Dual action, inhaled formulations providing both an immediate and sustained release profile
Methods for formulating immediate and sustained release anti-infectives and delivery of such for treatment of respiratory tract infections and other medical conditions, and devices and formulations used in connection with such are described.
1. An aerosolized composition of particles, comprising:
free, unencapsulated ciprofloxacin;
a pharmaceutically acceptable excipient; and
liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar and comprised of hydrogenated soy phosphatidyl-choline (HSPC) and cholesterol;
wherein the composition is formulated for aerosolized delivery;
further wherein particles of the aerosol have a diameter in a range from about 2microns to about 4 microns and the free ciprofloxacin comprises 5% or more of a total of both free ciprofloxacin and liposome-encapsulated ciprofloxacin in the formulation.
2. The aerosolized composition of claim 1 , further comprising:
an additional pharmaceutically active drug chosen from a bronchodilator and an anti-inflammatory drug.
3. The aerosolized composition of claim 2 , wherein the additional pharmaceutically active drug is a bronchodilator chosen from β-adrenergic receptor agonists, antimuscarinics and combinations thereof.
4. The aerosolized composition of claim 2 , wherein the additional pharmaceutically active drug is an antiinflammatory selected from the group consisting of a corticosteroid, a leukotriene receptor antagonist, a leukotriene synthesis inhibitor, and a cyclooxygenase inhibitor.
5. The aerosolized composition of claim 1 , wherein the free ciprofloxacin comprises between about 5% and about 75% of the total of both the free ciprofloxacin and liposome-encapsulated ciprofloxacin; and
wherein release of the total available amount of encapsulated ciprofloxacin occurs between about 2 hours and about 150 hours.
6. The aerosolized composition of claim 1 , wherein the aerosolized composition is comprised of the ciprofloxacin in an amount of between 0.01% to 40% by weight.
7. The aerosolized composition of claim 1 , wherein the liposome-encapsulated ciprofloxacin is released at a rate of between about 0.1% to 100% per hour with substantially complete release of antibiotic occurring after about 1 to 24 hours.
8. The aerosolized composition of claim 1 , wherein the liposome-encapsulated ciprofloxacin is released at a rate of between about 0.5% to 20% per hour with substantially complete release of antibiotic occurring after about 1 to 12 hours.
9. The aerosolized composition of claim 1 , wherein the liposome-encapsulated ciprofloxacin is released at a rate of between about 2% to 10% per hour with substantially complete release of antibiotic occurring after about 1 to 6 hours.
10. An aerosolized composition of particles, comprising:
free, unencapsulated ciprofloxacin;
a pharmaceutically acceptable excipient; and
liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar and comprised of hydrogenated soy phosphatidyl-choline (HSPC) and cholesterol;
wherein the composition is formulated for aerosolized delivery;
further wherein particles of the aerosol have a diameter in a range from about 2microns to about 4 microns;
wherein the free ciprofloxacin comprises between about 5% and about 75% of the total of both the free ciprofloxacin and liposome-encapsulated ciprofloxacin; and
wherein the liposome encapsulated ciprofloxacin is released at a rate of between about 2% to 10% per hour with substantially complete release of ciprofloxacin occurring after about 1 to 6 hours.