Film dosage form with extended release mucoadhesive particles

Abstract

An orally administered dosage form that facilitates delivery of an agent locally in the buccal cavity for a sustained period of time includes mucoadhesive particles that are made of at least a mucoadhesive material combined with the agent, and which are dispersed in a disintegrating film. The dosage form is capable of delivering an agent to a patient at the desired oral mucosa site over an extended period of time while reducing patient discomfort or annoyance associated with conventional sustained release mucoadhesive films that must reside on the oral mucosa during the period of sustained release.

1 . An oral dosage form comprising:
 (a) a disintegrable film that breaks up into particles and/or dissolves in less than 5 minutes after oral administration to a subject; and   (b) bioadhesive particles dispersed in the disintegrable film, the bioadhesive particles comprising a bioadhesive material exhibiting adhesivity to targeted mucosa, an active agent, and a penetration enhancer that increases permeation of the active agent through epithelium of the targeted mucosa.   
     
     
         2 . The oral dosage form of  claim 1 , wherein the bioadhesive particles have an erosion time within which 90% of the mucoadhesive material is dissolved that is from 5 to 5000 times the disintegrating time within which 90% of the film is disintegrated. 
     
     
         3 . The oral dosage form of  claim 1 , wherein the 90% erosion time is more than 100 times the 90% disintegrating time. 
     
     
         4 . The oral dosage form of  claim 1 , wherein the mucoadhesive material is taken from the group consisting of chitosan, polyvinyl pyrrolidone, alginate, polycarbophil, pectin, hyaluronic acid and esters thereof, agar agarose, dextran, ovalbumin, collagen, casein. 
     
     
         5 . The oral dosage form of  claim 1 , wherein the mucoadhesive material is taken from the group consisting of polysaccharides, proteins, polyhydroxyalkanoates (PHA), polyhydroxybutyrate (PHB), polyhydroxybutyrate co-hydroxyvalerate (PHBV), polylactides, and polycaprolactones. 
     
     
         6 . The oral dosage form of  claim 1 , having a drug concentration ranging between about 0.1 to about 20%. 
     
     
         7 . The oral dosage form of  claim 1 , wherein the mucoadhesive particles have sizes of between about 100 nm and about 100 micrometers. 
     
     
         8 . The oral dosage form of  claim 1 , wherein the mucoadhesive particles have sizes of between about 1.0 μm to about 10.0 μm diameter for mucosal uptake delivery. 
     
     
         9 . The oral dosage form of  claim 1 , wherein the weight ratio of film/particles is in the range of from 5 to 75. 
     
     
         10 . The oral dosage form of  claim 1 , wherein the weight ratio of film/particles in in the range of from 10 to 50. 
     
     
         11 . An oral dosage form comprising:
 (a) a disintegrable film that breaks up into particles and/or dissolves in less than 5 minutes after oral administration to a subject; and   (b) bioadhesive particles dispersed in the disintegrable film, the bioadhesive particles comprising a bioadhesive copolymer of glycolide-based monomers and an active agent.   
     
     
         12 . The oral dosage form of  claim 11 , in which the bioadhesive particles further comprise a penetration enhancer that increases permeation of the active agent through epithelium of the targeted mucosa. 
     
     
         13 . The oral dosage form of  claim 12 , wherein the bioadhesive particles have an erosion time within which 90% of the mucoadhesive material is dissolved that is from 5 to 5000 times the disintegrating time within which 90% of the film is disintegrated. 
     
     
         14 . The oral dosage form of  claim 13 , wherein the 90% erosion time is more than 100 times the 90% disintegration time. 
     
     
         15 . The oral dosage form of  claim 11 , having a drug concentration ranging between about 0.1 to about 20%. 
     
     
         16 . The oral dosage form of  claim 11 , wherein the mucoadhesive particles have sizes of between about 100 nm and about 100 micrometers. 
     
     
         17 . The oral dosage form of  claim 11 , wherein the mucoadhesive particles have sizes of between about 1.0 μm to about 10.0 μm diameter for mucosal uptake delivery. 
     
     
         18 . The oral dosage form of  claim 11 , wherein the weight ratio of film/particles is in the range of from 5 to 75. 
     
     
         19 . The oral dosage form of  claim 11 , wherein the weight ratio of film/particles is in the range of from 10 to 50. 
     
     
         20 . An oral dosage form comprising:
 (a) a disintegrable film that breaks up into particles and/or dissolves in less than 5 minutes after oral administration to a subject; and   (b) bioadhesive particles dispersed in the disintegrable film, the bioadhesive particles comprising a bioadhesive material exhibiting adhesivity to targeted mucosa, THC or dronabinol, and a penetration enhancer that increases permeation of the THC or dronabinol through epithelium of the targeted mucosa.   
     
     
         21 . An oral dosage form comprising:
 (a) a disintegrable film that breaks up into particles and/or dissolves in less than 5 minutes after oral administration to a subject; and   (b) bioadhesive particles dispersed in the disintegrable film, the bioadhesive particles comprising a bioadhesive material exhibiting adhesivity to targeted mucosa, an active agent, and a penetration enhancer that increases permeation of the active agent through epithelium of the targeted mucosa,
 wherein the bioadhesive particles are prepared by an emulsion technique. 
   
     
     
         22 . The oral dosage form of  claim 21 , wherein the active agent is encapsulated in the bioadhesive particles. 
     
     
         23 . The oral dosage form of  claim 21 , wherein the active agent and the permeation enhancer are together encapsulated in the bioadhesive particles.