Aqueous suspension preparations

Abstract

Addition of polyvinylpyrrolidone and a water-soluble anionic macromolecular compound to an aqueous suspension of a hardly soluble drug allows to provide an aqueous suspension in which aggregation of drug particles, formation of macro crystals from suspended particles and formation of secondary particles from deposited particles are prevented, and adhesion and adsorption to containers made of plastics, e.g., polypropylene or polyethylene, are avoided. As it has a good redispersibility, the aqueous suspension is useful as eye drops, nasal drops, ear drops, injections, oral preparations, liniments and lotions.

1 . An aqueous suspension comprising a hardly soluble drug, polyvinylpyrrolidone and a water-soluble anionic macromolecular compound.  
     
     
         2 . The aqueous suspension according to  claim 1 , wherein the lower and the upper limit concentrations of polyvinylpyrrolidone are about 0.1 w/v % and about 10 w/v %, respectively, and the lower and the upper limit concentrations of the water-soluble anionic macromolecular compound are about 0.05 w/v % and about 1.0 w/v %, respectively.  
     
     
         3 . The aqueous suspension according to  claim 1 , wherein the concentration of polyvinylpyrrolidone is 0.1-5.0 w/v % and the water-soluble anionic macromolecular compound is contained at a weight ratio of 0.1-2.0 to the amount of polyvinylpyrrolidone.  
     
     
         4 . The aqueous suspension according to  claim 2  or  3 , wherein the hardly soluble drug is at least one selected from steroidal antiinflammatory drugs, antiphlogistic-analgesics, chemotherapeutics, synthetic antimicrobials, antivirals, hormones, anti-cataract drugs, neovascularization suppressants, immunosuppressants, protease inhibitors, aldose reductase inhibitors, antiallergics, anxiolytics, antipsychotics, antibiotics, antitumor drugs, anti-hyperlipemic drugs, antitussive-expectorants, muscle relaxants, antiepileptics, antiulcer drugs, antidepressants, cardiotonics, antiarrhythmic drugs, vasodilators, antihypertensive-diuretics, antidiabetics, antituberculosis drugs, narcotic antagonists, drugs for dermatologic diseases and diagnostic drugs.  
     
     
         5 . The aqueous suspension according to  claim 4 , wherein the hardly soluble drug is a steroidal antiinflammatory drug.  
     
     
         6 . The aqueous suspension according to  claim 5 , wherein the steroidal antiinflammatory drug is at least one selected from cortisone acetate, hydrocortisone acetate, betamethasone, prednisolone, fluticasone propionate, dexamethasone, triamcinolone, loteprednol, fluorometholone, difluprednate, momethasone furoate, clobetasol propionate, diflorasone diacetate, diflucortolone valerate, fluocinonide, amcinonide, halcinonide, fluocinolone acetonide, triamcinolone acetonide, flumethasone pivalate and clobetasone acetate.  
     
     
         7 . The aqueous suspension according to  claim 4 , wherein the hardly soluble drug is an anti-cataract drug.  
     
     
         8 . The aqueous suspension according to  claim 7 , wherein the anti-cataract drug is pirenoxine or N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal.  
     
     
         9 . The aqueous suspension according to  claim 4 , wherein the hardly soluble drug is an antiphlogistic-analgesic.  
     
     
         10 . The aqueous suspension according to  claim 9 , wherein the antiphlogistic-analgesic is at least one selected from alclofenac, alminoprofen, indomethacin, epirizole, oxaprozin, ketoprofen, diclofenac sodium, diflunisal, naproxen, piroxicam, fenbufen, flufenamic acid, flurbiprofen, floctafenine, pentazocine, metiazinic acid, mefenamic acid, mofezolac, salicylic acid, sulpyrine, atropine, scopolamine, morphine, pethidine, levorphanol, oxymorphone and salts thereof.  
     
     
         11 . The aqueous suspension according to one of claims  1 - 10 , wherein the water-soluble anionic macromolecular compound is at least one selected from anionic polysaccharides, anionic polyvinyl-based polymers and anionic macromolecular polypeptides.  
     
     
         12 . The aqueous suspension according to  claim 11 , wherein the anionic polysaccharide is at least one selected from carboxymethylcellulose or a salt thereof, alginic acid or a salt thereof, chondroitin sulfate or a salt thereof, pectin and xanthan gum.  
     
     
         13 . An aqueous suspension comprising a steroidal antiinflammatory drug, polyvinylpyrrolidone and alginic acid or a salt thereof.  
     
     
         14 . The aqueous suspension according to  claim 13 , wherein the lower and the upper limit concentrations of polyvinylpyrrolidone are about 0.1 w/v % and about 10 w/v %, respectively, and the lower and the upper limit concentrations of alginic acid or a salt thereof are about 0.05 w/v % and about 1.0 w/v %, respectively.  
     
     
         15 . An aqueous suspension comprising an anti-cataract drug, polyvinylpyrrolidone and alginic acid or a salt thereof.  
     
     
         16 . The aqueous suspension according to  claim 15 , wherein the lower and the upper concentrations of polyvinylpyrrolidone are about 0.1 w/v % and about 10 w/v %, respectively, and the lower and the upper limit concentrations of alginic acid or a salt thereof are about 0.05 w/v % and about 1.0 w/v %, respectively.  
     
     
         17 . The aqueous suspension according to  claim 16 , wherein the anti-cataract drug is pirenoxine.  
     
     
         18 . An aqueous suspension comprising an antiphlogistic-analgesic, polyvinylpyrrolidone and alginic acid or a salt thereof.  
     
     
         19 . The aqueous suspension according to  claim 18 , wherein the lower and the upper concentrations of polyvinylpyrrolidone are about 0.1 w/v % and about 10 w/v %, respectively, and the lower and the upper limit concentrations of alginic acid or a salt thereof are about 0.2 w/v % and about 1.0 w/v %, respectively.  
     
     
         20 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of eye drops.  
     
     
         21 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of nasal drops.  
     
     
         22 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of ear drops.  
     
     
         23 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of an injection.  
     
     
         24 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of an oral preparation.  
     
     
         25 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of a liniment.  
     
     
         26 . The aqueous suspension according to one of claims  1 - 19 , wherein the aqueous suspension is in the form of a lotion.  
     
     
         27 . A method for improving the redispersibility of an aqueous suspension of a hardly soluble drug comprising addition of polyvinylpyrrolidone and a water-soluble anionic macromolecular compound to the aqueous suspension.  
     
     
         28 . The method according to  claim 27 , wherein the lower and the upper concentrations of polyvinylpyrrolidone are about 0.1 w/v % and about 10 w/v %, respectively, and the lower and the upper limit concentrations of the water-soluble anionic macromolecular compound are about 0.05 w/v % and about 1.0 w/v %, respectively.  
     
     
         29 . The method according to  claim 27 , wherein the concentration of polyvinylpyrrolidone is 0.1-5.0 w/v % and the water-soluble anionic macromolecular compound is contained at a weight ratio of 0.1-2.0 to the amount of polyvinylpyrrolidone.