US2018355071A1PendingUtilityA1

Methods and systems for polymer precipitation and generation of particles

74
Assignee: CERULEAN PHARMA INCPriority: Apr 18, 2012Filed: Aug 21, 2018Published: Dec 13, 2018
Est. expiryApr 18, 2032(~5.8 yrs left)· nominal 20-yr term from priority
C08B 37/0012
74
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Claims

Abstract

Processes for precipitating a polymer from a polymer-containing fluid are disclosed, which include providing a vessel housing a medium that provides one or more precipitation surfaces. A polymer-containing fluid, e.g., a polymer solution, dispersion or mixed solution/dispersion, and an anti-solvent can be introduced into the vessel so as to cause precipitation of at least a portion of the polymer on at least one of the precipitation surfaces. In some embodiments, the polymer contains one or more cyclic oligosaccharide moieties, such as one or more cyclodextrin moieties (e.g., α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin). The polymer can be any of a linear or branched polymer. The polymer can be any of polycation, a polyanion, or a non-ionic polymer. Also disclosed herein are precipitation surfaces with polymer precipitated thereon.

Claims

exact text as granted — not AI-modified
1 . A process for precipitating a polymer from a polymer-containing fluid, comprising:
 providing a vessel housing a medium, the medium providing one or more precipitation surfaces,   introducing a polymer-containing fluid and an anti-solvent into the vessel so as to cause precipitation of at least a portion of the polymer on at least one of said precipitation surfaces,   wherein the polymer contains one or more cyclic oligosaccharide moieties.   
     
     
         2 . The process of  claim 1  wherein the process further comprises extracting at least a portion of the polymer-containing fluid and the anti-solvent from the vessel and recirculating the mixture thorough the vessel and medium to induce further precipitation. 
     
     
         3 . The process of  claim 1 , wherein said medium is porous. 
     
     
         4 . The process of  claim 3 , wherein said porous medium comprises a mesh. 
     
     
         5 . The process of  claim 3 , wherein said porous medium comprises a plurality of insoluble supports providing said precipitation surfaces. 
     
     
         6 . The process of  claim 4 , wherein said mesh is formed at least partially of a metal. 
     
     
         7 . The process of  claim 6 , wherein said metal comprises any of stainless steel, gold and silver. 
     
     
         8 . The process of  claim 4 , wherein said mesh is formed at least partially of a polymeric material. 
     
     
         9 . The process of  claim 8 , wherein said polymeric material comprises polytetrafluoroethylene (PTFE). 
     
     
         10 . The process of  claim 5 , wherein said insoluble supports having said precipitation surfaces exhibit a size in a range of about 10 microns to about 1 millimeter. 
     
     
         11 . The process of  claim 5 , wherein said insoluble supports having said precipitation surfaces exhibit a size in a range of about 10 microns to about 200 microns. 
     
     
         12 . The process of  claim 5 , wherein said insoluble supports having said precipitation surfaces comprise a powder of diatomaceous earth. 
     
     
         13 . The process of  claim 1 , wherein said medium is inert to any of said anti-solvent, said polymer-containing fluid, and said polymer. 
     
     
         14 . The process of  claim 1 , wherein said polymer in said polymer-containing fluid has an average molecular weight between 50 kDa and 100 kDa. 
     
     
         15 . The process of  claim 14 , wherein said polymer has an average molecular weight in a range of about 70 kDa to about 80 kDa. 
     
     
         16 . The process of  claim 1 , further introducing at least a portion of said anti-solvent into said vessel prior to the introduction of the polymer-containing fluid into the vessel. 
     
     
         17 . The process of  claim 16 , further comprising agitating said anti-solvent present in the vessel and introducing said polymer-containing fluid into the agitated anti-solvent. 
     
     
         18 . The process of  claim 1 , further comprising causing a flow of the anti-solvent through said vessel. 
     
     
         19 . The process of  claim 18 , wherein the polymer-containing fluid is introduced into said flowing anti-solvent. 
     
     
         20 . The process of  claim 1 , wherein the polymer in said polymer-containing fluid is immiscible in said anti-solvent. 
     
     
         21 . The process of  claim 20 , wherein said polymer-containing fluid is at least partially miscible in said anti-solvent. 
     
     
         22 . The process of  claim 1 , wherein said polymer-containing fluid comprises any of a polymer solution, a polymer dispersion, and a mixed polymer solution/dispersion. 
     
     
         23 . The process of  claim 1 , wherein said polymer-containing fluid comprises a polymer solution, said polymer solution comprising a quantity of said polymer dissolved in a process solvent, wherein said process solvent is at least partially miscible with said anti-solvent. 
     
     
         24 . The process of  claim 1 , wherein the polymer in said polymer-containing fluid comprises a plurality of cyclodextrin moieties. 
     
     
         25 . The process of  claim 24 , wherein at least one of said cyclodextrin moieties comprises α-cyclodextrin. 
     
     
         26 . The process of  claim 24 , wherein at least one of said cyclodextrin moieties comprises β-cyclodextrin. 
     
     
         27 . The process of  claim 24 , wherein at least one of said cyclodextrin moieties comprises γ-cyclodextrin. 
     
     
         28 . The process of  claim 24 , wherein said cyclodextrin moieties form any of a linear and branched polymer. 
     
     
         29 . The process of  claim 1 , wherein the polymer in said polymer-containing fluid comprises a therapeutic agent covalently attached thereto. 
     
     
         30 . The process of  claim 29 , wherein said therapeutic agent is any of anti-cancer agent, an anti-inflammatory agent, or a cardiovascular active agent. 
     
     
         31 . The process of  claim 29 , wherein said therapeutic agent is any of a taxane, an epothilone, a boronic acid proteasome inhibitor, and an anti-biotic. 
     
     
         32 . The process of  claim 29 , wherein said therapeutic agent is an anti-metabolite. 
     
     
         33 . The process of  claim 1 , wherein said polymer comprises a bioactive agent. 
     
     
         34 . The process of  claim 33 , wherein said bioactive agent comprises any of a diagnostic agent and an adjuvant. 
     
     
         35 . The process of  claim 1 , wherein said polymer-containing fluid comprises acetone, ether, alcohol, tetrahydrofuran, 2-pyrrolidone, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, methyl acetate, ethyl formate, methyl ethyl ketone, methyl isobutyl ketone, methyl propyl ketone, isopropyl ketone, isopropyl acetate, acetonitrile, dimethyl sulfoxide, or a combination thereof. 
     
     
         36 . The process of  claim 1 , wherein said anti-solvent comprises any of an organic solvent or a mixture of two or more organic solvents. 
     
     
         37 . The process of  claim 1 , wherein said anti-solvent comprises methanol, ethanol, acetone, n-propanol, isopropanol, n-butanol, ethyl ether, methyl isobutyl ketone or ethyl acetate or a combination thereof. 
     
     
         38 . The process of  claim 1 , further comprising collecting at least a portion of said medium subsequent to precipitation of at least some of the polymer on said precipitation surfaces. 
     
     
         39 . The process of  claim 1 , further comprising drying said collected portion of the medium. 
     
     
         40 . The process of  claim 1 , further comprising terminating the introduction of the polymer-containing fluid into the vessel after precipitation of some of the polymer on the precipitation surfaces and washing said precipitation surfaces with the same or a different anti-solvent. 
     
     
         41 . The process of  claim 40 , wherein the washing step comprises introducing the same or a different anti-solvent into the vessel so as to be in contact with said polymer-coated surfaces. 
     
     
         42 . The process of  claim 1 , further comprising placing said polymer-coated precipitation surfaces in contact with a stripping liquid to strip at least a portion of said precipitated polymer from the precipitation surfaces so as to form a plurality of polymeric particles (e.g., nanoparticles) in said stripping liquid. 
     
     
         43 . The process of  claim 42 , wherein said stripping liquid comprises a polar liquid. 
     
     
         44 . The process of  claim 42 , wherein said stripping liquid comprises water and an optional salt, wetting agent, or pH adjuster. 
     
     
         45 . The process  claim 42 , wherein said polymeric nanoparticles exhibit an average particle size less than about 200 nm. 
     
     
         46 . The process of  claim 45 , wherein said polymeric nanoparticles exhibit an average particle size less than about 100 nm. 
     
     
         47 . The process of  claim 45 , wherein said polymeric nanoparticles exhibit an average particle size less than about 50 nm. 
     
     
         48 . The process of  claim 45 , wherein said polymeric nanoparticles exhibit an average particle size in a range of about 5 nm to about 200 nm. 
     
     
         49 . The process of  claim 42 , wherein said polymeric particles (e.g., nanoparticles) exhibit a polydispersity index in a range of about 0.1 to about 0.5. 
     
     
         50 . The process of  claim 42 , further comprising filtering said stripping liquid containing the polymeric particles (e.g., nanoparticles) to obtain a retentate containing said polymeric particles (e.g., nanoparticles). 
     
     
         51 . The process of  claim 50 , wherein said filtering step comprises employing tangential flow filtration. 
     
     
         52 . The process of  claim 50 , further comprising collecting at least a portion of said polymer-coated insoluble supports and drying said collected insoluble supports. 
     
     
         53 . The process of  claim 52 , wherein the step of collecting the polymer-coated insoluble supports comprises separating said polymer-coated insoluble supports from at least a portion of a liquid present in the housing subsequent to precipitation of the polymer on the precipitation surfaces. 
     
     
         54 . The process of  claim 53 , wherein said separating step comprises utilizing any of centrifugation and filtration. 
     
     
         55 . The process of  claim 53 , wherein said drying step comprises utilizing a vacuum to remove at least a portion of residual liquid present in said polymer-coated insoluble supports. 
     
     
         56 . The process of  claim 55 , wherein said drying step comprises utilizing a gaseous purge to remove at least a portion of residual liquid present in said polymer-coated insoluble supports. 
     
     
         57 . A process for precipitating a polymer from a polymer-containing fluid, comprising:
 establishing a flow of an anti-solvent through a porous medium, said medium providing one or more precipitation surfaces, and   introducing a polymer-containing fluid into the flowing anti-solvent so as to cause precipitation of at least a portion of the polymer on said one or more precipitation surfaces,   wherein said polymer contains one or more cyclic oligosaccharide moieties.   
     
     
         58 . The process of  claim 57 , further comprising disposing said porous medium within a vessel and establishing the anti-solvent flow through said vessel. 
     
     
         59 . The process of  claim 57 , wherein said porous medium comprises a mesh. 
     
     
         60 . The process of  claim 59 , wherein said mesh is formed at least partially of a metal. 
     
     
         61 . The process of  claim 60 , wherein said metal comprises any of stainless steel, gold and silver. 
     
     
         62 . The process of  claim 59 , wherein said mesh is formed at least partially of a ceramic material. 
     
     
         63 . The process of  claim 59 , wherein said mesh is formed at least partially of a polymeric material. 
     
     
         64 . The process of  claim 63 , wherein said polymeric material comprises polytetrafluoroethylene (PTFE). 
     
     
         65 . The process of  claim 57 , wherein said porous medium comprises a plurality of insoluble supports providing said precipitation surfaces. 
     
     
         66 . The process of  claim 65 , wherein said insoluble supports providing said precipitation surfaces have a size in a range of about 10 microns to about 1 millimeter. 
     
     
         67 . The process of  claim 65 , wherein said insoluble supports providing the precipitation surfaces have a size in a range of about 10 microns to about 200 microns. 
     
     
         68 . The process of  claim 65 , wherein said insoluble supports providing the precipitation surfaces comprise a powder of diatomaceous earth. 
     
     
         69 . The process of  claim 57 , wherein said polymer comprises a plurality of cyclodextrin moieties. 
     
     
         70 . The process of  claim 57 , further comprising continuing the flow of the anti-solvent through the porous medium for a time period after the introduction of the polymer-containing fluid into the flowing anti-solvent is terminated. 
     
     
         71 . The process of  claim 57 , further comprising placing said polymer-coated surfaces in contact with a stripping liquid to strip at least a portion of the precipitated polymer from said surfaces so as to form a plurality of polymeric particles (e.g., nanoparticles) in said stripping liquid. 
     
     
         72 . The process of  claim 71 , wherein the step of placing the polymer-coated surfaces in contact with a stripping liquid further comprises terminating the flow of the anti-solvent and the polymer-containing fluid through the porous medium after precipitation of at least a portion of the polymer on said one or more surfaces and establishing a flow of said stripping liquid through the porous medium so as to cause removal of at least a portion of said precipitated polymer from said one or more surfaces so as to form a plurality of polymeric particles (e.g., nanoparticles) in said stripping liquid. 
     
     
         73 . The process of  claim 72 , wherein said polymeric nanoparticles have an average size less than about 200 nm. 
     
     
         74 . The process of  claim 73 , wherein said polymeric nanoparticles have an average size less than about 100 nm. 
     
     
         75 . The process of  claim 74 , wherein said polymeric nanoparticles have an average size less than about 50 nm. 
     
     
         76 . The process of  claim 73 , wherein said polymeric nanoparticles have an average size in a range of about 5 nm to about 200 nm. 
     
     
         77 . The process of  claim 71 , wherein said polymeric particles exhibit a polydispersity index in a range of about 0.1 to about 0.5. 
     
     
         78 . The process of  claim 57 , wherein said polymer comprises a therapeutic agent covalently attached thereto. 
     
     
         79 . The process of  claim 78 , wherein said therapeutic agent is any of anti-cancer agent, an anti-inflammatory agent, or a cardiovascular active agent. 
     
     
         80 . The process of  claim 78 , wherein said therapeutic agent is an anti-metabolite. 
     
     
         81 . The process of  claim 57 , wherein said polymer comprises a bioactive agent. 
     
     
         82 . The process of  claim 81 , wherein said bioactive agent comprises any of a diagnostic agent and an adjuvant. 
     
     
         83 . The process of  claim 57 , wherein said polymer-containing fluid comprises acetone, ether, alcohol, tetrahydrofuran, 2-pyrrolidone, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, methyl acetate, ethyl formate, methyl ethyl ketone, methyl isobutyl ketone, methyl propyl ketone, isopropyl ketone, isopropyl acetate, acetonitrile, dimethyl sulfoxide, or a combination thereof. 
     
     
         84 . The process of  claim 83 , wherein said polymer-containing fluid comprises dimethylformamide or dimethyl sulfoxide 
     
     
         85 . A process for precipitating a polymer from a polymer-containing fluid, comprising:
 providing a vessel containing an anti-solvent and a plurality of insoluble supports in contact with said anti-solvent, said insoluble supports having a plurality of precipitation surfaces, and   introducing a polymer-containing fluid into said anti-solvent so as to cause precipitation of at least a portion of the polymer on said precipitation surfaces,   wherein the polymer contains one or more cyclic oligosaccharide moieties.   
     
     
         86 . The process of  claim 85 , wherein said insoluble supports having the precipitation surfaces exhibit a size in a range of about 10 microns to about 1 millimeter. 
     
     
         87 . The process of  claim 86 , wherein said insoluble supports having the precipitation surfaces exhibit a size in range of about 10 microns to about 200 microns. 
     
     
         88 . The process of  claim 85 , wherein said insoluble supports having the precipitation surfaces comprise a powder of diatomaceous earth. 
     
     
         89 . The process of  claim 85 , further comprising agitating said anti-solvent. 
     
     
         90 . The process of  claim 89 , further comprising introducing said polymer-containing fluid into said agitated anti-solvent. 
     
     
         91 . The process of  claim 85 , further comprising collecting at least a portion of the insoluble supports subsequent to precipitation of said polymer on the precipitation surfaces thereof. 
     
     
         92 . The process of  claim 91 , further comprising drying said collected insoluble supports. 
     
     
         93 . The process of  claim 85 , wherein said polymer has an average molecular weight of about 70 kDa to about 80 kDa. 
     
     
         94 . The process of  claim 85 , wherein said polymer-containing fluid comprises any of a polymer solution, a polymer dispersion, and a mixed polymer solution/dispersion. 
     
     
         95 . The process of  claim 85 , wherein said polymer-containing fluid comprises a polymer solution, said polymer solution comprising a quantity of said polymer dissolved in a process solvent, wherein said process solvent is at least partially miscible with said anti-solvent. 
     
     
         96 . The process of  claim 85 , wherein said polymer comprises a plurality of cyclodextrin moieties. 
     
     
         97 . The process of  claim 96 , wherein at least one of said cyclodextrin moieties comprises α-cyclodextrin. 
     
     
         98 . The process of  claim 96 , wherein at least one of said cyclodextrin moieties comprises β-cyclodextrin. 
     
     
         99 . The process of  claim 96 , wherein at least one of said cyclodextrin moieties comprises γ-cyclodextrin. 
     
     
         100 . The process of  claim 85 , wherein said polymer comprises a therapeutic agent covalently attached thereto. 
     
     
         101 . The process of  claim 100 , wherein said therapeutic agent is any of anti-cancer agent, an anti-inflammatory agent, or a cardiovascular active agent. 
     
     
         102 . The process of  claim 100 , wherein said therapeutic agent is any of a taxane, an epothilone, a boronic acid proteasome inhibitor, and an anti-biotic. 
     
     
         103 . A system for precipitating a polymer from a polymer-containing fluid, comprising:
 a vessel for containing an anti-solvent, said vessel having at least one input port and an output port,   a medium housed in said vessel, said medium providing one or more precipitation surfaces,   a pump in communication with the vessel and configured to cause a flow of the anti-solvent through the vessel so that said precipitation surfaces are in at least partial contact with said flowing anti-solvent,   wherein said input port is configured to allow introduction of a polymer-containing fluid into said flowing anti-solvent so as to cause precipitation of at least a portion of the polymer on said one or more precipitation surfaces.   
     
     
         104 . The system of  claim 103 , further comprising a reservoir in fluid communication with said vessel for storing a quantity of said polymer-containing fluid, wherein said polymer comprises one or more cyclic oligosaccharide moieties. 
     
     
         105 . The system of  claim 103 , further comprising a fluid passage extending between said output port and said input port. 
     
     
         106 . The system of  claim 105 , wherein said pump is in communication with said fluid passage for establishing a liquid recirculation loop through said vessel. 
     
     
         107 . The system of  claim 106 , further comprising a recovery port in communication with said fluid passage to drain any of the anti-solvent and the polymer-containing fluid from said recirculation loop. 
     
     
         108 . The system of  claim 103 , further comprising a reservoir for storing the anti-solvent, said reservoir being in fluid communication with said vessel. 
     
     
         109 . The system of  claim 103 , wherein said medium is porous. 
     
     
         110 . The system of  claim 109 , wherein said porous medium comprises a mesh. 
     
     
         111 . The system of  claim 111 , wherein said mesh is formed at least partially of a metal. 
     
     
         112 . The system of  claim 111 , wherein said metal comprises any of stainless steel, gold and silver. 
     
     
         113 . The system of  claim 111 , wherein said mesh is formed at least partially of a polymeric material. 
     
     
         114 . The system of  claim 113 , wherein said polymeric material comprises polytetrafluoroethylene (PTFE). 
     
     
         115 . The system of  claim 110 , wherein said mesh is formed at least partially of a ceramic. 
     
     
         116 . The system of  claim 109 , wherein said porous medium comprises a plurality of insoluble supports providing said precipitation surfaces. 
     
     
         117 . The system of  claim 116 , wherein said insoluble supports comprise a powder of diatomaceous earth. 
     
     
         118 . The system of  claim 103 , wherein said vessel contains a quantity of said anti-solvent. 
     
     
         119 . A process for generating polymeric particles, comprising
 providing a vessel housing a medium, the medium providing one or more precipitation surfaces,   introducing a polymer-containing fluid and an anti-solvent into the vessel so as to cause precipitation of at least a portion of the polymer on at least one of said precipitation surfaces, and   placing the precipitated polymer in contact with a stripping liquid to remove at least a portion of said precipitated polymer from said at least one precipitation surface so as to form a plurality of polymeric particles,   wherein the polymer contains one or more cyclic oligosaccharide moieties.   
     
     
         120 . The process of  claim 119 , further comprising causing a recirculating flow of the anti-solvent through the vessel and introducing the polymer-containing fluid into said flowing anti-solvent. 
     
     
         121 . The process of  claim 119 , wherein said medium is porous. 
     
     
         122 . The process of  claim 121 , wherein said porous medium comprises a mesh. 
     
     
         123 . The process of  claim 121 , wherein said porous medium comprises a plurality of insoluble supports providing said precipitation surfaces. 
     
     
         124 . The process of  claim 122 , wherein said mesh is formed at least partially of a metal. 
     
     
         125 . The process of  claim 124 , wherein said metal comprises any of stainless steel, gold and silver. 
     
     
         126 . The process of  claim 122 , wherein said mesh is formed at least partially of a polymeric material. 
     
     
         127 . The process of  claim 126 , wherein said polymeric material comprises polytetrafluoroethylene (PTFE). 
     
     
         128 . The process of  claim 123 , wherein said insoluble supports having said precipitation surfaces exhibit a size in a range of about 10 microns to about 1 millimeter. 
     
     
         129 . The process of  claim 128 , wherein said insoluble supports having said precipitation surfaces exhibit a size in a range of about 10 microns to about 200 microns. 
     
     
         130 . The process of  claim 123 , wherein said insoluble supports having said precipitation surfaces comprise a powder of diatomaceous earth. 
     
     
         131 . The process of  claim 119 , wherein said medium is inert to any of said anti-solvent, said polymer-containing fluid, and said polymer. 
     
     
         132 . The process of  claim 119 , wherein the polymer in said polymer-containing fluid is miscible in said anti-solvent. 
     
     
         133 . The process of  claim 119 , wherein said polymer-containing fluid is at least partially miscible in said anti-solvent. 
     
     
         134 . The process of  claim 119 , wherein the polymer in said polymer-containing fluid comprises a plurality of cyclodextrin moieties. 
     
     
         135 . The process of  claim 134 , wherein at least one of said cyclodextrin moieties comprises α-cyclodextrin. 
     
     
         136 . The process of  claim 134 , wherein at least one of said cyclodextrin moieties comprises β-cyclodextrin. 
     
     
         137 . The process of  claim 134 , wherein at least one of said cyclodextrin moieties comprises γ-cyclodextrin. 
     
     
         138 . The process of  claim 134 , wherein said cyclodextrin moieties form any of a linear and branched polymer. 
     
     
         139 . The process of  claim 119 , wherein the polymer in said polymer-containing fluid comprises a therapeutic agent covalently attached thereto. 
     
     
         140 . The process of  claim 139 , wherein said therapeutic agent is any of anti-cancer agent, an anti-inflammatory agent, or a cardiovascular active agent. 
     
     
         141 . The process of  claim 139 , wherein said therapeutic agent is any of a taxane, an epothilone, a boronic acid proteasome inhibitor, and an anti-biotic. 
     
     
         142 . The process of  claim 139 , wherein said therapeutic agent is an anti-metabolite. 
     
     
         143 . The process of  claim 119 , wherein said polymer comprises a bioactive agent. 
     
     
         144 . The process of  claim 143 , wherein said bioactive agent comprises any of a diagnostic agent and an adjuvant. 
     
     
         145 . The process of  claim 119 , wherein said polymer-containing fluid comprises acetone, ether, alcohol, tetrahydrofuran, 2-pyrrolidone, N-methyl-2-pyrrolidone, dimethylformamide, dimethylacetamide, methyl acetate, ethyl formate, methyl ethyl ketone, methyl isobutyl ketone, methyl propyl ketone, isopropyl ketone, isopropyl acetate, acetonitrile, dimethyl sulfoxide, or a combination thereof. 
     
     
         146 . The process of  claim 119 , wherein said anti-solvent comprises any of an organic solvent or a mixture of two or more organic solvents. 
     
     
         147 . The process of  claim 119 , wherein said anti-solvent comprises methanol, ethanol, acetone, n-propanol, isopropanol, n-butanol, ethyl ether, methyl isobutyl ketone or ethyl acetate or a combination thereof. 
     
     
         148 . The process  claim 119 , further comprising filtering a mixture of said particles (e.g., nanoparticles) and said solvent. 
     
     
         149 . The process of  claim 148 , wherein said filtering step comprises utilizing tangential flow filtration. 
     
     
         150 . The process of  claim 119 , further comprising collecting said polymeric particles (e.g., nanoparticles). 
     
     
         151 . The process of  claim 150 , further comprising lyophilizing said collected polymeric particles (e.g., nanoparticles). 
     
     
         152 . The process of  claim 119 , wherein said polymeric particles (e.g., nanoparticles) exhibit an average particle size less than about 1 micron. 
     
     
         153 . The process of  claim 119 , wherein said polymeric nanoparticles exhibit an average particle size less than about 500 nm. 
     
     
         154 . The process of  claim 119 , wherein said polymeric nanoparticles exhibit an average particle size less than about 200 nm. 
     
     
         155 . The process of  claim 119 , wherein said polymeric nanoparticles exhibit an average particle size less than about 100 nm. 
     
     
         156 . The process of  claim 119 , wherein said polymeric nanoparticles exhibit an average particle size less than about 50 nm. 
     
     
         157 . The process of  claim 119 , wherein said polymeric nanoparticles exhibit an average particle size in a range of about 5 nm to about 200 nm. 
     
     
         158 . The process of  claim 119 , wherein said particles exhibit a polydispersity index in a range of about 0.1 to about 1. 
     
     
         159 . A plurality of polymeric particles (e.g., nanoparticles) produced according to process of  claim 119 . 
     
     
         160 . The plurality of polymeric particles (e.g., nanoparticles) of  claim 159 , wherein said plurality of particles includes at least about 100 grams of the particles. 
     
     
         161 . The plurality of polymeric particles (e.g., nanoparticles) of  claim 159 , wherein said plurality of particles includes at least about 200 grams of the particles. 
     
     
         162 . The plurality of polymeric nanoparticles of  claim 159 , wherein said nanoparticles exhibit an average particle size less than about 200 nm. 
     
     
         163 . The plurality of polymeric nanoparticles of  claim 159 , wherein said nanoparticles exhibit an average particle size less than about 100 nm. 
     
     
         164 . The plurality of polymeric nanoparticles of  claim 159 , wherein said nanoparticles exhibit an average particle size less than about 50 nm. 
     
     
         165 . The plurality of polymeric nanoparticles of  claim 159 , wherein said nanoparticles exhibit an average particle size in a range of about 5 nm to about 200 nm. 
     
     
         166 . The plurality of polymeric nanoparticles of  claim 159 , wherein said nanoparticles exhibit a polydispersity index in a range of about 0.1 to about 0.5. 
     
     
         167 . The process of any of  claim 1 - 41  or  57 - 70  further comprising drying the precipitation surfaces on which precipitation of at least a portion of the polymer has occurred. 
     
     
         168 . A product produced by the process of any of  claim 1 - 41 ,  57 - 70 ,  85 - 91 , or  167 . 
     
     
         169 . A preparation comprising a polymer precipitated onto an insoluble support, wherein said polymer is a cyclodextrin containing polymer. 
     
     
         170 . The preparation of  claim 169 , wherein said polymer comprises one or more therapeutic agents covalently attached thereto. 
     
     
         171 . The preparation of  claim 169 , wherein said preparation contains less than 50, 40, 30, 20, 10, 5, or 1% by weight solvent. 
     
     
         172 . The preparation of  claim 171 , wherein said solvent is DMF or IPA (isopropyl alcohol). 
     
     
         173 . The preparation of  claim 169 , wherein the preparation comprising the insoluble support comprises a plurality of particulate solids (e.g., Celite). 
     
     
         174 . The preparation of  claim 169 , wherein the preparation comprising said polymer precipitated onto an insoluble support is disposed in the vessel in which aid precipitation occurred. 
     
     
         175 . The preparation of  claim 169 , wherein said the preparation comprising polymer precipitated onto an insoluble support is not disposed in the same vessel in which aid precipitation occurred. 
     
     
         176 . A method of making a particle comprising:
 a) providing a preparation comprising a preparation of solid supports having a polymer precipitated thereon; and   b) placing said preparation in contact with a stripping liquid to strip at least a portion of said precipitated polymer from the precipitation surfaces so as to form a plurality of polymeric particles (e.g., nanoparticles) in said stripping liquid.   
     
     
         177 . The method of  claim 176 , wherein at least 1, 2, 3, 5, or 10 hours, or at least 1, 2, 5, 10, 20, or 30 days, elapse between the precipitation of polymer on said precipitation surfaces and providing said preparation. 
     
     
         178 . The method of  claim 176 , wherein less than 1, 2, 3, 5, or 10 hours, or less than 1, 2, 5, 10, 20, or 30 days, elapse between the precipitation of polymer on said precipitation surfaces and step b.

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