Phenylephrine pharmaceutical formulations and compositions for colonic abosorption

Abstract

The invention discloses a pharmaceutical composition comprising phenylephrine or a pharmaceutically acceptable salt thereof and an erodible layer which is for oral administration wherein the composition delivers phenylephrine or a pharmaceutically acceptable salt thereof via absorption in the colon. The pharmaceutical composition comprises a core comprising phenylephrine or a pharmaceutically acceptable salt thereof and an erodible layer which is in a time-dependent, pH-dependent, or colon-specific enzyme-dependent erodible layer that degrades to expose the core to release phenylephrine in the colon. In one preferred embodiment, the erodible layer encases the core. The composition optionally further comprises phenylephrine in the erodible layer or other additional layer(s). The pharmaceutical composition can further comprise one or more additional therapeutically active agents selected from one or more of the group consisting of antihistamines, analgesics, anti-pyretics, and non-steroidal anti-inflammatory agents. The invention also discloses methods of administering phenylephrine via the colon, thereby increasing the bioavailable amount of therapeutically active unconjugated phenylephrine relative to the total phenylephrine in the plasma.

1 . A pharmaceutical composition suitable for oral administration, wherein the composition comprises:
 a) a core comprising phenylephrine or a pharmaceutically acceptable salt thereof; and   b) an erodible layer, optionally comprising phenylephrine or a pharmaceutically acceptable salt thereof;   wherein upon ingestion of the composition by a subject at least a portion of phenylephrine is absorbed in the colon of the subject.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein at least 5% by weight of phenylephrine or a pharmaceutically acceptable salt thereof is absorbed in the colon of the subject. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . The pharmaceutical composition according to claim  5 , wherein the erodible pellet coating comprises a pH-sensitive polymer or a colon-specific polymer. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the core further comprises a penetration enhancer. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The pharmaceutical composition according to  claim 1 , wherein the erodible layer comprises a mixture of hydroxypropyl methylcellulose, polyvinyl alcohol, or polyvinyl alcohol-polyethylene glycol graft copolymer and carboxymethyl cellulose or carboxymethyl cellulose sodium salt. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the erodile layer further comprises microcrystalline cellulose. 
     
     
         12 - 18 . (canceled) 
     
     
         19 . The composition according to  claim 1 , further comprising one or more additional therapeutic agent(s). 
     
     
         20 - 30 . (canceled) 
     
     
         31 . A pharmaceutical composition for oral administration, wherein the composition comprises:
 a) a core comprising phenylephrine or a pharmaceutically acceptable salt thereof; and   b) a pH-sensitive layer
 wherein the pH-sensitive layer erodes to expose the core at least 5 hours after ingestion of the composition by a subject, and 
 wherein the pH-sensitive layer completely disintegrates under a pH condition in the colon. 
   
     
     
         32 . The composition according to  claim 31 , wherein the pH condition is from about pH 5.5 to about pH 7.0. 
     
     
         33 - 52 . (canceled) 
     
     
         53 . A pharmaceutical composition suitable for oral administration to deliver phenylephrine or a pharmaceutically acceptable salt thereof in a single dose, to a subject in need thereof, wherein unmetabolized phenylephrine is detectable in plasma of said subject for at least 5 hours after ingestion of the composition by the subject. 
     
     
         54 . The pharmaceutical composition of  claim 53 , wherein unmetabolized phenylephrine is detectable in plasma of said subject for at least 6 hours after ingestion of the composition by the subject. 
     
     
         55 - 59 . (canceled) 
     
     
         60 . The pharmaceutical composition of  claim 53 , wherein the composition is formulated to deliver at least a portion of phenylephrine or a pharmaceutically acceptable salt thereof to the colon of the subject. 
     
     
         61 . The pharmaceutical composition of  claim 53 , wherein the composition is formulated to also deliver at least a portion of phenylephrine or a pharmaceutically acceptable salt thereof in a sustained release in the upper gastrointestinal system of the subject. 
     
     
         62 . The pharmaceutical composition of  claim 53 , wherein the composition is further formulated to also deliver at least a portion of phenylephrine or a pharmaceutically acceptable salt thereof in an immediate release in the upper gastrointestinal system of the subject. 
     
     
         63 - 67 . (canceled) 
     
     
         68 . The pharmaceutical composition of  claim 1 , wherein
 the core comprises the following components: about 4-5% (w/w) phenylephrine or a pharmaceutically acceptable salt thereof, about 4-5% (w/w) hydroxypropyl cellulose 300-600 cPs at 10%, about 4-5% (w/w) hydroxypropyl cellulose 150-300 cPs at 2%, about 16-17% (w/w) carboxymethylcellulose sodium salt, about 59-61% (w/w) microcrystalline cellulose, and about 0.9-1% (w/w) magnesium stearate; and   the erodible layer comprises the following components: about 1-2% (w/w) phenylephrine or a pharmaceutically acceptable salt thereof, and about 6-10% (w/w) polyvinyl alcohol based polymer.   
     
     
         69 - 70 . (canceled) 
     
     
         71 . The pharmaceutical composition of  claim 1 , wherein the core comprises the following components: about 22.5 mg phenylephrine or a pharmaceutically acceptable salt thereof, about 25 mg hydroxypropyl cellulose 300-600 cPs at 10%, about 25 mg hydroxypropyl cellulose 150-300 cPs at 2%, about 90 mg carboxymethylcellulose sodium salt, about 332.5 mg microcrystalline cellulose, and about 5 mg magnesium stearate. 
     
     
         72 . The pharmaceutical composition of  claim 1 , wherein the erodible layer comprises the following components: about 7.5 mg phenylephrine or a pharmaceutically acceptable salt thereof, and about 36-54 mg polyvinyl alcohol based polymer. 
     
     
         73 . (canceled) 
     
     
         74 . The pharmaceutical composition of  claim 72 , wherein the erodible layer further comprises about 5 mg loratadine or desloratadine. 
     
     
         75 - 90 . (canceled)