unless otherwise indicated , all ingredient concentrations are listed as weight volume ( w / v ) percentages (%). the amount of fluoroquinolone drug included in the compositions of the present invention can be any amount that is therapeutically effective and will depend upon a number of factors , including the identity and potency of the chosen drug . the total concentration of fluoroquinolone drug in the composition will generally be about 1 . 5 % or less . in topically administrable ophthalmic compositions , the typical concentration of fluoroquinolone drug ( e . g ., moxifloxacin ) will be at least about 0 . 2 %, more typically at least about 0 . 4 % and possibly at least about 0 . 5 % but will typically be less than about 2 . 0 % more typically less than about 1 . 0 % and still more typically less than about 0 . 7 %. potentially suitable fluoroquinolones include , without limitation , ciprofloxacin , moxifloxacin , levofloxacin , enrofloxacin , ofloxacin , gatifloxacin and norfloxacin . the fluoroquinolone drug can include a single fluoroquinolone or a combination of multiple different fluoroquinolones . further , it shall be understood that , for the present invention , the naming of a particular fluoroquinolone is considered to include salts and derivatives of that fluoroquinolone , unless otherwise specifically stated . for example , the name moxifloxacin is meant to include moxifloxacin , moxifloxacin hcl and derivatives of moxifloxacin . moxifloxacin is a particularly preferred fluoroquinolone drug . thus , in a preferred embodiment , the fluoroquinolone drug can be at least 50 %, more typically at least 70 % and even more typically at least 90 % by weight moxifloxacin . of course , in this embodiment , the fluoroquinolone drug can be substantially entirely or entirely moxifloxacin . as use herein , the term substantially as it is used to modify terms such as entirely is intended to mean all but a nominal amount . the composition and / or vehicles of the present invention also typically include viscosity enhancing agent . various ingredients , particularly polymer or hydrocarbons , can be employed for the viscosity enhancing agent and the viscosity enhancing agent can include one or multiple ingredients . the viscosity enhancing agent is typically at least 0 . 1 %, more typically at least 0 . 3 % and even more typically at least 0 . 6 % of the composition and / or vehicle of the present invention . the viscosity enhancing agent is typically less than 4 . 0 %, more typically less than 1 . 2 % and even more typically less than 0 . 75 % of the composition and / or vehicle of the present invention . polysaccharide and particularly xanthan gum is desirable as the viscosity enhancing agent . thus , in a preferred embodiment , the viscosity enhancing agent can be at least 50 %, more typically at least 70 % and even more typically at least 90 % by weight polysaccharide and , more particularly , xanthan gum . of course , in this embodiment , the viscosity enhancing agent can be substantially entirely or entirely polysaccharide and , in particular , xanthan gum . xanthan gum is generally available in at least two grades from some commercial suppliers , a food or industrial grade and a pharmaceutical grade . when used , it is preferable to polish filter even pharmaceutical grade materials so that the finished pharmaceutical product will have increased clarity . as one skilled in the art appreciates , the appropriate filter size for polish filtration depends upon the size of the undesired impurities contained in raw material . for example , in the case of a solution composition , it has been found that the rhodigel clear grade of xanthan gum from rhone - poulenc inc . should be filtered through a 0 . 45 μm filter in order to remove cell debris and impurities . multiple stages of filters can be used to increase the overall efficiency of the polish filtration process . the composition and / or vehicle of the present invention can also include an antimicrobial system such as a borate / polyol complex system . an example of one potentially suitable system is discussed in u . s . pat . no . 6 , 143 , 799 , which is incorporated herein by reference for all purposes . as used herein , the term “ borate ” shall refer to boric acid , salts of boric acid , borate derivatives and other pharmaceutically acceptable borates , or combinations thereof . most suitable are : boric acid , sodium borate , potassium borate , calcium borate , magnesium borate , manganese borate , and other such borate salts . borate interacts with polyols , such as glycerol , propylene glycol , sorbitol and mannitol , to form borate polyol complexes . the type and ratio of such complexes depends on the number of oh groups of a polyol on adjacent carbon atoms that are not in trans configuration relative to each other . it shall be understood that weight / volume percentages of the ingredients polyol and borate include those amounts whether as part of a complex or not . as used herein , the term “ polyol ” includes any compound having at least one hydroxyl group on each of two adjacent carbon atoms that are not in trans configuration relative to each other . the polyols can be linear or cyclic , substituted or unsubstituted , or mixtures thereof , so long as the resultant complex is water soluble and pharmaceutically acceptable . examples of such compounds include : sugars , sugar alcohols , sugar acids and uronic acids . preferred polyols are sugars , sugar alcohols and sugar acids , including , but not limited to : mannitol , glycerin , xylitol , sorbitol and propylene glycol . in one embodiment , the polyol of the borate / polyol system is at least 70 % by weight , more particularly at least 90 % by weight , substantially entirely or entirely mannitol , sorbitol or a combination thereof . when used , the borate / polyol complex antimicrobial system ( i . e ., the borate and polyol together ) is typically at least 0 . 03 w / v %, more typically at least 0 . 2 w / v % and even possibly at least 0 . 5 w / v % of the composition , the vehicle or both . when used , the borate / polyol complex antimicrobial system is typically less than 3 w / v %, more typically less than 1 w / v % and even possibly less than 0 . 7 w / v % of the vehicle , the composition or both . the compositions and / or vehicles of the present invention typically include halide and , more particularly non - hydrogen halide salt that preferably improves clarity of the composition and / or vehicle . as used herein , non - hydrogen halides include all halides with the exception of hydrogen halides such hydrogen chloride ( hcl ) where hydrogen provide the positive charge of the halide that matches the negative charge of the halogen . it is contemplated that the non - hydrogen halide or halide salt may include a single halide or may be composed of multiple different halides . the non - hydrogen halide or halide salt is typically at least 0 . 1 w / v %, more typically at least 0 . 4 w / v % and even possibly at least 0 . 5 w / v % and even more possibly at least 0 . 65 w / v % of the composition , the vehicle or both . the halide or halide salt is typically less than 3 w / v %, more typically less than 1 . 5 w / v % and even possibly less than 1 . 0 w / v % of the vehicle , the composition or both . suitable non - hydrogen halides ( e . g ., halide salts ) include , without limitation , sodium chloride , potassium chloride , calcium chloride , combinations thereof or the like . while it is contemplated that the non - hydrogen halide of the present invention can be formed of multiple different ingredients , it has advantageously been found that sodium chloride ( nacl ) alone or substantially alone can provide a highly desired reduction in nephelos or turbidity of the composition and / or vehicle without the need for other non - hydrogen halides . thus , it is contemplated that the composition and / or vehicle of the present invention is entirely or substantially free of any non - hydrogen halide other than nacl . to achieve desirably low levels of turbidity , it is preferable to have particular ratios for the w / v % of non - hydrogen halide in the composition relative to w / v % of fluoroquinolone drug in the composition . such ratio is typically between 0 . 7 and 2 . 2 , more typically between 1 . 0 and 1 . 7 and still more typically between 1 . 1 and 1 . 4 . these ratios have been shown to be of particular importance for the combination of moxifloxacin with nacl in the presence of xanthan gum . the turbidity of the composition , the vehicle or both is desirably low when measured in nephelometric turbidity units ( ntus ) according to european standard en iso 7027 : 1999 . the turbidity of the composition , the vehicle or both is typically less than 20 ntu , more typically less than 13 ntu , still more typically less than 10 ntu and even possibly less than 8 ntu . visual clarity is preferably less than or equal to (≦) piii , more preferably ≦ pii and still more preferably ≦ pi according to chapter 2 . 2 . 1 of the european pharmacopeia , 6 th edition . the composition and / or vehicle solubility of the present invention can include surfactant or other appropriate co - solvent . the surfactant may be nonionic , anionic , cationic , amphoteric , or amphiphilic . exemplary nonionic surfactants or co - solvents include tyloxapol , polyoxyethylene sorbitan esters , polyethoxylated castor oils , polyethoxylated hydrogenated castor oils such as hco - 40 , poloxamers , polyoxyethylene / polyoxypropylene surfactants , polyoxyethylene lauryl ether , polyoxyethylene stearate , polyoxyethylene propylene glycol stearate , hydroxyalkylphosphonate , a combination thereof , or other agents known to those skilled in the art . the surfactant , when included , is typically at least 0 . 005 w / v %, more typically at least 0 . 02 w / v % and even possibly at least 0 . 04 w / v % of the composition , the vehicle or both . the surfactant , when included , is also typically less than 1 w / v %, more typically less than 0 . 1 w / v % and even possibly less than 0 . 07 w / v % of the vehicle , the composition or both . polyether alcohol ( e . g ., alkyl aryl polyether alcohol ) surfactants have been found to be particularly useful in the vehicles and compositions of the present invention . such surfactants have been found to assist in dispersing the fluoroquinolone drug , particularly moxifloxacin , throughout the composition such that the overall composition has greater homogeneity . this is particularly important when the composition is a multi - dose solution ( e . g ., ophthalmic solution ) that is located within a container ( e . g ., a dropper ) and is administered in drop form . the greater homogeneity can provide for more uniform amounts of drug to be administered in each drop . this is particularly the case where the surfactant promotes homogeneity in the tip of the dropper and it has been found that the surfactants discussed herein , particularly alkyl aryl polyether alcohol such as tyloxapol , have been found to facilitate greater homogeneity at the dropper tips . thus , it is contemplated that the surfactant can be at least 50 %, more typically at least 70 % and even more typically at least 90 % by weight polyether alcohol ( e . g ., alkyl aryl polyether alcohol such as tyloxapol ). of course , in this embodiment , the surfactant can be substantially entirely or entirely polyether alcohol ( e . g ., alkyl aryl polyether alcohol such as tyloxapol ). in addition to the ingredients above , it is contemplated that a variety of additional or alternative ingredients may be employed in the compositions or vehicles of the present invention . other additional therapeutic agents , antimicrobials , suspension agents or the like may be included . other exemplary ingredients possible for the composition or vehicle include , without limitation , tonicity agents , buffering agents , anti - oxidants , combinations thereof or the like . water will make up a substantial portion of the aqueous solutions as will become apparent from the examples below . hydrochloric acid , sodium hydroxide or other acids or bases may be used to adjust ph . the ingredients described herein may be used in forming various types of pharmaceutical compositions or vehicles such as ophthalmic , otic , nasal and dermatological compositions or vehicles , but are particularly useful for ophthalmic solutions , which are typically aqueous . examples of such solutions include , without limitation , ophthalmic pharmaceutical topical solutions that can be used in the treatment of glaucoma , dry eye , infections , allergies or inflammation ( e . g ., conjunctivitis ); solutions for enhancing the ocular comfort of patients ; and various other types of ophthalmic solutions , such as ocular lubricating products , artificial tears , astringents , and so on . the compositions or vehicles of the present invention are typically formulated so as to be compatible with the eye and / or other tissues to be treated therewith . the ophthalmic compositions or vehicles intended for direct application to the eye will be formulated so as to have a ph and tonicity that are compatible with the eye . the compositions will typically have a ph in the range of 4 to 9 , preferably 5 . 5 to 8 . 5 , and most preferably 5 . 5 to 8 . 0 . particularly desired ph ranges are 6 . 0 to 7 . 8 and more specifically 6 . 4 or even 6 . 7 to 7 . 5 or even 7 . 2 . the compositions will have an osmolality of 200 to 400 or 450 milliosmoles per kilogram ( mosm / kg ), more preferably 240 to 360 mosm / kg . it is typically preferable for , the compositions or vehicles of the present invention to have sufficient antimicrobial activity to allow them to satisfy the certain preservative efficacy requirements , particularly usp preservative efficacy requirements and / or ph . eur . b . the preservative efficacy standards for multi - dose ophthalmic solutions in the u . s . and other countries / regions are set forth in the following table : preservative efficacy test (“ pet ”) criteria ( log order reduction of microbial inoculum over time 1 there are two preservative efficacy standards in the european pharmacopoeia “ a ” and “ b ”. the standards identified above for the usp 27 are substantially identical to the requirements set forth in prior editions of the usp , particularly usp 24 , usp 25 and usp 26 . in at least several embodiments of the present invention , it has been found that the overall composition or vehicle can provide a desired bioavailability without the need for inclusion of additional ingredients . thus , it is contemplated that the vehicle may consist or consist essentially of only the following : viscosity enhancing agent ; borate / polyol system ; surfactant ; non - hydrogen halide ; sodium hydroxide or hydrochloric acid ; and water or any combination thereof as those ingredients are described herein . further it is contemplated in such embodiment that the composition may consist of or consist essentially of only the following : fluoroquinolone drug ; viscosity enhancing agent ; borate / polyol system ; surfactant ; non - hydrogen halide ; sodium hydroxide or hydrochloric acid ; and water or any combination thereof as those ingredients are described herein . the following examples are presented to illustrate further various aspects of the present invention , but are not intended to limit the scope of the invention in any respect . each of the formulations shown in tables 1 and 2 below was prepared as follows . xanthan gum stock solution was prepared and clarified through 1 . 2 and 4 . 5 μm filters . sodium chloride was added to and dissolved in the xanthan gum to form a xanthan gum solution . if present , boric acid , sorbitol , tyloxapol and moxifloxacin were combined with purified water to form a second solution . all ingredients of the second solution were dissolved by stirring and ph was adjusted by adding naoh or hcl . then the second solution was added into the xanthan gum solution and the formulation was mixed by stirring until obtaining a substantially homogeneous solution . purified water was added up to final volume to form the final solution , which was mixed again by stirring . the final solution was then autoclaved at 124 ° c . for 40 minutes . the sterilized final solution was then cooled to room temperature . if necessary , ph was adjusted again by adding naoh or hcl and sterilized purified water is added up to final volume . the final solution was mixed by stirring to homogenize . it has also been found that compositions of the present invention provide higher concentrations of fluoroquinolone drug , particularly moxifloxacin to a biological target ( e . g ., the eye ) at later times after administering the composition to the target . for example , a composition substantially identical to composition h from table 2 was applied to the eyes of rabbits and the following concentrations were observed in the aqueous humor and tear film of the eyes of those rabbits : advantageously , these concentrations , particularly after the passing of the 5 minute , 10 minute , 15 minute , 30 minute and 60 minute time intervals , are at least double , triple , 5 × or even 8 × the concentrations of moxifloxacin composition currently commercially available . aqueous humor concentrations of moxifloxacin in micrograms per milliliter ( μg / ml ) in human eyes at each of 5 collection times are presented in table 3 below and are graphically shown in fig1 . in particular , the table and graph show mean concentrations in the aqueous humor after a single topical dose of a moxifloxacin composition according to the present invention ( composition h from above ) and after a single topical dose of a commercially available moxifloxacin composition that is available under the tradename vigamox ® from alcon laboratories , fort worth , tex ., 76134 . composition z is represented by vigamox ®, in addition to moxifloxacin hydrochloride , includes boric acid , sodium chloride , and purified water and may also contain hydrochloric acid / sodium hydroxide to adjust ph to approximately 6 . 8 . aqueous humor concentrations of moxifloxacin in micrograms per milliliter ( μg / ml ) in human eyes at each of 5 collection times are also presented in table 4 below and are graphically shown in fig2 . in particular , the table and graph show mean concentrations in the conjunctival tissue after a single topical dose of composition h and after a single topical dose of vigamox ®. as can be seen from tables 3 and 4 and fig1 and 2 , the compositions of the present invention can provide significantly higher concentrations of moxifloxacin to the aqueous humor and the conjunctival tissue of the human eye . the invention has been described by reference to certain preferred embodiments ; however , it should be understood that it may be embodied in other specific forms or variations thereof without departing from its spirit or essential characteristics . the embodiments described above are therefore considered to be illustrative in all respects and not restrictive , the scope of the invention being indicated by the appended claims rather than by the foregoing description .
pharmaceutical compositions containing a fluoroquinolone antibiotic drug are disclosed . the compositions exhibit improved homogeneity , improved bioavailability , lower turbidity or a combination thereof . the composition can be use as otic or nasal compositions , but are particularly useful as ophthalmic compositions .