Polyoxaester suspending vehicles for use with implantable delivery systems
View Patent ↗Liquid polyoxaester polymer materials are provided as suspending vehicles suitable for dispensing of pharmaceutically active agents, such as proteins, from delivery devices, for example, pump-driven dosage forms. Polyoxaesters are made from at least one diacid and at least one diol. Through the use of polyoxaesters virtually solvent-free pharmaceutical suspensions can be created.
1. An implantable osmotic dosage form comprising:
a pharmaceutical suspension comprising (i) particles comprising a protein or peptide, and (ii) a suspending vehicle comprising a polyoxaester having a density of about 1.2 g/mL, wherein the pharmaceutical suspension is substantially homogeneous for at least 3 months at 37° C.;
a first wall that maintains its physical and chemical integrity and is substantially impermeable to a pharmaceutical suspension;
a second wall that is partially permeable to an exterior fluid;
an osmotic pump in contact with the first wall and the second wall;
a compartment defined by the first wall and the osmotic pump, wherein the pharmaceutical suspension is positioned within the compartment; and
an exit port in communication with the compartment, wherein the pharmaceutical suspension is flowable through the exit port under a force exerted by the osmotic pump.
2. A method of making the dosage form of claim 1 comprising, loading the pharmaceutical suspension into the compartment.
3. The dosage form of claim 1 , wherein the pharmaceutical suspension is substantially free of solvents.
4. The dosage form of claim 1 , wherein the polyoxaester comprises reaction products of at least one diacid and at least one diol.
5. The dosage form of claim 4 , wherein the diacid is selected from the group consisting of a polyglycolic diacid; a 3,6-trioxaundecanedioic diacid; a 3,6,9-trioxaundecanedioic diacid; and combinations thereof.
6. The dosage form of claim 4 , wherein the diol is selected from the group consisting of an ethyleneglycol, a propanediol, a butanediol, a pentanediol, a cyclopentanediol, a hexanediol, a cyclohexanediol, an octanediol, a decanediol, a dodecanediol, a cyclohexanedimethanol, a polyethyleneglycol, a polypropyleneglycol, and combinations thereof.
7. The dosage form of claim 1 , wherein the polyoxaester comprises condensation products of a mixture comprising a polyglycolic diacid and an ethyleneglycol.
8. The dosage form of claim 7 , wherein the mixture further comprises a 3,6,9-trioxaundecanedioic diacid.
9. The dosage form of claim 7 , wherein the polyoxaester has a molecular weight of from approximately 1,000 to approximately 100,000.
10. The dosage form of claim 1 , wherein the polyoxaester comprises condensation products of a mixture comprising a 3,6,9-trioxaundecanedioic diacid and an ethyleneglycol.
11. The dosage form of claim 10 , wherein the polyoxaester has a molecular weight of from approximately 1,000 to approximately 100,000.
12. The dosage form of claim 1 , wherein the suspending vehicle consists essentially of the polyoxaester.
13. The dosage form of claim 1 , wherein the osmotic pump comprises a piston and a fluid-imbibing agent.
14. The dosage form of claim 1 , wherein the pharmaceutical suspension is substantially homogeneous for at least 6 months.
15. The dosage form of claim 1 , wherein the pharmaceutical suspension is substantially homogeneous for at least 1 year.
16. The dosage form of claim 1 , wherein the pharmaceutical suspension comprises from about 0.1% to about 30% of particles by weight.
17. The dosage form of claim 1 , wherein the pharmaceutical suspension comprises from about 0.5% to about 15% of particles by weight.