Method of manufacturing an osmotic delivery device
View Patent ↗A suspension formulation of an insulinotropic peptide (e.g., glucagon-like peptide-1 (GLP-1) or exenatide) is described. The suspension formulation comprises (i) a non-aqueous, single-phase vehicle, comprising one or more polymer and one or more one solvent, wherein the vehicle exhibits viscous fluid characteristics, and (ii) a particle formulation comprising the insulinotropic peptide, wherein the peptide is dispersed in the vehicle. The particle formulation further includes a stabilizing component comprising one or more stabilizers, for example, carbohydrates, antioxidants, amino acids, and buffers. Devices for delivering the suspension formulations and methods of use are also described.
1. A method of manufacturing an osmotic delivery device comprising loading a suspension formulation into a reservoir of the osmotic delivery device,
the suspension formulation comprising:
a particle formulation comprising
an insulinotropic peptide, an antioxidant, and a buffer, wherein the insulinotropic peptide is at least one of exenatide, a derivative of exenatide, and an analogue of exenatide; and
a non-aqueous, single-phase suspension vehicle that comprises about 20 wt % to about 60 wt % solvent and about 80 wt % to about 40 wt % pyrrolidone polymer, the suspension vehicle having a viscosity from 5,000 poise to 50,000 poise at 33° C.;
wherein:
the solvent is at least one of lauryl lactate, lauryl alcohol, and benzyl benzoate;
30 to 90% by weight of the particle formulation is the insulinotropic peptide; the particle formulation has a wt % ratio of insulinotropic peptide to antioxidant of 2.5/1 to 10/1; and the particle formulation is dispersed in the suspension vehicle.
2. The method of claim 1 , wherein the insulinotropic peptide is exenatide.
3. The method of claim 1 , wherein the buffer is selected from at least one of citrate, histidine, succinate, and tris.
4. The method of claim 3 , wherein the buffer is citrate.
5. The method of claim 1 , wherein the antioxidant is methionine.
6. The method of claim 1 , wherein the solvent is benzyl benzoate.
7. The method of claim 1 , wherein the pyrrolidone polymer is polyvinylpyrrolidone.
8. The method of claim 1 , wherein the particle formulation further comprises a carbohydrate.
9. The method of claim 7 , wherein the carbohydrate is at least one of lactose, sucrose, trehalose, cellobiose, and raffinose.
10. The method of claim 9 , wherein the carbohydrate is sucrose.
11. The method of claim 8 , wherein the particle formulation comprises exenatide, sucrose, methionine, and citrate.
12. The method of claim 11 , wherein the particle formulation has a wt % ratio of insulinotropic peptide to antioxidant of 5/1 to 10/1.
13. The method of claim 12 , wherein the solvent is benzyl benzoate.
14. The method of claim 13 , wherein the pyrrolidone polymer is polylvinylpyrrolidone.
15. The method of claim 14 , wherein the particle formulation has a moisture content of less than 5 wt %.
16. The method of claim 15 , wherein particles of the particle formulation have a diameter of about 3 μm to about 50 μm.