HIGH DELIVERY RATES FOR LIPID BASED DRUG FORMULATIONS, AND METHODS OF TREATMENT THEREOF
Provided is a method of preparing lipid based drug formulations with low lipid/drug ratios using coacervation techniques. Also provided are methods of delivering such lipid based drug formulations at high delivery rates, and methods of treating patients with pulmonary diseases comprising administering such lipid based drug formulations.
1 .- 25 . (canceled)
26 . A lipid antiinfective formulation comprising an antiinfective complexed to or encapsulated by a lipid component, wherein the lipid component is net neutral and comprises a phospholipid and a sterol, and the lipid component to antiinfective weight ratio in the formulation is 0.40:1 to 0.49:1.
27 . The lipid antiinfective formulation of claim 26 , wherein the phospholipid is dipalmitoylphosphatidylcholine (DPPC).
28 . The lipid antiinfective formulation of claim 26 , wherein the sterol is cholesterol.
29 . The lipid antiinfective formulation of claim 27 , wherein the sterol is cholesterol.
30 . The lipid antiinfective formulation of claim 26 , wherein the lipid component is present as liposomes and the antiinfective is encapsulated by the liposomes.
31 . The lipid antiinfective formulation of claim 27 , wherein the lipid component is present as liposomes and the antiinfective is encapsulated by the liposomes.
32 . The lipid antiinfective formulation of claim 28 , wherein the lipid component is present as liposomes and the antiinfective is encapsulated by the liposomes.
33 . The lipid antiinfective formulation of claim 29 , wherein the lipid component is present as liposomes and the antiinfective is encapsulated by the liposomes.
34 . The lipid antiinfective formulation of claim 26 , wherein the antiinfective is an aminoglycoside, a tetracycline, a sulfonamide, p-aminobenzoic acid, a diaminopyrimidine, a quinolone, a β-lactam, a β-lactam and a β-lactamase inhibitor, chloraphenicol, a macrolide, a penicillin, a cephalosporin, linomycin, clindamycin, spectinomycin, polymyxin B, colistin, vancomycin, bacitracin, isoniazid, rifampin, ethambutol, ethionamide, aminosalicylic acid, cycloserine, capreomycin, a sulfone, clofazimine, thalidomide, a polyene antifungal, flucytosine, imidazole, triazole, griseofulvin, terconazole, butoconazole ciclopirax, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine, or a combination thereof.
35 . The lipid antiinfective formulation of claim 33 , wherein the antiinfective is an aminoglycoside, a tetracycline, a sulfonamide, p-aminobenzoic acid, a diaminopyrimidine, a quinolone, a β-lactam, a β-lactam and a β-lactamase inhibitor, chloraphenicol, a macrolide, a penicillin, a cephalosporin, linomycin, clindamycin, spectinomycin, polymyxin B, colistin, vancomycin, bacitracin, isoniazid, rifampin, ethambutol, ethionamide, aminosalicylic acid, cycloserine, capreomycin, a sulfone, clofazimine, thalidomide, a polyene antifungal, flucytosine, imidazole, triazole, griseofulvin, terconazole, butoconazole ciclopirax, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine, or a combination thereof.
36 . The lipid antiinfective formulation of claim 26 , wherein the antiinfective is an aminoglycoside.
37 . The lipid antiinfective formulation of claim 27 , wherein the antiinfective is an aminoglycoside.
38 . The lipid antiinfective formulation of claim 28 , wherein the antiinfective is an aminoglycoside.
39 . The lipid antiinfective formulation of claim 29 , wherein the antiinfective is an aminoglycoside.
40 . The lipid antiinfective formulation of claim 30 , wherein the antiinfective is an aminoglycoside.
41 . The lipid antiinfective formulation of claim 31 , wherein the antiinfective is an aminoglycoside.
42 . The lipid antiinfective formulation of claim 32 , wherein the antiinfective is an aminoglycoside.
43 . The lipid antiinfective formulation of claim 33 , wherein the antiinfective is an aminoglycoside.
44 . The lipid antiinfective formulation of claim 36 , wherein the aminoglycoside is amikacin.
45 . The lipid antiinfective formulation of claim 37 , wherein the aminoglycoside is amikacin.
46 . The lipid antiinfective formulation of claim 38 , wherein the aminoglycoside is amikacin.
47 . The lipid antiinfective formulation of claim 39 , wherein the aminoglycoside is amikacin.
48 . The lipid antiinfective formulation of claim 40 , wherein the aminoglycoside is amikacin.
49 . The lipid antiinfective formulation of claim 41 , wherein the aminoglycoside is amikacin.
50 . The lipid antiinfective formulation of claim 42 , wherein the aminoglycoside is amikacin.
51 . The lipid antiinfective formulation of claim 43 , wherein the aminoglycoside is amikacin.
52 . A method of treating a pulmonary infection in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation comprising an antiinfective complexed to or encapsulated by a lipid component, wherein the lipid component is net neutral and comprises a phospholipid and a sterol, and the lipid component to antiinfective weight ratio in the formulation is 0.40:1 to 0.49:1.
53 . The method of claim 52 , wherein the administering occurs via nebulizing the lipid antiinfective formulation at a rate of 10 to 25 mg/min.
54 . The method of claim 52 , wherein the lipid component is present as liposomes and the antiinfective is encapsulated by the liposomes.
55 . The method of claim 52 , wherein the phospholipid is dipalmitoylphosphatidylcholine (DPPC).
56 . The method of claim 53 , wherein the phospholipid is dipalmitoylphosphatidylcholine (DPPC).
57 . The method of claim 54 , wherein the phospholipid is dipalmitoylphosphatidylcholine (DPPC).
58 . The method of claim 55 , wherein the sterol is cholesterol.
59 . The method of claim 56 , wherein the sterol is cholesterol.
60 . The method of claim 57 , wherein the sterol is cholesterol.
61 . The method of claim 58 , wherein the pulmonary infection is a Pseudomonas infection.
62 . The method of claim 59 , wherein the pulmonary infection is a Pseudomonas infection.
63 . The method of claim 60 , wherein the pulmonary infection is a Pseudomonas infection.
64 . The method of claim 58 , wherein the pulmonary infection is a mycobacterial infection.
65 . The method of claim 59 , wherein the pulmonary infection is a mycobacterial infection.
66 . The method of claim 60 , wherein the pulmonary infection is a mycobacterial infection.
67 . The method of claim 52 , wherein the antiinfective is an aminoglycoside, a tetracycline, a sulfonamide, p-aminobenzoic acid, a diaminopyrimidine, a quinolone, a β-lactam, a β-lactam and a β-lactamase inhibitor, chloraphenicol, a macrolide, a penicillin, a cephalosporin, linomycin, clindamycin, spectinomycin, polymyxin B, colistin, vancomycin, bacitracin, isoniazid, rifampin, ethambutol, ethionamide, aminosalicylic acid, cycloserine, capreomycin, a sulfone, clofazimine, thalidomide, a polyene antifungal, flucytosine, imidazole, triazole, griseofulvin, terconazole, butoconazole ciclopirax, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine, or a combination thereof.
68 . The method of claim 54 , wherein the antiinfective is an aminoglycoside, a tetracycline, a sulfonamide, p-aminobenzoic acid, a diaminopyrimidine, a quinolone, a β-lactam, a β-lactam and a β-lactamase inhibitor, chloraphenicol, a macrolide, a penicillin, a cephalosporin, linomycin, clindamycin, spectinomycin, polymyxin B, colistin, vancomycin, bacitracin, isoniazid, rifampin, ethambutol, ethionamide, aminosalicylic acid, cycloserine, capreomycin, a sulfone, clofazimine, thalidomide, a polyene antifungal, flucytosine, imidazole, triazole, griseofulvin, terconazole, butoconazole ciclopirax, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine, or a combination thereof.
69 . The method of claim 60 , wherein the antiinfective is an aminoglycoside, a tetracycline, a sulfonamide, p-aminobenzoic acid, a diaminopyrimidine, a quinolone, a β-lactam, a β-lactam and a β-lactamase inhibitor, chloraphenicol, a macrolide, a penicillin, a cephalosporin, linomycin, clindamycin, spectinomycin, polymyxin B, colistin, vancomycin, bacitracin, isoniazid, rifampin, ethambutol, ethionamide, aminosalicylic acid, cycloserine, capreomycin, a sulfone, clofazimine, thalidomide, a polyene antifungal, flucytosine, imidazole, triazole, griseofulvin, terconazole, butoconazole ciclopirax, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine, or a combination thereof.
70 . The method of claim 67 , wherein the antiinfective is an aminoglycoside.
71 . The method of claim 68 , wherein the antiinfective is an aminoglycoside.
72 . The method of claim 69 , wherein the antiinfective is an aminoglycoside.
73 . The method of claim 70 , wherein the aminoglycoside is amikacin.
74 . The method of claim 71 , wherein the aminoglycoside is amikacin.
75 . The method of claim 72 , wherein the aminoglycoside is amikacin.