Formulations for therapeutic agents absorbed through mucous membranes

Abstract

Particulate crystalline therapeutic substances are formulated with stabilizers to enhance contact between the crystalline therapeutic substances and the mucosal membranes to provide extended therapeutic effect.

What is claimed is:  
     
         1 . A therapeutic formulation comprising: 
 a-of from about 0.1 to about 45% w/v of particles of an poorly water soluble crystalline therapeutic agent having an weight average particle size of less than about 2,000 nm;    b-of from about 0.1 to about 10% w/v of a poloxamer, the poloxamer absorbed on the surface of the particle and having the formula (polyethylene oxide) a -(polypropylene oxide) b -(polyethylene oxide) c  
 wherein 
 a is 46 to 128;  
 b is 16 to 67; and  
 c is 46 to 128; and  
 
   c-water to make 100% w/v.    
     
     
         2 . A therapeutic formulation comprising: 
 a-of from about 0.5% to about 15% w/v of particles of a poorly soluble therapeutic agent, the particles having a weight average particle size of less than about 1,000 nm;    b-of from about 0.25 % to about 5% w/v of a poloxamer, the poloxamer absorbed on the surface of the particle and having the formula    (polyethylene oxide) a -(polypropylene oxide) b -(polyethylene oxide) c  
 wherein 
 a is 46, 52, 62, 75, 97, 98, 122 and 128;  
 b is 16, 30, 35, 39, 47, 54 and 67; and  
 c is 46, 52, 62, 75, 97, 98, 122 and 128; and  
 
   c-water to make 100% w/v.    
     
     
         3 . The particles of  claim 1  wherein said drug substance is selected from analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antiepileptics, antifungal agents, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives, astringents, beta-adrenoceptor blocking agents, cardiac inotropic agents, contrast media, corticosteroids, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin, biphosphonates, protease inhibitors, prostaglandins, radio-pharmaceuticals, sex hormones, steroids, anti-allergic agents, stimulants, sympathomimetics, thyroid agents, vasodilators and xanthines.  
     
     
         4 . The formulation of  claim 1  further comprising up to 1% w/v of a secondary stabilizer selected from the group consisting of dioctylsulfosuccinate and sodium lauryl sulfate.  
     
     
         5 . An orally/rectally administrable gastrointestinal therapeutic formulation comprising: 
 a-of from about 0.1 to about 45% w/v of particles of an poorly water soluble crystalline therapeutic agent having an weight average particle size of less than about 2,000 nm;    b-of from about 0.1 to about 10% w/v of a poloxamer, the poloxamer absorbed on the surface of the particle and having the formula    (polyethylene oxide) a -(polypropylene oxide) b -(polyethylene oxide) c  
 wherein 
 a is 46 to 128;  
 b is 16 to 67; and  
 c is 46 to 128; and  
 
   c-water to make 100% w/v.    
     
     
         6 . The therapeutic formulation of  claim 5  comprising: 
 a-of from about 0.5% to about 15% w/v of particles of a poorly soluble therapeutic agent, the particles having a weight average particle size of less than about 1,000 nm;  
 b-of from about 0.25 % to about 5% w/v of a poloxamer, the poloxamer absorbed on the surface of the particle and having the formula  
 (polyethylene oxide) a -(polypropylene oxide) b -(polyethylene oxide) c  
 wherein 
 a is 46, 52, 62, 75, 97, 98, 122 and 128;  
 b is 16, 30, 35, 39, 47, 54 and 67; and  
 c is 46, 52, 62, 75, 97, 98, 122 and 128; and  
 
 
 c-water to make 100% w/v.  
 
     
     
         7 . The therapeutic formulation of  claim 5  wherein said drug is selected from the group consisting of: antacids, anti-inflammatory agents, antibiotics (including penicillins), antimycobacterial agents, antiviral agents, corticosteroids, parasympathomimetics, radio-pharmaceuticals, sympathomimetics, demulcents, emollients, gastrointestinal protectives and adsorbents, antifungals, H2-blocking agents, proton pump inhibitors, muscarinic antagonists, bismuth compounds, sucralfate, carbenoxolone, prostaglandins, digestants, bile acids, laxatives, antiparasitic agents, anthelmintics, antiprotozoal agents, antimicrobial agents, vitamins, immunologic agents, vaccines, anesthetics, lipid-regulating agents and bile acid sequestrants.