiotic between 8 and 20%, a poloxamer between 1 cefoxitin, loracarbef, imipenem, erythromycin and salts and 50%, and sterile water for injection of a concentra thereof, azithromycin, clarithromycin, dirithromycin, trolea tion sufficient to q.s. to 100%; or nomycin, penicillin V penicillin salts and complexes, methi an antibiotic between 9 and 18%, a poloxamer between 1 cillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, amoxicil and 50%, and sterile water for injection of a concentra lin, amoxicillin and clavulanate potassium, amplicillin, tion sufficient to q.s. to 100%; or bacampicillin, carbenicillin indanyl sodium, salts of carbeni an antibiotic between 9 and 18%, a poloxamer between 5 cillin, meZlocillin, piperacillin, taZobactam, ticarcillin, ticar and 40%, and sterile water for injection of a concentra cillin and clavulanate potassium, clindamycin or salts tion sufficient to q.s. to 100%; or thereof, including clindamycin HCl and clindamycin phos an antibiotic between 9 and 18%, a poloxamer between 10 phate, Vancomycin, novobiocin, aminosalicyclic acid, and 30%, and sterile water for injection of a concentra capreomycin, cycloserine, ethambutol HCl and other salts, tion sufficient to q.s. to 100%. ethionamide, isoniazid, ciprofloxacin, levofloxacin, lom 12. The formulation according to claim 11 wherein the efloxacin, enrofloxacin, danofloxacin, marbofloxacin, nalid antibiotic is selected from the group consisting of cefadroxil, ixic acid, norfloxacin, ofloxacin, sparfloxacin, Sulfacytine, cefazolin, cephalexin, cephalothin, cephapirin, cephacelor, Sulfamerazine, Sulfamethazine, Sulfamethixole, Sulfasala cephprozil, cephadrine, cefamandole, cefonicid, ceforanide, US 2008/01 60067 A1 Jul. 3, 2008 20 cefuroxime, cefixime, cefoperaZone, cefotaxime, cefpo (b) optionally adding a second poloxamer to the mixture doXime, ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, from step (a) and mixing the mixture; and cefepime, cefpirome, cefodizime, cefinetazole, cefotetan, (c) optionally adding a polyacrylic acid into an aliquot of cefoxitin, loracarbef, imipenem, erythromycin and salts water, and completely hydrating the polyacrylic acid thereof, azithromycin, clarithromycin, dirithromycin, trolea before mixing it into the poloxamer solution at 5° C.; nomycin, penicillin V penicillin salts and complexes, methi (d) neutralizing the Carbopol using triethanolamine. cillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, amoxicil (e) dissolving the drug in ethanol/propylene glycol and adding it to the above solution; lin, amoxicillin and clavulanate potassium, amplicillin, or, which comprises the steps of bacampicillin, carbenicillin indanyl sodium, salts of carbeni (a) dissolving poloxamer 407 completely in water at room cillin, meZlocillin, piperacillin, taZobactam, ticarcillin, ticar temperature or water pre-cooled to approximately 5° C. cillin and clavulanate potassium, clindamycin or salts (b) dissolving active substances that are insoluble in water, thereof, including clindamycin HCl and clindamycin phos in ethanol, isopropanol or propylene glycol phate, Vancomycin, novobiocin, aminosalicyclic acid, (c) mixing the therapeutic agent solution with the aqueous capreomycin, cycloserine, ethambutol HCl and other salts, phase at 5° C. to form a homogeneous mass; ethionamide, isoniazid, ciprofloxacin, levofloxacin, lom or, which comprises the steps of efloxacin, enrofloxacin, danofloxacin, marbofloxacin, nalid (a) dissolving poloxamer 407 in water at room temperature ixic acid, norfloxacin, ofloxacin, sparfloxacin, Sulfacytine, at approximately 70° C. Sulfamerazine, Sulfamethazine, Sulfamethixole, Sulfasala (b) dissolving active substances that are insoluble in water, Zine, Sulfisoxazole, Sulfapyrizine, Sulfadiazine, Sulfinethox in ethanol, isopropanol or propylene glycol at 70° C. azole, Sulfapyridine, metronidazole, methenamine, fosfomy (c) mixing the therapeutic agent solution with the warm cin, nitro furantoin, trimethoprim, clofazimine, aqueous phase to form a homogeneous mass. co-triamoxazole, pentamidine, trimetrexate, and ketolides, 15. A method for treating a bacterial infection in an animal such as tellithromycin and HMR 3004; or comprising administering to the animal any one of the for wherein the antibiotic is clindamycin or a pharmaceuti mulations of claims 11 through 13 or claim 17. cally acceptable salt or hydrate thereof; or 16. The method of claim 15 wherein the animal receives wherein the antibiotic is clindamycin phosphate. treatment on any of days 0, 7, 14, 21, and 28 comprising administering any of the formulations of claims 38 through 13. The formulation according to claim 11 wherein the 44, wherein the formulation provides Sustained concentra poloxamer is selected from any available poloxamer, or tions of therapeutic agents for 7-10 days. wherein the poloxamer is poloxamer 407 or poloxamer 188 17. The formulation according to claim 11 wherein the or a combination thereof. antibiotic is clindamycin phosphate at 9-18%, and the polox 14. A process for preparing the long-acting injectable vet amer is poloxamer 407 or poloxamer 188 or a combination erinary formulation according to any one of claims 11, 12, 13 thereof at 5-30%. or 17 which comprises the steps of: (a) stirring the poloxamer into purified water at 5°C.;