Short duration depot formulations

Abstract

Methods and compositions for systemically or locally administering by implantation a beneficial agent to a subject are described, and include, for example, depot gel compositions that can be injected into a desired location and which can provide controlled release of a beneficial agent over a short duration of time. The compositions include a low molecular weight biocompatible polymer, a biocompatible solvent having low water miscibility that forms a viscous gel with the polymer and limits water uptake by the implant, and a beneficial agent.

1 . An injectable depot composition for sustained delivery of a beneficial agent to a subject comprising: 
 (a) a low molecular weight bioerodible, biocompatible polymer;    (b) a solvent selected from the group consisting of aromatic alcohols, esters of aromatic acids, aromatic ketones, and mixtures thereof, said solvent having miscibility in water of less than or equal to 7% at 25° C., and present in an amount effective to plasticize the polymer and form a gel therewith; and    (c) a beneficial agent;    wherein the beneficial agent is delivered in a controlled manner over a duration equal to or less than two weeks.    
   
   
       2 . The injectable depot composition of  claim 1  wherein the beneficial agent is delivered systemically.  
   
   
       3 . The injectable depot composition of  claim 1  wherein the beneficial agent is delivered locally.  
   
   
       4 . The injectable depot composition of  claim 1  wherein the low molecular weight polymer has a molecular weight ranging from about 3000 to about 10,000.  
   
   
       5 . The injectable depot composition of  claim 1 , wherein the polymer is selected from the group consisting of polylactides, polyglycolides, polyanhydrides, polyamines, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyphosphoesters, polyorthocarbonates, polyphosphazenes, succinates, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, hylauronic acid and copolymers, terpolymers and mixtures thereof.  
   
   
       6 . The injectable depot composition of  claim 5 , wherein the polymer is a lactic acid-based polymer.  
   
   
       7 . The injectable depot composition of  claim 1 , wherein the polymer represents about 10 wt. % to about 85 wt. % of the composition.  
   
   
       8 . The injectable depot composition of  claim 1 , wherein the aromatic alcohol is benzyl alcohol and the ester of an aromatic acid is a lower alkyl ester or an aralkyl ester of benzoic acid.  
   
   
       9 . The injectable depot composition of  claim 1  wherein the beneficial agent is selected from a drug, proteins, enzymes, hormones, polynucleotides, nucleoproteins, polysaccharides, glycoproteins, lipoproteins, polypeptides, steroids, analgesics, local anesthetics, antibiotic agents, chemotherapeutic agents, immunosuppressive agents, anti-inflammatory agents, antiproliferative agents, antimitotic agents, angiogenic agents, antipsychotic agents, central nervous system (CNS) agents, anticoagulants, fibrinolytic agents, growth factors, antibodies, ocular drugs, and metabolites, analogs, derivatives, and fragments thereof.  
   
   
       10 . The injectable depot composition of  claim 9  wherein the beneficial agent is in the form of particles wherein the particle further comprises a component selected from the group consisting of a stabilizing agent, bulking agent, chelating agent and a buffering agent.  
   
   
       11 . A method of administering a beneficial agent to a subject in a controlled manner over a duration equal to or less than two weeks, comprising administering an injectable depot composition comprising: 
 (a) a low molecular weight bioerodible, biocompatible polymer;    (b) a solvent selected from the group consisting of aromatic alcohols, esters of aromatic acids, aromatic ketones, and mixtures thereof, said solvent having miscibility in water of less than or equal to 7% at 25° C., and present in an amount effective to plasticize the polymer and form a gel therewith; and    (c) a beneficial agent.    
   
   
       12 . The method of  claim 11 , wherein wherein the beneficial agent is delivered systemically in a controlled manner over a duration equal to or less than two weeks.  
   
   
       13 . The method of  claim 11 , wherein the system releases within 24 hours after implantation less than or equal to 20% by weight of the amount of beneficial agent to be delivered over the duration of the delivery period, wherein the delivery period is 2 weeks.  
   
   
       14 . The method of  claim 11 , wherein wherein the beneficial agent is delivered systemically in a controlled manner over a duration equal to or less than two weeks.  
   
   
       15 . The method of  claim 11  wherein the low molecular weight polymer has a molecular weight ranging from about 3000 to about 10,000.  
   
   
       16 . The method of  claim 11 , wherein the polymer is selected from the group consisting of polylactides, polyglycolides, polyanhydrides, polyamines, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyphosphoesters, polyorthocarbonates, polyphosphazenes, succinates, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, hylauronic acid and copolymers, terpolymers and mixtures thereof.  
   
   
       17 . The method of  claim 16 , wherein the polymer is a lactic acid-based polymer.  
   
   
       18 . The method of  claim 11 , wherein the polymer represents about 10 wt. % to about 85 wt. % of the composition.  
   
   
       19 . The method of  claim 11 , wherein the beneficial agent is selected from a drug, proteins, enzymes, hormones, polynucleotides, nucleoproteins, polysaccharides, glycoproteins, lipoproteins, polypeptides, steroids, analgesics, local anesthetics, antibiotic agents, chemotherapeutic agents, immunosuppressive agents, anti-inflammatory agents, antiproliferative agents, antimitotic agents, angiogenic agents, antipsychotic agents, central nervous system (CNS) agents, anticoagulants, fibrinolytic agents, growth factors, antibodies, ocular drugs, and metabolites, analogs, derivatives, and fragments thereof.  
   
   
       20 . The method of  claim 19  wherein the beneficial agent is in the form of particles wherein the particle further comprises a component selected from the group consisting of a stabilizing agent, bulking agent, chelating agent and a buffering agent.