Claims
- 1. In a process for the preparation of microcapsules having a particulate core material encapsulated by a polymeric coating wherein the polymer is first dissolved in a solvent in which the core material is not soluble, the polymer is precipitated by phase separation to encapsulate the core material by the addition of a phase separation agent to the polymer-core material-solvent system to form microcapsules of the core material having walls constituted by the polymer, and the microcapsules are thereafter isolated, the improvement which comprises isolating said microcapsules at a temperature at least as low as -30.degree. C.
- 2. The process according to claim 1 wherein the temperature is from about -30.degree. C. to about -70.degree. C.
- 3. The process according to claim 1 wherein the temperature is about -70.degree. C.
- 4. The process according to claim 1 wherein the core material is a solid, injectable drug.
- 5. The process according to claim 4 wherein the drug is equilibrated in a humid environment before being encapsulated.
- 6. The process according to claim 4 wherein the drug is hygroscopic and access of moisture to the drug is restricted before and during encapsulation of the drug.
- 7. The process according to claim 4 wherein the polymer is a bioabsorbable polymer selected from the group consisting of poly (lactic acid) polymers, poly (glycolic acid) polymers, poly (hydroxybutyric acid) polymers and lactide/glycolide copolymers.
- 8. The process according to claim 7 wherein the polymer is a poly (lactic acid) polymer.
- 9. The process according to claim 8 wherein the core material is selected from the group consisting of cyclazocine, tetracycline, ethisterone, digitoxin, antimony potassium tartrate, salmon calcitonin, ACTH, lypressin, sommatostatin, and insulin.
- 10. The process according to claim 8 wherein the solvent is selected from the group consisting of toluene, xylene, benzene, chloroform, cyclohexane, methyl ethyl ketone, ethyl acetate, n-butanol, isopropanol, methanol, acetone, ethanol, tetrachloroethylene and mixtures thereof.
- 11. The process according to claim 1 wherein the phase separation agent is selected from the group consisting of polybutadiene, polybutadiene-methylstyrene copolymers, polyisobutylene, polystyrene, poly (vinyl pyrrolidone), silicone fluids, and poly (methyl vinyl ether and comaleic anhydride half ester) and blends thereof with natural oils.
- 12. The process according to claim 1 wherein said microcapsules are isolated by addition to said system of a nonsolvent for said polymer.
- 13. The process according to claim 12 wherein said nonsolvent for said polymer is relatively volatile and the microcapsules are separated therefrom by volatilization of the nonsolvent.
- 14. The process according to claim 12 wherein said nonsolvent for said polymer is added to said system at a relatively slow rate.
- 15. The process according to claim 12 wherein said nonsolvent for said polymer is selected from the group consisting of alkanes, fluorinated hydrocarbons, hydrogenated naphthalenes and mineral spirits.
- 16. The process according to claim 15 wherein said nonsolvent for said polymer is n-heptane.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional application of application Ser. No. 072,079 filed Sept. 4, 1979, now abandoned, which is a continuation-in-part of our copending, coassigned U.S. patent application Ser. No. 9,875 filed Feb. 7, 1979, now abandoned which is a continuation of application Ser. No. 846,689, filed Oct. 31, 1977, now abandoned which is a continuation of application Ser. No. 648,907, filed Jan. 14, 1976, now abandoned, which is a division of application Ser. No. 566,270, filed Apr. 9, 1975, now abandoned, which is a continuation-in-part of our coassigned U.S. patent application Ser. No. 449,042, filed Mar. 7, 1974, now abandoned.
US Referenced Citations (7)
Divisions (2)
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72079 |
Sep 1979 |
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566270 |
Apr 1975 |
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Continuations (2)
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846689 |
Oct 1977 |
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648907 |
Jan 1976 |
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Continuation in Parts (2)
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9875 |
Feb 1979 |
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449042 |
Mar 1974 |
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