Compositions and methods involving polymer, solvent, and high viscosity liquid carrier material

Abstract

Compositions may include a pharmaceutical active agent, a high viscosity liquid carrier material (HVLCM), a lactic acid-based polymer, and an organic solvent. Related compositions and methods are also disclosed.

1 .- 47 . (canceled) 
     
     
         48 . A composition comprising:
 5 wt % to 20 wt %, based on total weight of the composition, of particles comprising pharmaceutical active agent that is risperidone or pharmaceutically acceptable salt thereof, the particles having a median particle size, as measured by laser diffraction, ranging from 0.5 micrometer to 7 micrometers;   30 wt % to 60 wt %, based on total weight of the composition, of a non-polymeric, non-water soluble high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37° C. that does not crystallize neat at 25° C. and 1 atmosphere, wherein the HVLCM is sucrose acetate isobutyrate;   5 wt % to 30 wt %, based on total weight of the composition, of a lactic acid based-polymer that is poly(lactic acid)(glycolic acid) comprising an alkoxy end group, the poly(lactic acid)(glycolic acid) having a lactic acid to glycolic acid molar ratio ranging from 95:5 to 60:40, the poly(lactic acid)(glycolic acid) having a weight average molecular weight ranging from 4000 Daltons to 15,000 Daltons; and   10 wt % to 40 wt %, based on total weight of the composition, of a solvent that is at least one member selected from N-methyl-pyrrolidone, propylene carbonate, and dimethylsulfoxide.   
     
     
         49 . The composition of  claim 48 , which is a gamma-irradiated composition. 
     
     
         50 .- 51 . (canceled) 
     
     
         52 . The composition of  claim 48 , wherein a weight ratio of the HVLCM to the lactic acid-based polymer to the solvent ranges from 1:0.25-0.5:0.4-0.8. 
     
     
         53 .- 56 . (canceled) 
     
     
         57 . The composition of  claim 48 , wherein the composition has a viscosity ranging from 50 cP to 2000 cP. 
     
     
         58 .- 70 . (canceled) 
     
     
         71 . The composition of  claim 48 , wherein the alkoxy end group consists of 8 to 24 carbons. 
     
     
         72 . The composition of  claim 71 , wherein the alkoxy end group consists of 12 carbons. 
     
     
         73 . The composition of  claim 71 , wherein the lactic acid-based polymer is initiated with a fatty alcohol. 
     
     
         74 . (canceled) 
     
     
         75 . The composition of  claim 71 , wherein the lactic-acid based polymer is initiated with dodecanol. 
     
     
         76 .- 82 . (canceled) 
     
     
         83 . A needle-free injector comprising:
 a drug capsule, wherein the drug capsule is closed at one end by a piston;   a triggering mechanism; and   a self-contained energy source,   wherein the drug capsule contains a composition comprising:   a pharmaceutical active agent;   25 wt % to 80 wt %, based on total weight of the composition, of a non-polymeric, non-water soluble high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37° C. that does not crystallize neat at 25° C. and 1 atmosphere;   a lactic acid-based polymer comprising an alkoxy end group; and   an organic solvent.   
     
     
         84 .- 96 . (canceled) 
     
     
         97 . The needle-free injector of  claim 83 , wherein the drug capsule comprises at least one injection orifice. 
     
     
         98 . The needle-free injector of  claim 97 , wherein the at least one injection orifice is closed during storage by a sealing element. 
     
     
         99 .- 106 . (canceled) 
     
     
         107 . The needle-free injector of  claim 83 , wherein the self-contained energy source comprises at least one member selected from:
 a compressed mechanical spring,   a compressed gas,   a pyrotechnic charge, and   a battery.   
     
     
         108 .- 114 . (canceled) 
     
     
         115 . A method of administering a pharmaceutical active agent comprising:
 subcutaneously administering an effective amount of a composition to a patient in need thereof, wherein the composition comprises:   particles comprising pharmaceutical active agent, the particles having a median particle size, as measured by laser diffraction, ranging from 0.5 micrometers to 10 micrometers;   25 wt % to 80 wt %, based on total weight of the composition, of a non-polymeric, non-water soluble high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37° C. that does not crystallize neat at 25° C. and 1 atmosphere;   a lactic acid-based polymer; and   an organic solvent.   
     
     
         116 .- 117 . (canceled) 
     
     
         118 . The method of  claim 115 , wherein the pharmaceutical active agent and any metabolites thereof have a plasma level in the patient of at least 5 ng/mL at 28 days after administration. 
     
     
         119 . The method of  claim 115 , wherein the median Cmax of the pharmaceutical active agent ranges from 50 ng/mL to 300 ng/mL. 
     
     
         120 .- 121 . (canceled) 
     
     
         122 . The method of  claim 115 , wherein the median Cmax to Cmin ratio of the pharmaceutical active agent, as measured over 14 days after administration, ranges from 2 to 40. 
     
     
         123 .- 124 . (canceled) 
     
     
         125 . The method of  claim 115 , wherein an amount of pharmaceutical active agent delivered into plasma at 24 hours of subcutaneous administration divided by an amount of pharmaceutical active agent delivered at 4 weeks of administration ranges from 0.05 to 0.15. 
     
     
         126 . (canceled) 
     
     
         127 . The method of  claim 115 , wherein the pharmaceutical active agent is an anti-schizophrenia agent and the method is a method of treating at least one of schizophrenia and bipolar disorder. 
     
     
         128 . The method of  claim 127 , wherein the anti-schizophrenia agent comprises risperidone or pharmaceutically acceptable salt thereof. 
     
     
         129 .- 141 . (canceled)