Ternary non-lamellar lipid compositions
The present invention provides a particulate composition including; a) at least 50% of at least one structure forming amphiphile, b) 0 to 40% of at least one structure swelling amphiphile, and c) 2 to 20% of at least one dispersion stabilizing polymeric amphiphile, where all parts are by weight relative to the sum of the weights of a+b+c and wherein the composition comprises non-lamellar particles or forms non-lamellar particles when contacted with an aqueous fluid. Where component b) is 0% then component a) comprises at least two structure forming amphiphiles. The invention also provides pharmaceutical compositions of the compositions and kits containing the compositions for establishing a pharmaceutical formulation of an active agent.
1. A particulate composition, said composition comprising;
a) at least 50% of at least one structure forming amphiphile comprising at least one lipid component selected from phospholipids, glycolipids, and diglycerides,
b) 2 to 40% of at least one structure swelling amphiphile comprising at least one swelling agent selected from polyoxyethylene alkylethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene castor oil derivatives or polyoxyethylene lipid derivatives, and
c) 2 to 20% of at least one dispersion stabilising polymeric amphiphile comprising at least one polymeric agent selected from poloxamers, PEG-glyceroldioleate, PEG fatty acid esters or PEG-phospholipids,
wherein all parts are by weight relative to the sum of the weights of a+b+c and wherein the composition comprises non-lamellar particles or forms non-lamellar particles when contacted with an aqueous fluid.
2. A composition as claimed in claim 1 wherein the amphiphilic components comprise at least 50% by weight amphiphiles having an aqueous solubility of less than 10 −9 M at 25° C., relative to the total weight of components a+b+c.
3. A composition as claimed in claim 1 wherein the amphiphilic components comprise at least 70%, by weight amphiphiles having an aqueous solubility of less than 10 −9 M at 25° C., relative to the total weight of components a+b+c.
4. A composition as claimed in claim 1 wherein said non-lamellar particles comprise L 3 phase and/or reversed hexagonal phase.
5. A composition as claimed in claim 1 additionally comprising at least one active agent.
6. A composition as claimed in claim 1 wherein component a) comprises a cationic lipid at a level of 1-10% by weight and the composition further comprises at least one nucleic acid active agent.
7. A composition as claimed in claim 1 wherein said non-lamellar particles have a particle size of 10 to 200 μm.
8. A composition as claimed in claim 1 wherein said non-lamellar particles are colloidal.
9. A composition as claimed in claim 8 wherein said non-lamellar particles are stable, both in terms of phase behaviour and particle size, to storage at room temperature for at least 10 days.
10. A composition as claimed in claim 1 which is non-haemolytic up to a concentration of 0.2% total amphiphile.
11. A composition as claimed in claim 1 which is non-haemolytic up to a concentration of 1% total amphiphile.
12. A pharmaceutical formulation comprising at least one composition as claimed in claim 1 and at least one biologically tolerable carrier or excipient.