Compositions and methods for delivering pharmaceutical agents
View Patent ↗Provided herein are compositions and methods for treating respiratory and pulmonary vascular disease. In particular, provided herein are spray dried simvastatin for delivery to the lung.
1. A composition comprising a simvastatin (Sim) particle, wherein said particle is a dry powder, wherein said Sim particle has a mass median aerodynamic diameter (MMAD) of 7.38±0.2 μm, a Fine Particle Fraction (FPF) of 18.40±3.16%, and an emitted dose (ED) of 84.33±4.79%, and wherein said particle is made by a method, comprising:
a) preparing a first solution comprising said Sim in methanol; and
b) spraying said first solution using a spray drying apparatus;
and wherein said composition is suitable for delivery by inhalation.
2. A composition comprising a simvastatin (Sim) and L-carnitine (L-Car) or Sim and D-mannitol (Man) particle, wherein said particle is a dry powder, wherein said Sim and L-Car particle has a MMAD of 19.55±2.52 μm, a FPF of 6.57±1.04%, and an ED of 93.65±5.53% and said Sim and Man particle has MMAD of 6.31±0.19, 9.86±1.13, 15.46±3.17, 7.29±1.04, or 13.28±0.84 μm, a FPF of 26.07±4.245, 9.15±1.55, 6.56±0.86, 17.57±3.36, or 10.40±3.16%, and an emitted dose ED of 100, 76.77±3.36, 70.93±10.09, or 89.84±5.52%, and wherein said particle is made by a method, comprising:
a) preparing a first solution comprising said Sim in methanol and a second solution comprising L-Car or Man in methanol;
b) mixing said first and second solutions to generate a mixture; and
c) spraying said mixture using a spray drying apparatus;
and wherein said composition is suitable for delivery by inhalation.
3. The composition of claim 2 , wherein said-Sim and Man are present at a molar ratio of 90:10 to 10:90 Sim:Man.
4. The composition of claim 2 , wherein said Sim and L-Car are present at a molar ratio of 90:10 to 10:90 Sim:L-Car.
5. A method of treating a lung disorder in a subject, comprising: administering the composition of claim 1 to a subject diagnosed with or having signs or symptoms of said lung disorder under conditions such that said signs or symptoms are reduced.
6. The method of claim 5 , wherein said lung disorder is selected from the group consisting of pulmonary hypertension (PH), COPD, asthma, acute lung injury, and radiation induced lung injury.
7. The method of claim 5 , further comprising administering an additional treatment for a lung disorder.
8. The method of claim 7 , wherein said additional treatment is selected from the group consisting of a vasodilator, an anticoagulant, an antiplatelet agent, an anti-inflammatory agent, and a vascular-remodeling therapy.
9. The method of claim 5 , wherein said composition is administered to the lung of said subject using a dry powder inhaler.