Polymer nanoparticle freeze-dried product, and preparation method therefor

A method for preparing lyophilizate of polymeric nanoparticle by lyophilization process of a solution of polymeric nanoparticle,

• wherein the solution of polymeric nanoparticle comprises an amphiphilic block copolymer consisting of a hydrophilic block (A) and a hydrophobic block (B) in A-B, A-B-A or B-A-B form;
• a polylactic acid derivative having carboxyl terminal group;
• a lyophilization aid;
• and a poorly water-soluble drug which is paclitaxel or docetaxel,
• wherein the solution of polymeric nanoparticle has a polymer concentration of 120 mg/ml or lower,
• wherein the lyophilization process comprises:
• a) a first freezing step where the solution of polymeric nanoparticle is frozen to a temperature in the range of −10 to −45° C.;
• b) an annealing step where the resulting product of the first freezing is heated to a temperature in the range of −25 to 0° C.;
• c) a second freezing step where the resulting product of the annealing is frozen to a temperature in the range of −10 to −45° C.;
• d) a primary drying step where the resulting product of the second freezing is dried at a temperature of lower than 0° C. under reduced pressure;
• e) a secondary drying step where the resulting product of the primary drying is dried at a temperature of 0° C. or higher under reduced pressure;
• and
• f) introducing the resulting product into a vial, and sealing the vial in vacuo;
• and
• wherein the lyophilizate of polymeric nanoparticle is reconstituted within 5 minutes when reconstituted with an aqueous solvent under atmospheric pressure;
• the amount of the lyophilization aid is 10 to 60% by weight, based on the total dry weight of the lyophilizate of polymeric nanoparticle;
• the hydrophilic block (A) is selected from the group consisting of polyethylene glycol, monomethoxypolyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol and polyacrylamide;
• and the hydrophobic block (B) is selected from the group consisting of polylactide, polyglycolide, polydioxan-2-one, polycaprolactone, polylactic-co-glycolide, polylactic-co-caprolactone, polylactic-co-dioxan-2-one and polyglycolic-co-caprolactone;
• the hydrophilic block (A) has a number average molecular weight of 500 to 50,000 Daltons;
• and the hydrophobic block (B) has a number average molecular weight of 500 to 50,000 Daltons;
• the polylactic acid derivative having carboxyl terminal group has a number average molecular weight of 500 to 5,000 Daltons;
• and
• the lyophilizate has an average pore size of 70 μm or greater.