Minimization of drug oxidation in drug irradiated excipients formulations

Abstract

This invention relates to compositions and methods for preventing oxidation of beneficial agents that comprise at least one beneficial agent and an excipient, wherein the excipient has been irradiated and annealed.

1 . A formulation for preventing oxidation of a beneficial agent comprising: at least one beneficial agent; and 
 an excipient, wherein the excipient has been irradiated and annealed.    
     
     
         2 . The formulation of  claim 1  wherein the excipient comprises stearic acid.  
     
     
         3 . The formulation of  claim 1  wherein the excipient comprises a fatty acid.  
     
     
         4 . The formulation of  claim 1  wherein the excipient is palmitic acid, stearic acid, or C 20-22  fatty acids.  
     
     
         5 . The formulation of  claim 1  wherein the excipient comprises a natural polymer.  
     
     
         6 . The formulation of  claim 5  wherein the excipient comprises polysaccharides.  
     
     
         7 . The formulation of  claim 1  wherein the excipient comprises a synthetic polymer.  
     
     
         8 . The formulation of  claim 7  wherein the excipient comprises a polymer selected from the group of polyethylene glycol, polyvinylpyrrolidone, and polyvinyl alcohol.  
     
     
         9 . The formulation of  claim 1  wherein the beneficial agent is selected from the group consisting of a protein, a peptide, a lipid, a DNA sequence, an RNA sequence, a drug, and combinations thereof.  
     
     
         10 . The formulation of  claim 9  wherein the beneficial agent is a protein selected from the group consisting of human growth hormone, lysozyme, interferon alpha-2a, interferon alpha-2b, EPO, methionine-human growth hormone, des-phenylalanine human growth hormone, consensus interferon, albumin, omega-interferon, immunoglobulins, interleukines, G-CSF, GM-CG, TNFs hot shock proteins, and combinations thereof.  
     
     
         11 . The formulation of  claim 9  wherein the beneficial agent is a peptide having at least one amino acid selected from the group consisting of cystein, methionine, tyrosine, tryptophan, phenylalanine, valine, leucine, histidine, glutamic acid, proline, threonine, arginine, and lysine.  
     
     
         12 . The formulation of  claim 9  wherein the beneficial agent is a drug selected from the group consisting of epinephrine, theophyllin, risperidone, captopril, chlorpromazine, ergotamine, hydrocortisone, morphine, promethazine, and thiamine.  
     
     
         13 . The formulation of  claim 1  further comprising a delivery platform.  
     
     
         14 . The formulation of  claim 13  wherein the delivery platform comprises a gel vehicle formulation comprising a bioerodible, biocompatible polymer and a solvent in an amount effective to plasticize the polymer and foini a gel therewith.  
     
     
         15 . The formulation of  claim 14  wherein the polymer is selected from the group consisting of: polylactides, polyglycolides, polyanhydrides, polyamines, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyphosphoesters, polyoxaesters, polyorthocarbonates, polyphosphazenes, succinates, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, polyphosphoesters, chitin, chitosan, gluronic acid, and copolymers, terpolymers and mixtures thereof.  
     
     
         16 . The formulation of  claim 13  wherein the delivery platform comprises a polymeric matrix which encapsulates a mixture of excipient and beneficial agent.  
     
     
         17 . The formulation of  claim 16  wherein the matrix comprises a polymer selected from the group consisting of: polylactides, polyglycolides, polyanhydrides, polyamines, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyphosphoesters, polyoxaesters, polyorthocarbonates, polyphosphazenes, succinates, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, polyphosphoesters, chitin, chitosan, gluronic acid, and copolymers, terpolymers and mixtures thereof.