Non-Aqueous High Concentration Reduced Viscosity Suspension Formulations
The present invention relates to non-aqueous high concentration reduced viscosity suspension formulations and methods of making and using them.
1 . A non-aqueous high concentration suspension formulation, comprising:
a. a vehicle, comprising a hydrophobic agent and a viscosity-reducing agent; and
b. a bioactive molecule.
2 . The formulation of claim 1 , wherein the hydrophobic agent is sesame oil.
3 . The formulation of claim 1 , wherein the viscosity-reducing agent is ethyl oleate, linoleic acid, propionic acid, triethyl citrate, isopropyl alcohol, ethanol, diethyl sebacate, or isopropyl myristate.
4 . The formulation of claim 1 , wherein the amount of the viscosity-reducing agent in the vehicle is between 0.2%-85% by volume (% v/v) of the vehicle.
5 . The formulation of claim 1 , wherein the bioactive molecule is present at from about 0.5% to about 50% by weight (% w/w) of the formulation.
6 . The formulation of claim 1 , wherein the injection force of the formulation is equal to or less than 45 Newton (N), wherein the injection force is measured using a 1 mL rigid needle shield glass syringe having a 0.25 inch inside diameter, equipped with a 0.5 inch 26½ gauge needle at a 250 mm/min injection speed.
7 . The formulation of claim 1 , wherein the particle size of the bioactive molecule is between 2 μm-13 μm.
8 . The formulation of claim 1 , wherein the bioactive molecule is a monoclonal antibody.
9 . The formulation of claim 1 which is stable at 40° C. for at least one month.
10 . A non-aqueous high concentration suspension formulation, comprising:
a. a vehicle comprising sesame oil and ethyl oleate; and
b. a bioactive molecule.
11 . The formulation of claim 10 , wherein the amount of the ethyl oleate in the vehicle is between 0.2%-85% by volume (% v/v) of the vehicle.
12 . The formulation of claim 10 , wherein the bioactive molecule is present at from about 0.5% to about 50% by weight (% w/w) of the formulation.
13 . The formulation of claim 1 , wherein the injection force of the formulation is equal to or less than 45 Newton (N), wherein the injection force is measured using a 1 mL rigid needle shield glass syringe having a 0.25 inch inside diameter, equipped with a 0.5 inch 26½ gauge needle at a 250 mm/min injection speed.
14 . The formulation of claim 10 , wherein the size of the bioactive molecule is between 2 μm-13 μm.
15 . The formulation of claim 10 , wherein the protein is a monoclonal antibody.
16 . A method of reducing an injection force to about 45 Newton (N) or less of a formulation containing ≧50 mg/ml of a protein in a vehicle comprising a hydrophobic agent, comprising:
a. adding at least 28% by volume of a viscosity reducing agent into the vehicle comprising a hydrophobic agent; or
b. utilizing protein particles having particle size between about 2 μm-13 μm to prepare the formulation,
wherein the injection force is measured using a 1 mL rigid needle shield glass syringe having a 0.25 inch inside diameter, equipped with a 0.5 inch 26½ gauge needle at a 250 mm/min injection speed.
17 . The method of claim 16 , wherein the hydrophobic vehicle is sesame oil and the viscosity reducing agent is ethyl oleate.
18 . A method of making a non-aqueous high concentration suspension formulation of a bioactive molecule, comprising
a. providing a bioactive molecule;
b. providing a hydrophobic agent;
c. providing a viscosity reducing agent;
d. mixing the hydrophobic agent and the viscosity reducing agent to form a vehicle; and
e. adding the bioactive molecule into the vehicle formed in step d. at a concentration of equal to or more than 50 mg/mL.