Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles
View Patent ↗This invention relates to stable non-aqueous single phase viscous vehicles and to formulations utilizing such vehicles. The formulations comprise at least one beneficial agent uniformly suspended in the vehicle. The formulation is capable of being stored at temperatures ranging from cold to body temperature for long periods of time. The formulations are capable of being uniformly delivered from drug delivery systems at an exit shear rate of between about 1 to 1×10 −7 reciprocal second.
1. An implantable drug delivery device, comprising
a reservoir containing a beneficial agent formulation,
the beneficial agent formulation comprising
a stable non-aqueous single phase biocompatible viscous vehicle, comprising a solvent component and a polymer component, wherein (i) the solvent component is a carboxylic acid ester or lauryl alcohol, (ii) the polymer component is polyvinylpyrrolidone, and (iii) the viscous vehicle has a viscosity of about 10,000 to about 250,000 poise at 37° C., and
particles, comprising a beneficial agent, wherein the particles are uniformly suspended in the vehicle; and
said implantable drug delivery device further comprising an osmotic engine, a piston, and a rate controlling membrane.
2. The device of claim 1 , wherein the vehicle further comprises a surfactant component, wherein the surfactant is glycerol monolaurate or a polysorbate.
3. The device of claim 2 , wherein the vehicle components are in the range of about 5% (w/w) to about 60% (w/w) for solvent, about 5% (w/w) to about 40% (w/w) for surfactant, and about 5% (w/w) to about 60% (w/w) for polymer.
4. The device of claim 1 , wherein the formulation further comprises an antioxidant.
5. The device of claim 4 , wherein the antioxidant is selected from the group consisting of tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, and propyl gallate.
6. The device of claim 1 , wherein the formulation can be delivered from the implantable drug delivery device such that the exit shear rate of the formulation is between about 1 and 1×10 −7 reciprocal second.
7. The device of claim 1 , wherein the formulation is stable at body temperature for extended periods of time.
8. The device of claim 1 , wherein the formulation comprises at least about 0.1% (w/w) beneficial agent.
9. The device of claim 1 , wherein the formulation comprises at least about 10% (w/w) beneficial agent.
10. The device of claim 1 , wherein the formulation is stable at 65° C. for at least about 2 months.
11. The device of claim 1 , wherein the formulation is stable at 37° C. for at least about 3 months.
12. The device of claim 1 , wherein the formulation is stable at 37° C. for at least about one year.
13. The device of claim 1 , wherein the beneficial agent is dried to a low moisture content prior to incorporation in the formulation.
14. The device of claim 1 , wherein the particles are prepared by spray-drying.
15. The device of claim 14 , wherein the particles further comprise a sugar.
16. The device of claim 15 , wherein the sugar is sucrose or mannitol.
17. The device of claim 1 , wherein the carboxylic acid ester is lauryl lactate.
18. The device of claim 1 , wherein during use the implantable device provides a flow rate of the beneficial agent formulation of between 0.3 to 100 ul/day.
19. The device of claim 1 , wherein the vehicle comprises the solvent component and the polymer component in a ratio between 40:60 to 60:40.
20. The device of claim 1 , wherein the formulation further comprises a surfactant.
21. The device of claim 1 , wherein the solvent component is lauryl alcohol.
22. A method of making the implantable drug delivery device of claim 1 , comprising
assembling the reservoir with the osmotic engine, the piston, and the rate controlling membrane,
filling the reservoir with the beneficial agent formulation, and
capping the reservoir with a flow plug.