Process for preparing therapeutic compositions containing nanoparticles
AssigneeNanoSystems L.L.C.
InventorsH. William Bosch, Donna M. Marcera, Ronald L. Mueller, Jon R. Swanson, Dinesh S. Mishra
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Abstract
A process of preparing nanoparticulate drug substances comprising the steps of: preparing a premix of the drug substance and a surface modifier, and subjecting the premix to mechanical means to reduce the particle size of the drug substance, the mechanical means producing shear, impact, cavitation and attrition.
Claims20
A process for preparing particles consisting essentially of 99.9-10% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml, said drug substance having a non-crosslinked surface modifier adsorbed on the surface thereof in an amount of (). 1-9()% by weight and sufficient to maintain an effective average particle size of less than about 400 nm, said process comprises the steps of:
- a) preparing a promix of said crystalline drug substance having a particle size of less than about 100 .mu.m and said surface modifier by mixing them in a liquid dispersion medium being selected form the group consisting of water, aqueous salt solutions, safflower oil, ethanol, t-butanol, hexane and glycol;
- b) transferring said premix to a microfluidizer having an interaction chamber capable of producing shear, impact, cavitation and attrition forces;
- c) subjecting said promix to said forces at a temperature not exceeding 40.degree. C. and a fluid pressure of from about 3,000 to about 30,000 psi by passing said premix through said interaction chamber to reduce the particle size of said drug substance and to obtain a homogeneous slurry thereof:
- d) collecting all the slurry from said interaction chamber into a receiving tank;
- c) reintroducing said slurry m said receiving tank into said interaction chamber to further subject said slurry to said forces and thereby to decrease the effective average particle size of said drub substance:
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- f) repeating said collection and reintroduction steps until said drug substance is reduced to an effective average particle size of less than about 400 nm.
A process for preparing particles consisting essentially of 99.9-10% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml, said drug substance having a non-crosslinked surface modifier adsorbed on the surface thereof in an amount of 0.1-90% by weight and sufficient to maintain an effective average particle size of less than about 400 nm, said process comprises the steps of:
- a) preparing a promix of said crystalline drug substance having a particle size of less than about 100 .mu.m and said surface modifier by mixing them in a liquid dispersion medium being selected form the group consisting of water, aqueous salt solutions, safflower oil, ethanol, t-butanol, hexane and glycol;
- b) transferring said premix to a microfluidizer having an interaction chamber capable producing shear, impact, cavitation and attrition forces;
- c) subjecting said premix to said forces at a temperature not exceeding 40.degree. C. and a fluid pressure of from about 3,000 to about 30,000 psi by passing said premix through said interaction chamber to reduce the particle size of said drug substance and to obtain a homogeneous slurry thereof;
- d) collecting a portion of the slurry from said interaction chamber into a receiving tank:
- c) reintroducing said portion of the slurry into said interaction chamber;
- repeating said collection and reintroduction steps in a continuous process until said drug substance is reduced to an effective average particle size of less than about 400 nm.
Dependencies are inferred from the claim text.