Pharmaceutical formulation comprising a water-insoluble active agent
View Patent ↗A method of preparing a pharmaceutical formulation comprises providing a solution comprising a first solvent, a second solvent, an active agent, and an excipient. The second solvent is less polar than the first solvent and the excipient is more soluble in water than the active agent. The first and second solvents are removed from the solution to produce particles comprising the active agent and the excipient. In one version, the excipient comprises an amino acid and/or a phospholipid. A pharmaceutical formulation made by a version of the invention comprises particles comprising an active agent and an excipient which at least partially encapsulates the active agent, wherein the excipient is more soluble in water than the active agent.
1. A spray-dried pharmaceutical formulation comprising:
particles comprising an active agent and an excipient encapsulating the active agent, wherein the excipient is more soluble in water than the active agent.
2. A spray-dried pharmaceutical formulation according to claim 1 wherein the particles have a mass median diameter less than 100 μm.
3. A spray-dried pharmaceutical formulation according to claim 1 wherein the particles have a mass median diameter less than 20 μm.
4. A spray-dried pharmaceutical formulation according to claim 1 wherein the particles have a mass median diameter less than 10 μm.
5. A spray-dried pharmaceutical formulation according to claim 1 wherein the particles have a mass median diameter less than 5 μm.
6. A spray-dried pharmaceutical formulation according to claim 1 wherein the excipient comprises a dispersibility enhancing agent.
7. A spray-dried pharmaceutical formulation according to claim 6 wherein the dispersibility enhancing agent comprises one or more of alanine, leucine, trileucine, dipalmitoylphosphatidylcholine, and disteroylphosphatidylcholine.
8. A spray-dried pharmaceutical formulation according to claim 1 wherein at least 20% of the particles have an aerodynamic diameter less than 3.3 μm when determined gravimetrically in an Anderson Cascade Impactor.
9. A spray-dried pharmaceutical formulation according to claim 1 further comprising an additional component at least partially encapsulated in the excipient.
10. A spray-dried pharmaceutical formulation according to claim 9 wherein the additional component comprises a glass forming excipient.
11. A spray-dried pharmaceutical formulation according to claim 10 wherein the glass forming excipient comprises one or more of trileucine, sodium citrate, sodium phosphate, ascorbic acid, polyvinyl pyrrolidone, mannitol, sucrose, trehalose, lactose, proline, and povidone.
12. A pharmaceutical formulation made by a method comprising:
providing a solution comprising a first solvent, a second solvent, an active agent, and an excipient, wherein the second solvent is less polar than the first solvent and wherein the excipient is more soluble in water than the active agent; and
removing the first and second solvents to produce particles comprising the active agent encapsulated by the excipient,
wherein at least 20% of the particles have an aerodynamic diameter less than 3.3 μm when determined gravimetrically in an Anderson Cascade Impactor.
13. A pharmaceutical formulation according to claim 12 wherein the excipient comprises leucine or trileucine.
14. A pharmaceutical formulation according to claim 12 wherein the active agent has a solubility in water less than 1 mg/ml.