Methods for micronization of hydrophobic drugs
The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.
1 - 49 . (canceled)
50 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, wherein the first solvent is free of polymer, wherein the hydrophobic agent and the solvent form a mixture having a continuous phase,
introducing a second solvent into the mixture, and
introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifungal, antihypertensive, anti-infective, antimicrobial, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
51 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, wherein the first solvent is free of polymer, wherein the hydrophobic agent and the solvent form a mixture having a continuous phase,
introducing a second solvent into the mixture, and
introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
52 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, wherein the first solvent is free of polymer, wherein the hydrophobic agent and the solvent form a mixture having a continuous phase,
introducing a second solvent into the mixture, and
introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
53 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, wherein the first solvent is free of polymer, wherein the hydrophobic agent and the solvent form a mixture having a continuous phase,
introducing a second solvent into the mixture, and
introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
54 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, wherein the first solvent is free of polymer, wherein the hydrophobic agent and the solvent form a mixture having a continuous phase,
introducing a second solvent into the mixture, and
introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is a dye or an imaging agent.
55 . The method of claim 51 , wherein the anti-cancer agent is Paclitaxel.
56 . The method of claim 50 , further comprising preparing microparticles by spray drying the micronized hydrophobic agent.
57 . The method of claim 50 , further comprising preparing microparticles by performing phase inversion nanoencapsulation (PIN) on the micronized hydrophobic agent.
58 . The method of claim 50 , wherein the second solvent is an alcohol.
59 . The method of claim 50 , wherein greater than 90% of the micronized hydrophobic agent have a particle size less than 1 micron.
60 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, with a polymer, wherein the hydrophobic agent and the first solvent form a mixture having a continuous phase, introducing a second solvent into the mixture, and introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifungal, anti-infective, antimicrobial, antihypertensive, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
61 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, with a polymer, wherein the hydrophobic agent and the first solvent form a mixture having a continuous phase, introducing a second solvent into the mixture, and introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
62 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, with a polymer, wherein the hydrophobic agent and the first solvent form a mixture having a continuous phase, introducing a second solvent into the mixture, and introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
63 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, with a polymer, wherein the hydrophobic agent and the first solvent form a mixture having a continuous phase, introducing a second solvent into the mixture, and introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
64 . A method for micronizing a hydrophobic agent, comprising:
dissolving a hydrophobic agent in an effective amount of a first solvent, with a polymer, wherein the hydrophobic agent and the first solvent form a mixture having a continuous phase, introducing a second solvent into the mixture, and introducing an aqueous solution into the mixture wherein the aqueous solution causes precipitation of the hydrophobic agent to produce a composition of micronized hydrophobic agent having an average particle size of 1 micron or less, and wherein the hydrophobic agent is a dye or an imaging agent.
65 . The method of claim 61 , wherein the anti-cancer agent is Paclitaxel.
66 . The method of claim 60 , wherein the preparation contains less than 5% polymer.
67 . The method of claim 60 , further comprising preparing microparticles by performing phase inversion nanoencapsulation on the micronized hydrophobic agent.
68 . The method of claim 60 , wherein the second solvent is an alcohol.
69 . The method of claim 60 , wherein greater than 90% of the micronized hydrophobic agent have a particle size less than 1 micron.
70 . A preparation of micronized hydrophobic agent prepared according to the method of claim 50 .
71 . A preparation of micronized hydrophobic agent prepared according to the method of claim 60 .
72 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer carrier and is free of surfactant, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifingal, antihypertensive, anti-infective, antimicrobial, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
73 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer carrier and is free of surfactant, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
74 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer carrier and is free of surfactant, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
75 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer carrier and is free of surfactant, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
76 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer carrier and is free of surfactant, and wherein the hydrophobic agent is a dye or an imaging agent.
77 . The composition of claim 73 , wherein the anti-cancer agent is Paclitaxel.
78 . The composition of claim 72 , wherein the wherein the preparation is free of polymer carrier.
79 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is free of polymer carrier and wherein the crystallinity of the micronized hydrophobic agent is at least 50% of the crystallinity of the non-micronized hydrophobic agent, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifungal, antihypertensive, anti-infective, antimicrobial, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
80 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is free of polymer carrier and wherein the crystallinity of the micronized hydrophobic agent is at least 50% of the crystallinity of the non-micronized hydrophobic agent, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
81 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is free of polymer carrier and wherein the crystallinity of the micronized hydrophobic agent is at least 50% of the crystallinity of the non-micronized hydrophobic agent, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
82 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is free of polymer carrier and wherein the crystallinity of the micronized hydrophobic agent is at least 50% of the crystallinity of the non-micronized hydrophobic agent, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
83 . A composition, comprising a preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is free of polymer carrier and wherein the crystallinity of the micronized hydrophobic agent is at least 50% of the crystallinity of the non-micronized hydrophobic agent, and wherein the hydrophobic agent is a dye or an imaging agent.
84 . The composition of claim 80 , wherein the anti-cancer agent is Paclitaxel.
85 . The composition of claim 79 , wherein the crystallinity is at least 75%.
86 . The composition of claim 79 , wherein the crystallinity is greater than 90%.
87 . A method for delivering an agent to a subject, comprising:
orally administering a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifungal, antihypertensive, anti-infective, antimicrobial, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
88 . A method for delivering an agent to a subject, comprising:
orally administering a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
89 . A method for delivering an agent to a subject, comprising:
orally administering a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
90 . A method for delivering an agent to a subject, comprising:
orally administering a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
91 . A method for delivering an agent to a subject, comprising:
orally administering a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is a dye or an imaging agent.
92 . The method of claim 88 , wherein the anti-cancer agent is Paclitaxel.
93 . The method of claim 87 , wherein the bioactivity of the hydrophobic agent is retained.
94 . The method of claim 87 , wherein there is at least a 5% increase in the relative bioavailability of the micronized hydrophobic agent as compared to the non-micronized hydrophobic agent.
95 . The method of claim 87 , wherein the preparation is free of polymer.
96 . The method of claim 87 , wherein the micronized hydrophobic agent is microencapsulated by phase inversion nanoencapsulation.
97 . A method for delivering an agent to a subject, comprising:
administering microparticles of a micronized hydrophobic agent encapsulated by phase inversion nanoencapsulation having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifungal, antihypertensive, anti-infective, antimicrobial, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
98 . A method for delivering an agent to a subject, comprising:
administering microparticles of a micronized hydrophobic agent encapsulated by phase inversion nanoencapsulation having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
99 . A method for delivering an agent to a subject, comprising:
administering microparticles of a micronized hydrophobic agent encapsulated by phase inversion nanoencapsulation having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
100 . A method for delivering an agent to a subject, comprising:
administering microparticles of a micronized hydrophobic agent encapsulated by phase inversion nanoencapsulation having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
101 . A method for delivering an agent to a subject, comprising:
administering microparticles of a micronized hydrophobic agent encapsulated by phase inversion nanoencapsulation having an average particle size of less than 1 micron, wherein the preparation is composed of less than 5% polymer and is free of surfactant, and wherein the hydrophobic agent is a dye or an imaging agent.
102 . The method of claim 98 , wherein the anti-cancer agent is Paclitaxel.
103 . The method of claim 97 , wherein the microparticles are administered orally.
104 . The method of claim 97 , wherein the bioactivity of the hydrophobic agent is retained.
105 . The method of claim 97 , wherein there is at least a 5% increase in the relative bioavailability of the micronized hydrophobic agent as compared to the non-encapsulated micronized hydrophobic agent.
106 . The method of claim 97 , wherein the preparation is free of polymer.
107 . A method for achieving 100% bioactivity comprising:
orally administering to the subject a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein 100% of the orally administered agent is bioactive, and wherein the hydrophobic agent is selected from the group consisting of anticonvulsant, antidiabetic, antifingal, antihypertensive, anti-infective, antimicrobial, antimycotic, antineoplastic, anti-cancer, anti-epileptic, antiparasitic, antiproliferative, antiviral, blood glucose regulator, diuretic, hormone, hypoglycemic, hypotensive, immunomodulator, immunoregulator, immunosuppressant, mood regulator, psychotropic, dyes, and imaging agents.
108 . A method for achieving 100% bioactivity comprising:
orally administering to the subject a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein 100% of the orally administered agent is bioactive, and wherein the hydrophobic agent is an antineoplastic, anti-cancer, or antiproliferative agent.
109 . A method for achieving 100% bioactivity comprising:
orally administering to the subject a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein 100% of the orally administered agent is bioactive, and wherein the hydrophobic agent is an antifungal or antimycotic agent.
110 . A method for achieving 100% bioactivity comprising:
orally administering to the subject a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein 100% of the orally administered agent is bioactive, and wherein the hydrophobic agent is an anti-infective or antimicrobial agent.
111 . A method for achieving 100% bioactivity comprising:
orally administering to the subject a solid preparation of micronized hydrophobic agent having an average particle size of less than 1 micron, wherein 100% of the orally administered agent is bioactive, and wherein the hydrophobic agent is a dye or an imaging agent.
112 . The method of claim 108 , wherein the anti-cancer agent is Paclitaxel.
113 . The method of claim 107 , wherein the preparation is composed of less than 5% polymer and is free of surfactant.
114 . The method of claim 107 , wherein the preparation is free of polymer.