Non-Aqueous Single Phase Vehicles and Formulations Utilizing Such Vehicles

Abstract

The present invention is related to materials and methods for forming polymeric delivery vehicles that reduces risk of oxidative degradation of a carried drug and the resulting compositions.

1 - 41 . (canceled) 
     
     
         42 . A method comprising:
 combining methionine with the biocompatible polymer to obtain a polymer preparation;   combining the polymer preparation with a solvent to form a drug delivery vehicle solution; and   combining the drug delivery vehicle solution with a drug to form a drug delivery formulation comprising the drug suspended in the drug delivery vehicle solution and wherein the drug delivery formulation is nonaqueous.   
     
     
         43 . The method of  claim 42 , wherein about less than 35% of the drug in the drug delivery formulation is degraded by oxidation, deamidation, and hydrolysis after maintenance of the drug delivery formulation at 37° C. for a period of two months. 
     
     
         44 . The method of  claim 42 , wherein about less than 15% of the drug in the drug delivery formulation is degraded through aggregation after maintenance of the drug delivery formulation at 37° C. for a period of two months. 
     
     
         45 . The method of  claim 42 , wherein the drug comprises a particulate material. 
     
     
         46 . The method of  claim 42 , wherein the drug comprises medicines, vitamins, nutrients, or food supplements. 
     
     
         47 . The method of  claim 42 , wherein the drug comprises a peptide or protein. 
     
     
         48 . The method of  claim 42 , wherein the drug comprises at least one member selected from adrenocorticotropic hormone, angiotensin I, angiotensin II, atrial natriuretic peptide, bombesin, bradykinin, calcitonin, cerebellin, dynorphin, alpha endorphin, beta endorphin, endothelin, enkephalin, epidermal growth factor, fertirelin, follicular gonadotropin releasing peptide, galanin, glucagon, glucagon-like-peptide-1 (GLP-1), gonadorelin, gonadotropin, goserelin, growth hormone releasing peptide, histrelin, human growth hormone, insulin, interferons, leuprolide, luteinizing hormone-releasing hormone (LHRH), motilin, nafarerlin, neurotensin, oxytocin, relaxin, somatostatin, substance P, tumor necrosis factor, triptorelin, vasopressin, growth hormone, nerve growth factor, blood clotting factors, ribozymes, and antisense oligonucleotides. 
     
     
         49 . The method of  claim 42 , wherein the biocompatible polymer comprises at least one member selected from polyester, pyrrolidone, polyethylene glycol, methyl cellulose, ester of unsaturated alcohol, ether of unsaturated alcohol, and polyoxyethylene/polyoxypropylene block copolymer. 
     
     
         50 . The method of  claim 42 , wherein the solvent comprises at least one member selected from glycofurol, tetraglycol, n-methylpyrrolidone, glycerol formal, glycerine, and propylene glycol. 
     
     
         51 . The method of  claim 42 , wherein the drug formulation exhibits peroxide levels below 5 ppm. 
     
     
         52 . The method of  claim 42 , wherein the weight ratio of methionine to polymer following the addition of the methionine to the biocompatible polymer preparation is from 1 to 50 to 1 to 2. 
     
     
         53 . The method of  claim 42 , wherein the polymer is water soluble. 
     
     
         54 . The method of  claim 42 , wherein the biocompatible polymer comprises polyvinylpyrrolidone, polyethylene glycol, or methyl cellulose. 
     
     
         55 . The method of  claim 42 , wherein the biocompatible polymer comprises polyvinylpyrrolidone. 
     
     
         56 . The method of  claim 42 , wherein the methionine is L-methionine. 
     
     
         57 . The method of  claim 42 , wherein the drug delivery vehicle solution has a viscosity ranging from about 1000 poise to about 10,000,000 poise. 
     
     
         58 . The method of  claim 42 , wherein the polymer ranges from about 40 wt % to about 80 wt %, based on the drug delivery vehicle solution. 
     
     
         59 . The method of  claim 42 , wherein the solvent ranges from about 20 wt % to about 60 wt %, based on the drug delivery vehicle solution. 
     
     
         60 . The method of  claim 42 , wherein the drug is stable in the drug delivery formulation at 37° C. for at least two months. 
     
     
         61 . The method of  claim 42 , further comprising administering the drug delivery formulation to a patient.