Carbidopa/Levodopa gastroretentive drug delivery

A gastroretentive drug delivery system for the sustained release of an active agent in the gastrointestinal tract, comprising:

• an internal layer having a first side and an opposing second side, said internal layer comprising an active agent and a degradable hydrophilic polymer and a degradable enteric polymer which is substantially insoluble at pH less than 5.5, and a plasticizer, the active agent, the degradable hydrophilic polymer and the degradable enteric polymer being uniformly distributed throughout said internal layer;
• and at least one outer membrane covering said internal layer and comprising at least one polymeric combination of a hydrophilic polymer, a polymer that is insoluble in gastric media, and at least one plasticizer, said at least one outer membrane swelling in the presence of gastric medium,
• wherein one of the materials comprised in said internal layer and one of the materials comprised in said at least one outer membrane are capable of being ultrasonically welded together,
• wherein said at least one outer membrane is directly secured to a side of said internal layer and covers the side of said internal layer to which it is secured, said at least one outer membrane having a length greater than 20 mm in a planar orientation,
• wherein said at least one outer membrane and said internal layer are arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach, said at least one outer membrane permitting passage of gastric fluid from the stomach to said internal layer and permitting passage of gastric fluid and said active agent from said internal layer through said at least one outer membrane to the stomach, and
• wherein said internal layer and said at least one outer membrane secured thereto provide mechanical force sufficient to unfold from the accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric fluid
• with the proviso that a scaffold, containing no active agent, is not present.

A gastroretentive drug delivery system for the sustained release of an active agent in the gastrointestinal tract, comprising:

• an internal layer, including a first side and an opposing second side, comprising an active agent and a degradable hydrophilic polymer which is not instantly soluble in gastric fluid and a degradable enteric polymer which is substantially insoluble at pH less than 5.5, and a plasticizer, the active agent and the degradable hydrophilic polymer and the degradable enteric polymer being uniformly distributed throughout the internal layer, and
• a first and a second outer membrane directly secured to and covering both sides of said internal layer, said first and second outer membranes including at least one polymeric combination of a hydratable swelling polymer and an enteric polymer, and at least one plasticizer, wherein said membranes swell in the presence of gastric fluid,
• wherein one of the materials in said internal layer and one of the materials in each of said first and second outer membranes is capable of being ultrasonically welded together,
• wherein said internal layer and said first and second outer membranes have a length greater than 20 mm in a planar orientation, said internal layer and said outer membranes attached thereto being arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach,
• wherein said internal layer and said first and second outer membranes secured thereto provide sufficient mechanical force to unfold from the accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric fluid,
• wherein said first and second outer membranes have a width and length greater than a width and length of said internal layer, said first and second outer membranes being ultrasonically welded together along the periphery of said first and second outer membranes, said first outer membrane being ultrasonically welded to the first side of said internal layer, and said second outer membrane being ultrasonically welded to the second side of said internal layer, said outer membranes permitting passage of gastric fluid from the stomach to said internal layer and permitting passage of gastric fluid and said active agent from said internal layer through said outer membrane to the stomach, and
• wherein the ultrasonic welds have sufficient mechanical strength to remain intact upon being exposed to gastric medium.

A gastroretentive drug delivery system for the sustained release of an active agent in the stomach and gastrointestinal tract of a patient, comprising:

• an internal layer, including a first side and an opposing second side, comprising a degradable polymer composition, which is not instantly soluble in gastric fluid,
• and an active agent, said active agent and said degradable polymer composition being uniformly distributed throughout the internal layer;
• and
• two outer membranes, each being equal in size with said internal layer, one of said outer membranes being directly secured to and covering the first side of said internal layer and the other of said outer membranes being directly secured to and covering the second side of said internal layer, said two outer membranes each comprising at least one polymeric combination of a hydrophilic polymer and a polymer that is insoluble in gastric media, said outer membranes being hydratable at a rate greater than that of said internal layer and permitting passage of gastric media from the stomach environment to said internal layer and permitting passage of said active agent from said internal layer through said outer membranes to the stomach environment;
• wherein said internal layer and said two outer membranes secured thereto are arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach, and wherein said
• internal layer and said two outer membranes secured thereto provide sufficient mechanical force to unfold from the initial accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric medium.

A gastroretentive drug delivery system for the sustained release of an active agent in the gastrointestinal tract, comprising:

• an internal layer having a first side and an opposing second side, said internal layer comprising an active agent and a degradable hydrophilic polymer and a degradable enteric polymer which is substantially insoluble at pH less than 5.5, and a plasticizer, wherein the active agent and the degradable hydrophilic polymer and the degradable enteric polymer are uniformly distributed throughout said internal layer;
• and
• two outer membranes covering said internal layer, each being equal in size with said internal layer, each said outer membrane comprising at least one polymeric combination of a hydrophilic polymer and a polymer that is insoluble in gastric media, and at least one plasticizer, each said outer membrane configured for swelling in the presence of gastric medium,
• wherein one of the materials comprised in said internal layer and one of the materials comprised in each said outer membrane are capable of being ultrasonically welded together,
• wherein each one of said two outer membranes covers and is directly secured to a different one of said first side and said second side of said internal layer, said two outer membranes having a length greater than 20 mm in a planar orientation,
• wherein said two outer membranes and said internal layer are arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach, said two outer membranes permitting passage of gastric fluid from the stomach to said internal layer and permitting passage of gastric fluid and the active agent from said internal layer through said two outer membranes to the stomach, and
• wherein said internal layer and said two outer membranes secured thereto provide mechanical force sufficient to unfold from the accordion folded figuration to an unfolded configuration having a length of at least b 20 mm within 30 minutes of being exposed to gastric fluid.

A gastroretentive drug delivery system for the sustained release of an active agent in the gastrointestinal tract, comprising:

• an internal layer, including a first side and an opposing second side, comprising an active agent, a degradable hydrophilic polymer which is not instantly soluble in gastric fluid, a degradable enteric polymer which is substantially insoluble at pH less than 5.5, and a plasticizer, the active agent, the degradable hydrophilic polymer and the degradable enteric polymer being uniformly distributed throughout the internal layer;
• and
• first and second outer membranes covering said internal layer and each being equal in size with said internal layer, said outer membranes including at least one polymeric combination of a hydratable swelling polymer, an enteric polymer, and at least one plasticizer, said outer membranes swelling in the presence of gastric fluid, said outer membranes being directly secured to and covering both sides of the internal layer,
• wherein one of the materials in said internal layer and one of the materials in each of said outer membranes are capable of being ultrasonically welded together,
• wherein said internal layer and said first and second outer membranes have a length greater than 20 mm in a planar orientation, said internal layer and said outer membranes attached thereto being arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach,
• wherein said internal layer and said outer membranes secured thereto are capable of providing mechanical force sufficient to unfold from the accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric fluid,
• wherein said first outer membrane is ultrasonically welded to the first side of said internal layer, and said second outer membrane is ultrasonically welded to the second side of said internal layer, said outer membranes permitting passage of gastric fluid from the stomach to said internal layer and permitting passage of gastric fluid and the active agent from said internal layer through said outer membrane to the stomach,
• wherein said internal layer and said first and second outer membranes have a length greater than 20 mm in a planar orientation, said internal layer and said outer membranes attached thereto being arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach, and
• wherein the ultrasonic welds have sufficient mechanical strength to remain intact upon being exposed to gastric medium.

A gastroretentive drug delivery system for the sustained release of an active agent in the stomach and gastrointestinal tract of a patient, comprising:

• an internal layer, including a first side, an opposing second side, and an outer-facing peripheral side extending between respective edges of the first side and the second side, comprising
• a degradable polymer composition, which is not instantly soluble in gastric fluid
• and an active agent, the active agent and the degradable polymer composition being uniformly distributed throughout the internal layer;
• and
• two outer membranes, each being larger in size than said internal layer, one of said outer membranes covering the first side of said internal layer and the other of said outer membranes covering the second side of said internal layer and contacting said peripheral side, said two outer membranes each having a length greater than 20 mm in a planar orientation and each comprising at least one polymeric combination of a hydrophilic polymer and a polymer that is insoluble in gastric media, said outer membranes being hydratable at a rate greater than that of said internal layer and permitting passage of gastric media from the stomach environment to said internal layer and permitting passage of said active agent from said internal layer through said outer membranes to the stomach environment;
• wherein said internal layer and said two outer membranes are arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach, and wherein said
• internal layer and said two outer membranes provide sufficient mechanical force to unfold from the initial accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric medium.

A gastroretentive drug delivery system for the sustained release of an active agent in the gastrointestinal tract, comprising:

• an internal layer, including a first side, an opposing second side, and an outer-facing peripheral side extending between respective edges of the first side and the second side,
• comprising an active agent, degradable hydrophilic polymer, degradable enteric polymer which is substantially insoluble at pH less than 5.5, and a plasticizer, the active agent, the degradable hydrophilic polymer and the degradable enteric polymer being uniformly distributed throughout said internal layer;
• and
• two outer membranes, each being larger in size than said internal layer, one of said outer membranes covering the first side of said internal layer and the other of said outer membranes covering the second side of said internal layer and contacting said peripheral side, each said outer membrane having a length greater than 20 mm in a planar orientation and each comprising at least one polymeric combination of a hydrophilic polymer, a polymer that is insoluble in gastric media, and at least one plasticizer, each said outer membrane being configured for swelling in the presence of gastric medium,
• wherein one of the materials comprised in said internal layer and one of the materials comprised in each said outer membrane are capable of being ultrasonically welded together,
• wherein said two outer membranes and said internal layer are arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach,
• wherein said two outer membranes permit passage of gastric fluid from the stomach to said internal layer and permit passage of gastric fluid and the active agent from said internal layer through said two outer membranes to the stomach, and
• wherein said internal layer and said two outer membranes secured thereto provide mechanical force sufficient to unfold from the accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric fluid.

A gastroretentive drug delivery system for the sustained release of an active agent in the gastrointestinal tract, comprising:

• an internal layer, including a first side, an opposing second side, and an outer-facing peripheral side extending between respective edges of the first side and the second side, comprising an active agent, a degradable hydrophilic polymer which is not instantly soluble in gastric fluid, a degradable enteric polymer which is substantially insoluble at pH less than 5.5, and a plasticizer,
• the active agent, the degradable hydrophilic polymer, and the degradable enteric polymer being uniformly distributed throughout said internal layer;
• and
• first and second outer membranes, each having a width and length larger in size that those of said internal layer, the first outer membrane covering and being secured, by ultrasonic welding, to the first side of said internal layer and the second outer membrane covering and being secured, by ultrasonic welding, to the second side of said internal layer and contacting said peripheral side, said outer membranes each including at least one polymeric combination of a hydratable swelling polymer, an enteric polymer, and at least one plasticizer, the membrane swelling in the presence of gastric fluid, the outer membranes permitting passage of gastric fluid from the stomach to said internal layer and permitting passage of gastric fluid and the active agent from said internal layer through said outer membranes to the stomach,
• one of the materials in said internal layer and one of the materials in each of said outer membranes being capable of being ultrasonically welded together,
• wherein said internal layer and said first and second outer membranes have a length greater than 20 mm in a planar orientation, said internal layer and said outer membranes attached thereto being arranged in an accordion folded configuration of a size permitting placement within a capsule for oral intake, which capsule is dissolvable within the stomach,
• wherein said internal layer and said outer membranes secured thereto are capable of providing mechanical force sufficient to unfold from the accordion folded configuration to an unfolded configuration having a length of at least 20 mm within 30 minutes of being exposed to gastric fluid, and
• wherein the ultrasonic welds having sufficient mechanical strength to remain intact upon being exposed to gastric medium.