Osmotic delivery systems and piston assemblies for use therein
An osmotic delivery system is disclosed for delivering an active agent formulation to a fluid environment. The osmotic delivery system typically comprises a reservoir having a lumen that contains the active agent formulation and an osmotic agent formulation and a piston assembly positioned in the lumen to isolate the active agent formulation from the osmotic agent formulation. The piston assembly typically comprises a body constructed and arranged for positioning in the lumen. The body is typically made of a polymeric material that is, for example, resistant to leaching in an organic solvent. In one embodiment, the body is a columnar body having a rim at a distal end thereof for engaging and sealing against a wall of the reservoir and the piston assembly further comprises a spring retained at the distal end of the columnar body for biasing the rim of the columnar body against the wall of the reservoir.
1. A method of treating diabetes in a subject in need of such treatment, comprising administering an osmotic delivery system loaded with a suspension formulation comprising an active agent to the subject, wherein the osmotic delivery system comprises:
a reservoir comprising an interior wall defining a lumen that contains the suspension formulation and an osmotic agent formulation;
a piston assembly positioned in the lumen to isolate the suspension formulation from the osmotic agent formulation, wherein the piston assembly comprises:
a columnar body that has a core made of a polymeric material comprising an ultra-high molecular weight polyethylene,
a rim at a distal end thereof for engaging and sealing against the interior wall of the reservoir, and
a spring retained at the distal end for biasing the rim against the wall of the reservoir;
the suspension formulation comprises a suspension vehicle comprising one or more organic solvents selected from the group consisting of benzyl benzoate and benzyl alcohol;
the suspension formulation comprises less than 9.0 μg/mL of non-volatile leachates produced by the piston assembly and resulting from an interaction between the suspension formulation and the piston assembly; and
the active agent is exendin-4.
2. The method of claim 1 , wherein the spring is retained in a cavity at the distal end of the columnar body.
3. The method of claim 1 , wherein the spring is made of a non-reactive metal.
4. The method of claim 1 , the osmotic delivery system further comprising a semipermeable membrane positioned at a first end of the reservoir adjacent the osmotic agent formulation.
5. The method of claim 4 , the osmotic delivery system further comprising a flow modulator positioned at a second end of the reservoir adjacent the suspension formulation, said flow modulator having an orifice for delivering the suspension formulation to the fluid environment.
6. The method of claim 1 , wherein the piston assembly is movable within the reservoir in response to pressure within the reservoir.
7. The method of claim 1 , wherein the reservoir is made of an impermeable material.
8. The method of claim 1 , wherein the suspension formulation comprises a particle formulation of the active agent.
9. The method of claim 1 , wherein:
the reservoir is made of a titanium alloy;
the suspension formulation comprises
a particle formulation of the active agent, the particle formulation comprising exendin-4 and further comprising sucrose, methionine, citric acid monohydrate, and sodium citrate, and
the suspension vehicle comprising benzyl benzoate and further comprising polyvinylpyrrolidone;
the osmotic agent formulation comprises two cylindrical tablets, each tablet comprising sodium chloride salt with cellulosic and povidone binders;
the spring retained at the distal end for biasing the rim against the wall of the reservoir is a canted coil spring;
the osmotic delivery system further comprising:
a semipermeable membrane positioned at a first distal end of the reservoir adjacent the osmotic agent formulation, wherein the semipermeable membrane comprises polyurethane; and
a flow modulator positioned at a second distal end of the reservoir adjacent the suspension formulation, wherein the flow modulator comprises polyetheretherketone.
10. The method of claim 1 , wherein the suspension formulation comprises less than 1.4 μg/mL of volatile leachates produced by the piston assembly and resulting from an interaction between the suspension formulation and the piston assembly.
11. The method of claim 1 , wherein the suspension vehicle comprises benzyl benzoate.
12. The method of claim 1 , wherein the suspension vehicle comprises benzyl alcohol.