Particle Formation And Morphology
The present disclosure relates to compositions and methods that enable the formation of pharmaceutically relevant particles that can be used for therapy. In particular, the methods disclosed herein allow the controlled formation of circular particles having low internal void spaces comprising bioactive therapeutic agents.
1 . (canceled)
2 . A method of controlling the morphology of particles, the method comprising:
a) providing droplets comprising a first liquid and an agent;
b) contacting the droplets with a second liquid under a specified Peclet number;
c) allowing the droplets to dry; and
d) removing the first and second liquids,
wherein the specified Peclet number controls the morphology of the particles, wherein the morphology is selected from the group consisting of sphericity, roundness, surface roughness, and internal void spaces.
3 . The method of claim 2 , wherein the first or second liquid further comprises a plasticizer.
4 . The method of claim 3 , wherein the plasticizer is sucrose, xylitol, sorbitol, fructose, triglyceride, pectin, glycerol, triethylcitrate, ethyl acetate, citric acid, oleic acid, hydroxypropyl cellulose, methyl pyrrolidone polyethylene glycol, polypropylene glycol, polysorbate 20, polysorbate 60, polysorbate 80, fatty acid ester of sorbitol, diethyl phthalate and other phthalate derivatives, castor oil, triacetin, water, chlorpheniramine, 1-butyl-3-methyl imidazolium dioctyl sulfosuccinate, hexyl acetate, 2-ethylhexyl acetate, triethyl citrate, dibutyl sebacate, benzyl alcohol, benzyl benzoate, dimethylacetamide, or a combination thereof.
5 . The method of claim 2 , wherein the agent is a therapeutic biologic.
6 . The method of claim 2 , wherein the agent is an antibody.
7 . The method of claim 5 , wherein the particles have greater than about 60% therapeutic biologic by weight.
8 . The method of claim 2 , wherein the morphology is sphericity.
9 . The method of claim 2 , wherein the sphericity of the particle is from about 0.80 to about 1.00.
10 . The method of claim 2 , wherein the first liquid is water, 0.9% saline, lactated Ringer's solution, buffers, dextrose 5%, or a combination thereof.
11 . The method of claim 2 , wherein the first liquid is water.
12 . The method of claim 2 , wherein the concentration of the agent in the first liquid is from about 10 mg/ml to about 500 mg/mL.
13 . The method of claim 2 , wherein the first liquid further comprises a surfactant.
14 . The method of claim 2 , wherein the second liquid is an organic solvent.
15 . The method of claim 14 , wherein the organic solvent is benzyl alcohol, benzyl benzoate, castor oil, coconut oil, corn oil, cottonseed oil, fish oil, grape seed oil, hazelnut oil, hydrogenated palm seed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, sunflower oil, vegetable oil, walnut oil, polyethylene glycol, glycofurol, acetone, diglyme, dimethylacetamide, dimethyl isosorbide, dimethyl sulfoxide, ethanol, ethyl acetate, butyl acetate, ethyl ether, ethyl lactate, isopropyl acetate, methyl acetate, methyl isobutyl ketone, methyl tert-butyl ether, N-methyl pyrrolidone, perfluorodecalin, 2-pyrrolidone, trigylcerides, tetrahydrofurfuryl alcohol, triglycerides of the fractionated plant fatty acids C8 and C10 (e.g., MIGLYOL® 810 and MIGLOYL® 812N), propylene glycol diesters of saturated plant fatty acids C8 and C10 (e.g., MIGLYOL® 840), ethyl oleate, ethyl caprate, dibutyl adipate, fatty acid esters, hexanoic acid, octanoic acid, triacetin, diethyl glycol monoether, gamma-butyrolactone, eugenol, clove bud oil, citral, limonene, or a combination thereof.
16 . The method of claim 14 , wherein the organic solvent is ethyl acetate or butyl acetate.
17 . The method of claim 2 , wherein the Peclet number of step b) is less than about 500.
18 . The method of claim 2 , wherein the Peclet number of step b) is less than about 10.
19 . The method of claim 2 , wherein the droplets are contacted with the second liquid in an apparatus.
20 . The method of claim 19 , wherein the apparatus is a microfluidic device, a tube-in-tube assembly, or a homogenizer.
21 . The method of claim 20 , wherein the apparatus is a microfluidic device and the droplets are regularly spaced in the microfluidic device.