Delayed release pharmaceutical formulations

Abstract

Delivery of a drug is controlled to impart a delay before release after administration by formulating the drug with a disruption agent to provide a core, and coating the core with a regulatory membrane comprising a water-soluble gel-forming polymer and a water-insoluble film-forming polymer.

1 . A delayed release pharmaceutical composition comprising a core which includes a drug and a disruption agent and further comprising a regulatory membrane coating on the core formed from a mixture of a water-soluble gel-forming polymer and a water-insoluble film-forming polymer.  
     
     
         2 . A composition according to  claim 1 , wherein the disruption agent is selected from polymers with the capacity to expand on hydration and compounds which can generate an internal osmotic pressure within the membrane.  
     
     
         3 . A composition according to  claim 2 , wherein the disruption agent is one or more of a low substituted hydroxypropylcellulose, sodium starch glycolate, sodium carboxymethylcellulose, croscarmellose sodium or carbomer.  
     
     
         4 . A composition according to  claim 2 , wherein the disruption agent is one or more electrolytes, sugars or polyhydric alcohols.  
     
     
         5 . A composition according to any preceding claim, wherein the core includes one or more excipients.  
     
     
         6 . A composition according to  claim 5 , wherein the core is a spheroid and includes a spheronisation aid.  
     
     
         7 . A composition according to  claim 6 , wherein the spheronisation aid is microcrystalline cellulose.  
     
     
         8 . A composition according to  claim 6  or  7 , wherein the spheroid further includes a binder.  
     
     
         9 . A composition according to  claim 8 , wherein the binder is hydroxypropylmethylcellulose.  
     
     
         10 . A composition according to any preceding claim, wherein the amount of drug is 0.1 to 500 mg.  
     
     
         11 . A composition according to any preceding claim, wherein the water-soluble gel-forming polymer of the regulatory membrane coating is a high viscosity grade hydroxyalkylcellulose or methyl cellulose.  
     
     
         12 . A composition according to  claim 11 , wherein the hydroxyalkylcellulose is hydroxypropylmethylcellulose.  
     
     
         13 . A composition according to any preceding claim, wherein the water-insoluble film forming polymer of the regulatory membrane coating is an alkyl cellulose.  
     
     
         14 . A composition according to  claim 13 , wherein the alkyl cellulose is ethyl cellulose.  
     
     
         15 . A composition according to any preceding claim, which releases substantially no drug in the delay period of up to 1 to 6 hours.  
     
     
         16 . A composition according to  claim 15 , wherein the delay period is 1 to 2 hours.  
     
     
         17 . A composition according to any preceding claim, which after the delay period releases substantially the entire content of the drug over a release period of not greater than 6 hours.  
     
     
         18 . A composition according to any of  claims 1  to  16 , which after the delay period releases substantially the entire content of the drug by a controlled release over 1 to 12 hours.  
     
     
         19 . A composition according to any preceding claim, wherein the drug is selected from the group consisting of hypnotics, anti-inflammatories, steroids, anthelmintics, antifungals, anti-cancers, proteins and peptides, semicarbazones, H2-blockers, asthmatic drugs, beta-blockers, calcium channel blockers, NSAIDs, and anti-emetic drugs.  
     
     
         20 . A composition according to any preceding claim, which is a unitary dosage form.  
     
     
         21 . A composition according to any of  claims 1  to  19 , which is a multi-unit dosage form.  
     
     
         22 . A method for preparing a composition according to any preceding claim, which comprises coating a core containing a mixture of a drug and disruption agent with a mixture of a water-soluble gel-forming polymer and a water-insoluble film forming polymer.  
     
     
         23 . A method for controlling delivery of a drug to impart a delay before release after adminstration, which comprises formulating the drug with a disruption agent to provide a core, and coating the core with a regulatory membrane comprising a water-soluble gel-forming polymer and a water-insoluble film-forming polymer.