Formulations of florfenicol and methods for solubilizing florfenicol

Abstract

Formulations and methods for obtaining a solution that includes Florfenicol and water, wherein the Florfenicol is dissolved in the water and is stable for at least 8 hours after mixing into solution.

Description

FORMULATIONS OF FLORFENICOL AND METHODS FOR SOLUBILIZING FLORFENICOLCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to US provisional patent application number US 63 / 682,658, filed on August 13, 2024, which is herein incorporated by reference in its entirety.FIELD

[0002] The present disclosure relates generally to formulating a compound to be in a soluble form for treatment of animals.BACKGROUND

[0003] Florfenicol is a carboxamide that is the N-dichloroacetyl derivative of (lR,2S)-2-amino-3- fluoro-l-[4-(methanesulfonyl)phenyl]propan-l-ol. Florfenicol has the following structure:Florfenicol is a synthetic antibiotic, which can inhibit bacterial protein synthesis by impairing peptidyl transferase activity. Protein synthesis can be inhibited in both prokaryotic and eukaryotic (mitochondrial) ribosomes. It is generally understood and accepted that Florfenicol has a significant water insoluble property (i.e., with an estimated water solubility of 0.9 mg / ml or less in water). Generally, it is understood that Florfenicol is soluble only in aprotic solvents, and thus Florfenicol precipitate out rapidly and cause breakdown of the product when exposed to water based systems.SUMMARY

[0004] Any or all portion(s) of any of the embodiments disclosed herein may be combined with any other portion(s) of any embodiment.

[0005] In some embodiments, the animal being treated is a farm animal. In some embodiments, the animal is at least one of a pig, poultry, a cattle, a sheep, a horse, a dog, and / or a cat.

[0006] The embodiments of formulations and methods disclosed herein are directed towards a solution that includes Florfenicol and water, wherein the Florfenicol is dissolved in the water and is stable for at least 8-12 hours after mixing into solution. According to some embodiments, the solution is stable for at least 12 hours after mixing into solution with water. According to some embodiments, the solution is stable for at least 24 hours after mixing into solution with water. According to some embodiments, the solution is stable for at least 36 hours after mixing into solution with water. According to some embodiments, the solution is stable for at least 48 hours after mixing into solution with water. According to some embodiments, the solution is stable for at least 72 hours after mixing into solution with water. According to some embodiments, the solution is stable for at least 3 days after mixing into solution with water. According to some embodiments, the solution is stable for at least 4 days after mixing into solution with water. According to some embodiments, the solution is stable for at least 5 days after mixing into solution with water. According to some embodiments, the solution is stable for at least 6 days after mixing into solution with water. According to some embodiments, the solution is stable for at least 7 days after mixing into solution with water. According to some embodiments, the solution is stable for at least 8 days after mixing into solution with water. According to some embodiments, the solution is stable for at least 9 days after mixing into solution with water. According to some embodiments, the formulation includes 0.01 gm to 5 gm of cellulose and / or cellulose derivative per gram of Florfenicol. According to some embodiments, the formulation includes povidone of 5 % (wt / vol) to 40 % (wt / vol). According to some embodiments,the formulation includes Florfenicol and an NSAID (e.g., meloxicam) for treatment of infection and inflammation.DETAILED DESCRIPTION

[0007] Disclosed herein are formulations of Florfenicol and methods for solubilizing Florfenicol in water, wherein embodiments of concentrated formulations maintain antibiotic potency and stability in a water-based system. Many of the embodiments of the formulations can be diluted in a stock tank environment to achieve a target dose that would be utilized in a treatment scenario. Generally, a particular dosage concentration can be achieved is 13.47 mg / ml in the stock tank environment that would be diluted out at a 1:128 ratio.

[0008] Generally, one can prepare and administer Florfenicol is by taking an insoluble powdered form of the product and diluting it in Propylene Glycol (an exemplary aprotic solvent). This solution can be administered undiluted into a water medication system for administration into a whole herd of animals. At the 1:128 ratio (i.e., 1 ounce per gallon of water), the Florfenicol can remain in solution, but the product begins precipitating out immediately if water is added in any form into the stock tank environment. This lack of stability can be a major problem.

[0009] The following Comparative Examples of some formulations of Florfenicol (in aprotic solvent and in solid form) show its general properties of insolubility and instability in water:Comparative Example 1. Florfenicol with Propylene Glycol a. Florfenicol Injectable 300 mg / ml : 170 ml b. Propylene Glycol: Q.S. to 3785 ml c. Administered undiluted in stock solution

[0010] Comparative Example 1 was not stable in water, which is a major issue. This formulation showed an inability to add any dilution or water to it. Therefore, Comparative Example 1 was limited to the concentration that can be made in a stock tank. Further, when wateris added to this formulation, Florfenicol quickly precipitates and becomes unusable in the stock tank environment.Comparative Example 2. Florfenicol Liquid Concentrate for dilution a. Florfenicol powder b. Binding agent of 0.5 to 5.0 % c. 40-80 % by weight of a filler

[0011] Comparative Example 2, which is a powder compound, can be diluted to a concentration of 1.347 % (wt / vol) by adding a very specific amount of water to the container immediately prior to administering out into the stock tank environment. However, the solid (powder) product cannot be used with water that has greater than a hardness level of 250 ppm. Accordingly, a purified (e.g., distilled) water must be used to avoid crystallization of the product (which is a major problem). Also, as water is added at a larger ratio of the dilution environment, Florfenicol quickly precipitates and becomes unusable in the stock tank environment.

[0012] Similar to the above Comparative Examples, over several dozens of formulations showed the generally accepted understanding that Florfenicol is insoluble and instable in presence of water.

[0013] In contrast to the above Comparative Examples, the embodiments of the formulations described herein (shown as Examples below) are directed towards achieving solubility and stability of Florfenicol by taking advantage of the protective nature of glycols which can provide with ether linkages to a molecule. Micelle and ether-based products can play an important role for providing a stable concentrate that is stable in anhydrous and water-based systems.

[0014] EXAMPLES OF FORMULATIONS

[0015] Surprisingly and unexpectedly, the following formulations achieved successful results of solubility and stability (stable solubility: being soluble over an extended amount of time) in water. It is noted these are not necessarily limiting examples but provide exemplary embodiments for demonstration of the breakthrough achieved. All Examples have been able to be diluted in nearly any type of water sample provided. All of the Examplesmaintain proper potency and minimal to no precipitation in the diluted environment for a minimum of 24 hours. As used herein, the term "methylcellulose" includes any type of cellulose and / or cellulose derivative(s). Examples of methylcellulose, as used herein, can include one or more of hydroxypropyl cellulose, carboxymethylcellulose, alpha cellulose, cellulose acetate, hydroxyethyl cellulose, methylcellulose, low viscosity methylcellulose, hydroxypropylmethylcellullose, or any combinations thereof. Examples of commercially available methylcellulose are Methocel™, E3 Methocel™, and E3LV Methylcellulose. As used herein, the term "povidone" includes any one or more of VP, Polyvidone, Povidone, Polyvinylpyrrolidone, or any combinations thereof. According to some embodiments, the water used is not distilled water. According to some embodiments, the water used is not purified water. According to some embodiments, the water used is sourced from wells and / or others where the water contains impurities (e.g., hard water).

[0016] Example # 1Florfenicol 3.51 % (wt / vol)Florfenicol 3.51 gmPovidone K-25 10 gmMethylcellulose 0.5 gmPEG 400 Q.S. to 100 mlNote: This Example stayed without precipitation when diluted at a 2.5 pi nt / ga lion of stock solution showing. This showed the potential when combining a methylcellulose derivative with a povidone. The product was easy to make in the concentrate environment and then easily diluted in stock tank environment.

[0017] Example It 2Florfenicol 4.25 % (wt / vol)Florfenicol 4.25 gmPovidone 10 gmMethylcellulose 1.0 gmPEG 400 (polyethylene glycol 400) Q.S. to 100 mlNote: This was an improvement upon Example #1 above. The concentration of Florfenicol was increased along with increasing slightly the amount of E3. This sample was stable for >72 hours in stock solution when water was added to it.

[0018] Example it 3Florfenicol 3.51 % (wt / vol)Florfenicol 3.51 gmMethylcellulose 4.0 gmTranscutol 30 mlPEG 400 Q.S. to 100 mlNote: Example #3 was diluted at a rate of 3 pints / ga Hon of stock solution again showing a significant improvement over the current non dilutable formulations discussed above.It also showed the ability of being able to use a Transcutol which is a novel ether based glycol that can be used in combination with a methylcellulose. This Example #3 remained unchanged (i.e ., stable) in the diluted water based solution for greater than 9 days.

[0019] Example # 4Florfenicol 3.51 % (Wt / Vol)Florfenicol 3.51 gmTranscutol 30 mlPovidone K-2510 gmPEG 400 Q.S. to 100 mlNote: Example #4 was a 3 pint / ga I Ion dilution experiment that showed the ability to make a stable dilutable Florfenicol product in water without the usage of methylcellulose. It should be noted however, that it was discovered after Experiment 3 and 4 that Transcutol could not be used with higher concentrated products as failures would be seen occurring.

[0020] Example #5Florfenicol 1.17 % (wt / vol)Florfenicol 1.17 gmPolysorbate 80 5 mlPotassium Sorbate 13 gmPoloxamer 407 8 gmPropylene Glycol Q.S. 100 mlNote: This sample was the only success achieved with using polysorbate, and excluding Povidones or Methylcellulose from the formulation.

[0021] Example #6Florfenicol 4.25 % (wt / vol)Florfenicol 4.25 gmHydroxypropylmethylcellulose 0.8 gmPovidone K-30 12.8 gmPropylene Glycol Q.S. to 100 mlNote: The Povidone K-30 can be substituted out for Povidone K-25 or other Povidone polymers. It should also be noted that increasing the percentage up to 25 % in experimentation only improved the ability to withstand precipitation in the diluted stock solution environment. In this case 2.5 pints worth of concentrated material was diluted into a gallon of water based stock solution.

[0022] Example #7Florfenicol 4.25 % (Wt / vol)Florfenicol 4.25 gmHydroxypropylmethylcellulose 0.8 gmPovidone K-30 12.8 gmPEG 400 Q.S. to 100 mlNote: The Povidone K-30 can be substituted out for Povidone K-25 or other Povidone polymers. It should also be noted that increasing the percentage up to 25 % in experimentation only improved the ability to withstand precipitation in the diluted stock solution environment. In this case 2.5 pints worth of concentrated material was diluted into a gallon of water based stock solution.

[0023] As part of this process the Examples were stress tested in well water environments to ensure improvement in a real world scenario. The following is water results from one of the well water sites and also the control purified USP water used in the lab. It shows the wide variance and significant amount of dissolved solids and material that could serve as precipitation points for unstable products. The fact that the current formulations handle this environment and show no significant degradation is unexpected and surprising.

[0024] Flo rfenicol precipitates and crystalizes out as it is further diluted by water (e.g., more water present along with water hardness, the harder it is to keep the Florfenicol in stable stock solution). The following additional Examples further surprising and unexpected results.

[0025] Example #8Florfenicol 26.56 gmTween 80 150 mlGlycerol Formol 100 mlHydroxypropyl methyl cellulose 4 gmTranscutol 25 mlQ.S. to 500 mlExample #8 was stable to 8-12 hours prior to precipitation when diluted to a ratio of 2 pints / gallon of stock solution

[0026] Example #9Florfenicol 160.86 gmPEG400 2800 mlHydroxypropyl methyl cellulose 30.28 gmPovidone K-30 296.5 gmPovidone K-25 157.71 gmExample #9 was found to be stable when it was agitated for 24 hours. It was also stable when not agitated. The formulation was diluted at a rate of 2.5 pints / gallon. The agitated sample had no crystallization for 96 hours after being exposed to heat of 150 degrees Fahrenheit for 24 hours. This was thought to show heat and agitation were important for stabilization. It should also be noted the non-agitated and heated sample showed minor crystallization at 24 hours, but maintained >90 % potency when tested.

[0027] Example #10Florfenicol 12.74 gmHydroxypropyl methyl cellulose 2.4 gmPovidone K-25 12.5 gmPovidone K-30 23.5 gmPEG 400 221.92 mlExample #10 was diluted at a 2.5 pint of concentrate in 1 gallon of stock solution.Example #10 showed solubility, stability, and potency in both farm water and purified water with HPLC testing. Samples had no crystallization at 24 hours. Below is the sample site water tested that product performed in. At after 7 days, the stock solution sample has not precipitated out or shown breakdown. Surprisingly this was found to be a very stable dilution.Mineral Panel in Fluids by ICP-MS Specimen = Water Species = PorcineElement Unit Range 1 , SID #1 2, SID #2Calcium ppm - 231.8 157.3Copper ppm — < 0.1 < 0.1Iron ppm — 0.2 1.1Magnesium ppm 65.4 45.9Manganese ppb — 732 161Molybdenum ppb - 5 5Phosphorus ppm — < 2.0 < 2.0Potassium ppm — 5.9 5.2Selenium ppb - < 2 < 2Zinc ppm - 0.1 < 0.1

[0028] Example #11Florfenicol 42.39 gmMeloxicam 32 tabletsArginine 5 gmNiacinamide 2.4 gmPovidone K-25 42.4 gmHydroxypropyl methyl cellulose 8 gmPovidone K-30 78.33 gmPEG 400 666.67 mlExample #11 was used to test the ability to dilute at a 2.5 pint / gallon rate withMeloxicam added to provide a combination product that could incorporate both anantibiotic and anti-inflammatory drug such as Meloxicam. The product surprisingly showed no signs of precipitation at 24 hours.

[0029] Example #12Florfenicol 53.13 gmHydroxypropyl methyl cellulose 10 gmPovidone K-25 66 gmPovidone K-30 132 gmPEG 400 377.9 gm first, then then reaming 300 gm afterProduct agitated with heat of 70 degrees Celsius for 90 minutesExample #12 was prepared at a 2 pint / ga lion dilution. This formulation was agitated and heated. The product passed with no noticeable precipitation at 24 hours in both purified water and well water samples. The sample also passed an initial test at 24 hours withHPLC testing showing 100% potency.Mineral Panel in Fluids by ICP-MSSpecimen = WaterSpecies = PorcineElement Unit Range 1 , SID #1 2, SID #2Calcium ppm — 231.8 157.3Copper ppm < 0.1 < 0.1Iron ppm - 0.2 1.1Magnesium ppm — 65.4 45.9Manganese ppb - 732 161Molybdenum ppb — 5 5Phosphorus ppm - < 2.0 < 2.0Potassium ppm - 5.9 5.2Selenium ppb — < 2 < 2Zinc ppm - 0.1 < 0.1

[0030] Example #13Florfenicol 42.39 gmHydroxypropyl methyl cellulose 10 gmPovidone K-30 120 gmPEG 400 834.39 gmExample #13, diluted to 2.5 pi nt / ga I Ion dilution, passed with flying colors showing that even without K-25, K30 will work as the sole povidone.

[0031] Example #14Florfenicol 53.13 gmHydroxypropyl methyl cellulose 10 gmPovidone K-30 132 gmPovidone K-25 66.00 gmPEG 677.90 gmHeated with agitation for 2 hours at 90 degrees Celsius.Example #14 was a 2 pi nt / ga I Io n dilution. Example #14 showed >95% via HPLC potency, and showed stability of formulation for 24 hours.

[0032] Example #15Florfenicol 53.13 gmHydroxypropyl methyl cellulose 10 gmPovidone K-30 220.01 gmPEG 400 585.86 gmHeated with agitation for 2 hours at 90 degrees Celsius.Example #15 was a 2 pi nt / gallon dilution. Example #15 showed >95% via HPLC potency and showed stability of formulation for 24 hours. It also demonstrated that K-30 alone could be used in place of a K-25 & K30 combination.

[0033] Example #16Florfenicol 53.13 gmHydroxypropyl methyl cellulose 10 gmPovidone K-30 220.01 gmTween 80 330.20 gmPEG 400 297.2 gmHeated with agitation for 2 hours at 90 degrees Celsius.Example #16 also passed at 24 hours with no signs of precipitation and passed potency testing. It was determined that Example #16 showed that Tween 80 can be used with or in place of PEG 400 as a base solvent.

[0034] Example #17Florfenicol 160.8 gmMeloxicam 1.830 gmNiacinamide 9.15 gmHydroxypropyl methyl cellulose 32.0 gmPVP K-30 530 gmPEG 400 Q.S. to 3785 mlExample #17 included Meloxicam in a concentrated Florfenicol solution relying on hydrotropic properties in an organic solvent. The product was agitated and mixed until a uniform solution was produced. Example #17 was diluted in 3 different stock solution environments at a rate of 2.5 pints / 1 gallon of water (e.g., to achieve a commercial dosage in stock tank environments for treatment of animals, such as swine). Example #17 was found to be surprisingly stable in all stock solution environments with no precipitation occurring even at (or up to) 96 hours post mixing. All samples tested out >90% via HPLC at the 24 hour time point as well without the need for agitation of the solution. This showed the ability to prepare a stable concentrated product that could also be used to deliver a combination product containing an NSAID (potential examples including but not all encompassing: Ibuprofen, Meloxicam, Piroxicam, Aspirin, Indomethacin, Ketoprofen, etc.).

[0035] Example #18Florfenicol 160.8 gmHydroxypropyl methyl cellulose 32.0 gmPVP K-30 530 gmPEG 400 Q.S. to 3785 mlExample #18 was found to be successful when it was agitated for 24 hours. Example #18 was diluted at a rate of 2.5 pints / gallon. Example #18 showed no sign of precipitation orcrystallization at 96 hours post mixing in any of the 3 water quality samples utilized.Below are the sample site waters tested that product performed in. Purified USP water was utilized as the control stock solution environment.Mineral Panel in Fluids by ICP-MS Specimen = Water Species = PorcineElement Unit Range 1 , SID #1 2, SID #2Calcium PPm 231.8 157.3Copper PPm < 0.1 < 0.1Iron PPm 0 2 1 1Magnesium PPm 65.4 45.9Manganese PPb 732 161 Molybdenum PPb 5 5 Phosphorus PPm < 2.0 < 2.0Potassium PPm 5.9 5 2Selenium PPb < 2 < 2Zinc PPm 0.1 < 0.1Mineral Panel in Fluids by ICP-MSSpecimen = WaterSpecies = PorcineElement Unit Range 1 , SID #1 2, SID #2Calcium ppm - 231.8 157.3Copper ppm - < 0.1 < 0.1Iron ppm - — 0.2 1.1Magnesium ppm - 65.4 45.9Manganese ppb — - 732 161Molybdenum ppb - 5 5Phosphorus ppm - < 2 0 < 2 0Potassium ppm - 5.9 5.2Selenium ppb - < 2 < 2Zinc ppm — 0.1 < 0.1

[0036] Additional Experiments were carried out looking at adjusting different components of the embodiments to provide a concentrate that could better withstand challenges of farm water or non-purified water used in the formulations. The following will share the formulations and results at various timepoints.

[0037] All of the Examples 19 - 28 were carried out using significantly challenged water samples. Challenged water means that the water and / or conditions of the water are not purified water and / or distilled water. Accordingly, challenged water can be hard water and / or at a temperature that is not generally ideal for solubilizing formulations. These challenged water samples and Florfenicol were kept at least refrigerated before the stock solution was made to ensure the most challenged systems. This is due to the fact that as temperature decreases the preferred carrier of PEG 400 may gel or thicken which can impair mixing and therefore leave Florfenicol exposed to risk of greater precipitation. It was confirmed in multiple field tests that the colder water that had more sedimentation or hardness would increase potential risk of precipitation. Therefore, these tests show the surprising and unexpected properties which can be further manipulated to handle challenged environments to deliver a stable product to the animal(s). In these examples, all stock solutions were configured to be mixed for delivery of full dose prescribed in Florfenicol treatments. In this case the ratio is roughly 2.5 pints per 1 gallon of stock solution. Further, in these examples, injectable Florfenicol were utilized as starting material to be compliant from a compounding standpoint with some animals.

[0038] Example #19Florfenicol 4.25gm from 300mg / ml Injectable (4.25%)Povidone K-30 12.8 gmHydroxypropyl MethylCellulose (Hypromellose) 0.8 gm PEG400 50%PEG300 50% Q.S. lOO mLResults: Precipitation was seen, but overall there was an improvement compared to a previous attempt utilizing only PEG300. One of the theories on why a PEG mixture was used was to increase the stability and lower the freezing point when compared to just PEG 400 by itself.

[0039] Example #20Florfenicol 4.25gm from 300mg / ml Injectable (4.25%)Povidone K-30 12.8 gmHydroxypropyl MethylCellulose (Hypromellose) 0.8 gmPEG400 25%PEG300 75% Q.S. 100 mLResults: Sample had no precipitation in challenged water for at least 17 hours from mixing. Surprisingly this was found to be the case after 3 consecutive freeze and thaw cycles showing the stabilizers were not affected when exposed to harsh conditions. This continued trends seen with freeze thaw samples conducted on other formulations.

[0040] Example #21Florfenicol 4.04gm from 300mg / ml injectable (4.04%)Povidone K-30 12.8 gmHydroxypropyl MethylCellulose (Hypromellose) 0.8 gmPEG400 50%PEG300 50% Q.S. 100 mL 74 mL total PEG mixture to Q.S. 100 mLResults: No precipitation seen at 24 hours, and minimal (less than 5-10 particulates) at 48 hours. Sample also maintained less than 50 particulates of precipitation at 72 hours. This sample was also exposed to 2 freeze / thaw cycles with similar results seen at 24 hours.

[0041] Example #22Florfenicol 4.25gm from 300mg / ml Injectable (4.25%)Povidone K-30 14 gmHydroxypropyl MethylCellulose (Hypromellose) 0.8 gmPEG400 25%PEG300 Q.S. 100 mL 74 mL total PEG mixture to Q.S. 100 mLResults: Sample was subjected to 2 freeze / thaw cycles but surprisingly held up well with minimal precipitation at 24 hours.

[0042] Example #23Florfenicol 4.04gm from 300mg / ml Injectable (4.04%)Povidone K-30 19.2 gmHydroxypropyl MethylCellulose (Hypromellose) 0.8 gmPEG400 25%PEG300 75% - Q.S. 100 mL 70 mL total PEG mixture to Q.S. 100 mLResults: This sample showed almost no precipitation at 72 hours post stock solution mixture. It also withstood 3 freeze / thaw cycles prior to stock solution mixture without breaking down.

[0043] Example #24Florfenicol 4.04gm from 300mg / ml Injectable (4.04%)Povidone K-30 21 gmHydroxypropyl MethylCellulose (Hypromellose) 0.82 gmPEG400 25%PEG300 75% - Q.S. 100 mL Q.S. volume 125 mLPEG mixture Formulated as 200 mL sample (quantities x2)Results: No precipitation seen at 24 hours even with water sample that had > 1660ppm total dissolved solids

[0044] Example #25Florfenicol 3.368gm from 300mg / ml Injectable (3.368%)Povidone K-30 14 gmHydroxypropyl MethylCellulose (Hypromellose) 0.82 gmPEG400 25%PEG300 75% - Q.S. 100 mL Q.S. volume 152 mLPEG mixture Formulated as 200 mL sample (quantities x2)Results: No evidence of precipitation was seen in either test sample at 72 hours post mixing into stock solution

[0045] Example #26Florfenicol 3.51 gm from 300mg / ml injectable (3.51%)Povidone K-25 10 gmHydroxypropyl MethylCellulose (Hypromellose) 0.82 gmPEG400 25%PEG300 75% - Q.s. 100 mL Formulated as 200 mL sample (quantities x2)Total Q.S. volume for 200 mL sample 145 mL of PEG mixture.Results: No precipitation seen at 72 hours

[0046] Example #27Florfenicol 4.25gm from 300mg / ml injectablePovidone K-30 13.60gmPovidone K-25 7.40gmHydroxypropyl MethylCellulose (Hypromellose) 0.82gmPeg400 25%Peg 300 75%Formulated as 2 200ml samplesResults: No precipitation at 24 hours

[0047] The following is the summary of the well water used in these tests. As can be seen both samples were significantly above the limits of historical products containing Florfenicol for water administration thus showing the continued power of this invention.

[0048] According to some embodiments, the surprising and unexpected properties described herein can be further enhanced by adding a chelator agent to the formulation(s) to further improve stability in the stock solution environment. It was observed that with reduced visible debris burden in stock solution that Florfenicol stock solutions behaved better over time. Thus, a chelator that could bind certain Calcium or other metal ions in the hard water systems might further enhance the products stability. According to some embodiments, a chelator agent is and / or includes EDTA.

[0049] Example #28Florfenicol 4.25gmPovidone K-30 12.8gmHydroxypropyl MethylCellulose (Hypromellose) 0.8gm EDTA 0.5gmPeg 400 Q.S. to 100ml

[0050] This exemplary formulation was mixed in extremely challenged water system as described above, and found to have no precipitation at 24 hours compared to some signs of precipitation in a control sample. This formulation experiment was repeated against a control sample without EDTA and put into two different water settings. The first was a repeat of the challenged water system, and the second had 10% by weight of mud and debris added to stress the system further. It was found that by 40 hours the EDTA sample had no precipitation visible while the other sample began struggling around the 20 hour mark.

[0051] Among those benefits and improvements that have been disclosed, other objects and advantages of this disclosure will become apparent from the following description taken in conjunction with the accompanying figures. Detailed embodiments of the present disclosure are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the disclosure that may be embodied in various forms. In addition, each of the examples given regarding the various embodiments of the disclosure which are intended to be illustrative, and not restrictive.

[0052] Clauses:

[0053] Clause 1. A composition comprising: a clear single phase solution, including: water; and Florfenicol, wherein the Florfenicol is dissolved in the water and has stable solubility for at least 8-12 hours after mixing into solution.

[0054] Clause 2. The composition of clause 1, wherein the stable solubility is for at least 24 hours after mixing into solution.

[0055] Clause 3. The composition of clause 1, wherein the stable solubility is for at least 36 hours after mixing into solution.

[0056] Clause 4. The composition of clause 1, wherein the stable solubility is for at least 48 hours after mixing into solution.

[0057] Clause 5. The composition of clause 1, wherein the stable solubility is for at least 3 days after mixing into solution.

[0058] Clause 6. The composition of clause 1, wherein the stable solubility is for at least 4 days after mixing into solution.

[0059] Clause 7. The composition of clause 1, wherein the stable solubility is for at least 5 days after mixing into solution.

[0060] Clause 8. The composition of clause 1, wherein the stable solubility is for at least 6 days after mixing into solution.

[0061] Clause 9. The composition of clause 1, wherein the stable solubility is for at least 7 days after mixing into solution.

[0062] Clause 10. The composition of clause 1, wherein the stable solubility is for at least 8 days after mixing into solution.

[0063] Clause 11. The composition of clause 1, wherein the stable solubility is for at least 9 days after mixing into solution.

[0064] Clause 12. The composition of any of clauses 1-11, wherein the stable solubility is up to 9 days after mixing into solution.

[0065] Clause 13. The composition of any of clauses 1-12, further comprising 0.01 gm to 5 gm of cellulose and / or cellulose derivative per gram of Florfenicol.

[0066] Clause 14. The composition of any of clauses 1-13, further comprising povidone of 5 % (wt / vol) to 40 % (wt / vol).

[0067] Clause 15. The composition of any of clauses 1-14, further comprising an NSAID

[0068] Clause 16. The composition of clause 15, wherein the NSAID includes meloxicam.

[0069] Clause 17. The composition of any of clauses 1-16, further comprising a chelator agent.

[0070] Clause 18. The composition of clause 17, wherein the chelator agent includes EDTA.

[0071] Clause 19. A method of treatment for infection and inflammation, comprising: obtaining the composition according to any of clauses 1-18; and providing the composition to an animal for drinking.

[0072] The terminology used herein is intended to describe embodiments and is not intended to be limiting. The terms "a," "an," and "the" include the plural forms as well, unless clearly indicated otherwise. The terms "comprises" and / or "comprising," when used in this Specification, specify the presence of the stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, and / or components. As used herein, the term "based on" is not exclusive and allows for being based on additional factors not described, unless the context clearly dictates otherwise. In addition, the meaning of "in" includes "in" and "on."

[0073] It is to be understood that changes may be made in detail, especially in matters of the construction materials employed and the shape, size, and arrangement of parts without departing from the scope of the present disclosure. This Specification and the embodiments described are examples, with the true scope and spirit of the disclosure being indicated by the claims that follow.

Claims

CLAIMSWhat is claimed is:

1. A composition comprising: a clear single phase solution, including: water; andFlorfenicol, wherein the Florfenicol is dissolved in the water and has stable solubility for at least 8-12 hours after mixing into solution.

2. The composition of claim 1, wherein the stable solubility is for at least 24 hours after mixing into solution.

3. The composition of claim 1, wherein the stable solubility is for at least 36 hours after mixing into solution.

4. The composition of claim 1, wherein the stable solubility is for at least 48 hours after mixing into solution.

5. The composition of claim 1, wherein the stable solubility is for at least 3 days after mixing into solution.

6. The composition of claim 1, wherein the stable solubility is for at least 4 days after mixing into solution.

7. The composition of claim 1, wherein the stable solubility is for at least 5 days after mixing into solution.

8. The composition of claim 1, wherein the stable solubility is for at least 6 days after mixing into solution.

9. The composition of claim 1, wherein the stable solubility is for at least 7 days after mixing into solution.

10. The composition of claim 1, wherein the stable solubility is for at least 8 days after mixing into solution.

11. The composition of claim 1, wherein the stable solubility is for at least 9 days after mixing into solution.

12. The composition of any of claims 1-11, wherein the stable solubility is up to 9 days after mixing into solution.

13. The composition of any of claims 1-12, further comprising 0.01 gm to 5 gm of cellulose and / or cellulose derivative per gram of Florfenicol.

14. The composition of any of claims 1-13, further comprising povidone of 5 % (wt / vol) to 40 % (wt / vol).

15. The composition of any of claims 1-14, further comprising an NSAID16. The composition of claim 15, wherein the NSAID includes meloxicam.

17. The composition of any of claims 1-16, further comprising a chelator agent.

18. The composition of claim 17, wherein the chelator agent includes EDTA.

19. A method of treatment for infection and inflammation, comprising: obtaining the composition according to any of claims 1-18; and providing the composition to an animal for drinking.

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