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 . A method of delivering a lipid based drug formulation at a rate of 10 to 25 mg/min of drug comprising nebulizing a lipid based drug formulation with a lipid to drug (L/D) ratio of 0.40 to 0.49 using a compressor pressure of 20 to 40 psi.
2 . The method of claim 1 , wherein the entrapped drug retention is greater than 45%.
3 . The method of claim 1 , wherein the lipid is a mixture of a phospholipid and a sterol.
4 . The method of claim 3 , wherein the phospholipid is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
5 . The method of claim 4 , wherein the DPPC:cholesterol ratio is 2:1 by weight.
6 . The method of claim 1 , wherein the drug is an antiinfective.
7 . The method of claim 6 , wherein the antiinfective is selected from the following: 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, penicillins, cephalosporins, corticosteroid, prostaglandin, 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 combination thereof.
8 . The method of claim 7 , wherein the antiinfective is an aminoglycoside.
9 . The method of claim 8 , wherein the aminoglycoside is amikacin.
10 . The method of claim 8 , wherein the aminoglycoside is tobramicin.
11 . The method of claim 8 , wherein the aminoglycoside is gentamicin.
12 . The method of claim 1 , wherein the lipid based formulation is a liposome.
13 . A method of treating a patient for a pulmonary infection comprising administering to the patient in need thereof a therapeutically effective amount of a lipid based drug formulation having a L/D ratio of 0.40 to 0.49 and wherein the drug is an antiinfective.
14 . The method of claim 13 , wherein the antiinfective is an aminoglycoside.
15 . The method of claim 13 , wherein the aminoglycoside is amikacin.
16 . The method of claim 13 , wherein the aminoglycoside is tobramicin.
17 . The method of claim 13 , wherein the aminoglycoside is gentamicin.
18 . The method of claim 13 , wherein the lipid based formulation is a liposome.
19 . The method of claim 13 , wherein the pulmonary infection is a pseudomonas, P. aeruginosa, P. paucimobilis, P. putida, P. fluorescens , and P. acidovorans , staphylococcal, Methicillinresistant Staphylococcus aureus (MRSA), streptococcal, Streptococcus pneumoniae, Escherichia coli, Klebsiella, Enterobacter, Serratia, Haemophilus, Yersinia pesos, Burkholderia pseudomallei, B. cepacia, B. gladioli, B. multivorans, B. vietnamiensis, Mycobacterium tuberculosis, M. avium complex (MAC), M. avium, M. intracellulare, M. kansasii, M. xenopi, M. marinum, M. ulcerans, M. fortuitum complex, M. fortuitum , or M. chelonei infection.
20 . The method of claim 13 , wherein the pulmonary infection is caused by cystic fibrosis.
21 . The method of claim 14 , wherein the pulmonary infection is caused by cystic fibrosis.
22 . The method of claim 15 , wherein the pulmonary infection is caused by cystic fibrosis.
23 . The method of claim 16 , wherein the pulmonary infection is caused by cystic fibrosis.
24 . The method of claim 17 , wherein the pulmonary infection is caused by cystic fibrosis.
25 . The method of claim 18 , wherein the pulmonary infection is caused by cystic fibrosis.