Hydrogel-Driven Drug Dosage Form

Abstract

A controlled release dosage form has a coated core with the core comprising a drug-containing composition and a water-swellable composition, each occupying separate regions within the core. The drug-containing composition comprises a low-solubility drug and a drug-entraining agent. The coating around the core is water-permeable, water-insoluble and has at least one delivery port therethrough. A variety of formulations having specific drug release profiles are disclosed.

1 - 131 . (canceled)  
     
     
         132 . A controlled release dosage form comprising a core and a coating around said core wherein: 
 (a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core;    (b) said drug-containing composition comprises a low-solubility drug having a minimum aqueous solubility up to 1 to 2 mg/mL at a pH of 1-8 and a drug-entraining agent, wherein said drug entraining agent is PEO having a molecular weight of at least one of: 
 (i) 500,000 to 800,000 daltons when the weight fraction of said low-solubility drug and said drug-entraining agents is less than about 80% of said drug-containing composition, wherein there is an inverse relationship between the preferred PEO molecular weight and the weight fraction of the drug-containing composition that is said low-solubility drug and said drug-entraining agent; and  
 (ii) 100,000 to 300,000 when the weight fraction of said low-solubility drug and said drug-entraining agents is about 80% or more of said drug-containing composition;  
   wherein the PEO molecular weight may vary higher or lower relative to the above values of molecular weight by 20% to 50%; and    (c) said coating is water-permeable, water-insoluble, and has at least one delivery port therethrough, said coating comprising cellulose acetate (CA) and polyethylene glycol (PEG) having a weight ratio of CA:PEG of from about 6.5:3.5 to about 9:1; and    wherein said drug-containing composition further comprises a concentration-enhancing polymer selected from hydroxypropylmethyl cellulose acetate succinate (HPMCAS), hydroxypropylmethyl cellulose (HPMC), hydroxy propylmethyl cellulose phthalate (HPMCP), cellulose acetate phthalate (CAP) cellulose acetate trimellitate (CAT), and polyvinylpyrrolidone (PVP); and    said drug is not in the form of a solid dispersion.    
     
     
         133 . A dosage form according to  claim 132  wherein said drug-containing composition further comprises an ionic swelling agent selected from sodium croscarmellose and sodium starch glycolate.  
     
     
         134 . A dosage form according to  claim 132  wherein said drug containing composition further comprises a solubilizer.  
     
     
         135 . A dosage form according to  claim 133  wherein said drug containing composition further comprises a solubilizer.  
     
     
         136 . A dosage form according to  claim 134  or  135  wherein said solubilizer is an organic acid, and said drug has enhanced solubility in the presence of said organic acid.  
     
     
         137 . A dosage form according to any one of  claims 132  to  135  wherein said drug-containing composition further comprises a fluidizing agent.  
     
     
         138 . A dosage form according to  claim 137  wherein said fluidizing agent is selected from an organic acid and a sugar.  
     
     
         139 . A dosage form according to  claim 132  wherein said water-swellable composition has a swelling ratio of at least 3.5.  
     
     
         140 . A dosage form according to  claim 132  wherein said coating has a water flux (40/75) of at least 1.0×10 −3  gm/cm 2 .hr.  
     
     
         141 . A dosage form according to  claim 132  wherein said coating is porous with a dry-state density of less than 0.9 times that of the same coating material in nonporous form.  
     
     
         142 . A dosage form according to  claim 132  wherein, following introduction of said dosage form to a use environment, at least about 70 wt % of said drug is released to said use environment within about 12 hours.  
     
     
         143 . A controlled release dosage form according to  claim 132  wherein said drug is an anti-impotence agent.  
     
     
         144 . A controlled release dosage form according to  claim 143  wherein said anti-impotence agent is sildenafil citrate.