Formulations having increased stability during transition from hydrophobic vehicle to hydrophilic medium
A suspension formulation for therapeutic use includes a non-aqueous, hydrophobic vehicle exhibiting viscous fluid characteristics, a dry particle formulation comprising a biomolecule dispersed in the vehicle, and a surfactant incorporated in at least one of the vehicle and dry particle formulation. A dry particle formulation includes an interferon, a buffer, a surfactant, and one or more stabilizers selected from the group consisting of a carbohydrate, an antioxidant, and an amino acid.
1 . A suspension formulation for therapeutic use, comprising:
a non-aqueous, hydrophobic vehicle exhibiting viscous fluid characteristics;
a dry particle formulation comprising a biomolecule dispersed in the vehicle; and
a surfactant incorporated in at least one of the vehicle and dry particle formulation.
2 . The suspension formulation of claim 1 , wherein the hydrophobic vehicle is non-polymeric.
3 . The suspension formulation of claim 2 , wherein the hydrophobic vehicle comprises substantially sucrose acetate isobutyrate.
4 . The suspension formulation of claim 1 , wherein the biomolecule is an interferon.
5 . The suspension formulation of claim 4 , which delivers the interferon from an implantable drug delivery device at 1 ng/day to 600 ug/day over at least one month.
6 . The suspension formulation of claim 1 , wherein the biomolecule is an interferon omega.
7 . The suspension formulation of claim 1 , wherein the biomolecule is spray dried with the surfactant.
8 . The suspension formulation of claim 1 , wherein the dry particle formulation further comprises one or more stabilizers and a buffer.
9 . The suspension formulation of claim 8 , wherein the stabilizers are selected from the group consisting of carbohydrate, antioxidant, and amino acid.
10 . The suspension formulation of claim 1 , wherein the hydrophobic vehicle is present in an amount greater than 60 wt %.
11 . The suspension formulation of claim 1 , wherein the dry particle formulation is present in a range from 0.01 to 40 wt %.
12 . The suspension formulation of claim 1 , wherein a surfactant loading in the dry particle formulation is in a range from 0 to 10 wt %.
13 . The suspension formulation of claim 1 , wherein a surfactant loading in the vehicle is in a range from 0 to 20 wt %.
14 . A dry particle formulation comprising:
an interferon, a buffer, a surfactant, and one or more stabilizers selected from the group consisting of a carbohydrate, an antioxidant, and an amino acid.
15 . The dry particle formulation of claim 14 , which is spray dried.
16 . The dry particle formulation of claim 14 , wherein the interferon is interferon omega.
17 . (canceled)
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . The dry particle formulation of claim 14 , wherein a concentration of the buffer is in a range from 5 mM to 50 mM.
22 . (canceled)
23 . (canceled)
24 . The dry particle formulation of claim 14 , wherein the interferon is interferon omega, the carbohydrate is sucrose, the antioxidant and/or amino acid is methionine, and the buffer is citrate.
25 . The dry particle formulation of claim 14 , wherein the surfactant is present in a range from 0.01 to 10 wt %.
26 . (canceled)
27 . An implantable delivery device comprising:
a suspension formulation comprising a non-aqueous, hydrophobic vehicle exhibiting viscous fluid characteristics, a dry particle formulation comprising an interferon dispersed in the vehicle, and a surfactant incorporated in at least one of the vehicle and dry particle formulation; and
a reservoir containing the suspension formulation in an amount sufficient to provide continuous delivery of the interferon in a therapeutically effective dose in an environment of use over at least one month.
28 . (canceled)