Methods of manufacturing viscous liquid pharmaceutical formulations

Abstract

A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

What is claimed is: 
     
         1 . A liquid composition in an osmotic drug delivery system comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent. 
     
     
         2 . The composition of  claim 1 , wherein the amphiphilic molecule is selected from lipid, surfactant, amphiphilic block polymer, or amphiphilic proteins or peptides. 
     
     
         3 . The composition of  claim 1 , wherein said pharmaceutically active agent is suspended in a particle within said liquid composition. 
     
     
         4 . The composition of  claim 1 , further comprising an anti-oxidant lipid compound selected from vitamin E, α-tocopherol, or ascorbic acid. 
     
     
         5 . The composition of  claim 1  wherein the pharmaceutically active agent is selected from a protein, peptide, small molecule drug, lipid drug or nucleic acid drug, DNA drug, RNA drug, antisense drug, ribozyme drug, DNAzyme drug. 
     
     
         6 . The composition of  claim 1  wherein an amphiphilic molecule weight percent is from about 1 to about 100 weight percent. 
     
     
         7 . The composition of  claim 1  wherein the non-aqueous liquid solvent weight percent is from about 0 to about 99 weight percent. 
     
     
         8 . The composition of  claim 1 , wherein viscosity of the composition is from about 1 to about 100,000 poise. 
     
     
         9 . The composition of  claim 1 , wherein the pharmaceutically active agent is selected from biologically or pharmacologically active substance. 
     
     
         10 . A dosage form comprising a dosage form selected from the group consisting of:
 (i) a drug dosage form for osmotic drug delivery comprising:
 a capsule including a first chamber containing a viscous liquid pharmaceutical composition and a second chamber containing an osmotic agent, said first chamber having an opening through which the pharmaceutical composition can be delivered from the first chamber to a location external of the first chamber; 
 a movable separating member positioned in the capsule between the first chamber and the second chamber; 
 a wall of the second chamber including a fluid permeable portion allowing fluid to pass from a surrounding environment into the second chamber; and 
 an incompressible fluid additive located within the second chamber and substantially surrounding the osmotic agent; and 
   (ii) a dosage form
 dosage form comprising: 
 a first wall that maintains its physical and chemical integrity during the life of the dosage form and is substantially impermeable to a pharmaceutical suspension; 
 a second wall that is partially permeable to an exterior fluid; 
 a compartment defined by the first wall and the second wall; 
 a pharmaceutical suspension that is positioned within the compartment and comprises an amphiphilic molecule, a non-aqueous solvent, a performance modifier, and a pharmaceutically active agent; and 
 an exit port in the wall in communication with the compartment. 
   
     
     
         11 . The dosage form of  claim 10 , wherein the viscous liquid pharmaceutical composition comprises an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent. 
     
     
         12 . The dosage form of  claim 10 , wherein the osmotic agent is in a tabular form and the fluid additive surrounds the tabular osmotic agent. 
     
     
         13 . The dosage form of  claim 10 , wherein the separating member is a slidable piston. 
     
     
         14 . The dosage form of  claim 10 , wherein the fluid permeable portion is a membrane. 
     
     
         15 . A suspending vehicle in a pump-driven dosage form comprising an amphiphilic molecule, a non-aqueous solvent, and a performance modifier. 
     
     
         16 . The suspending vehicle of  claim 15  which is substantially non-aqueous. 
     
     
         17 . The suspending vehicle of  claim 15  wherein the amphiphilic molecule comprises a lipid. 
     
     
         18 . A method comprising:
 identifying an amphiphilic molecule;   identifying a non-aqueous solvent;   identifying a performance modifier;   mixing the amphiphilic molecule, the non-aqueous solvent, and the performance modifier to create a suspending vehicle.   
     
     
         19 . The method of  claim 18  further comprising adding a pharmaceutically active agent to the suspending vehicle to create a pharmaceutical suspension. 
     
     
         20 . A method comprising administering the dosage form of  claim 10  to a mammal. 
     
     
         21 . A kit comprising a dosage form of  claim 10  and instructions for administering the dosage form.