Preparation of injectable suspensions having improved injectability
View Patent ↗Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.
1. A method for preparing a composition suitable for injection through a needle into a host, comprising:
(a) mixing dry microparticles with an injection vehicle to form a first suspension, wherein the microparticles comprise a polymeric binder and wherein the microparticles are suspended in the injection vehicle at a concentration of from about 175 mg/ml to about 400 mg/ml; and
(b) mixing the first suspension with a viscosity enhancing agent to form a second suspension, wherein the viscosity enhancing agent increases viscosity of a fluid phase of the second suspension to be in the range of from about 20 cp to about 600 cp at 20° C., wherein the viscosity of the fluid phase of the second suspension provides injectability of the composition into the host through a needle ranging in diameter from 18-22 gauge.
2. The method of claim 1 , wherein the viscosity of the fluid phase of the second suspension after step (b) is from about 200 cp to about 600 cp at 20° C.
3. The method of claim 1 , wherein the concentration of microparticles in the first suspension is greater than about 300 mg/ml and less than about 400 mg/ml.
4. The method of claim 1 , wherein a viscosity of the viscosity enhancing agent is from about 1000 to about 2000 cp at 20° C.
5. The method of claim 1 , wherein the viscosity enhancing agent comprises sodium carboxymethyl cellulose.
6. The method of claim 1 , wherein a volume of the viscosity enhancing agent mixed with the first suspension is approximately 10-25% of the volume of the first suspension.
7. The method of claim 1 , further comprising before step (b):
(c) withdrawing the first suspension into a first syringe.
8. The method of claim 7 , wherein step (b) comprises:
(i) providing a second syringe containing the viscosity enhancing agent;
(ii) coupling the first syringe to the second syringe so that fluid can pass between the first and second syringes; and
(iii) repeatedly passing the first suspension and the viscosity enhancing agent between the first and second syringes.
9. A method for administering a composition to a host, comprising:
(a) mixing dry microparticles with an injection vehicle to form a first suspension, wherein the microparticles comprise a polymeric binder and wherein the microparticles are suspended in the injection vehicle at a concentration of from about 175 mg/ml to about 400 mg/ml;
(b) mixing the first suspension with a viscosity enhancing agent to form a second suspension, wherein the viscosity enhancing agent increases viscosity of a fluid phase of the second suspension to be in the range of from about 20 cp to about 600 cp at 20° C. wherein the viscosity of the fluid phase of the second suspension provides injectability of the composition into the host; and
(c) injecting the second suspension into the host through a needle ranging in diameter from 18-22 gauge.
10. A method for administering a composition to a host, comprising:
(a) mixing dry microparticles with an injection vehicle to form a suspension, wherein the injection vehicle has a viscosity at 20° C. of less than about 60 cp, wherein the microparticles comprise a polymeric binder and wherein the microparticles are suspended in the injection vehicle at a concentration of from about 175 mg/ml to about 400 mg/ml;
(b) changing the viscosity of a fluid phase of the suspension to be in the range of from about 20 cp to about 600 cp at 20° C. wherein the viscosity of the fluid phase of the second suspension provides injectability of the composition into the host;
(c) withdrawing the suspension into a syringe; and
(d) injecting the suspension from the syringe into the host through a needle ranging in diameter from 18-22 gauge.
11. The method of claim 10 , wherein step (b) comprises:
changing the temperature of the fluid phase of the suspension.
12. The method of claim 10 , wherein step (c) is performed prior to step (b), and step (b) comprises:
adding a viscosity enhancing agent to the suspension in the syringe to thereby increase the viscosity of the fluid phase of the suspension.
13. The method of claim 12 , wherein the viscosity enhancing agent comprises sodium carboxymethyl cellulose.
14. The method of claim 9 , wherein the microparticles comprise an active agent.
15. A method of making a composition suitable for injection through a needle into a host, comprising:
(a) providing microparticles comprising a polymeric binder;
(b) providing an injection vehicle having a viscosity of at least 20 cp at 20° C.; and
(c) suspending the microparticles in the injection vehicle to form a suspension, wherein the microparticles are suspended in the injection vehicle at a concentration of from about 175 mg/ml to about 400 mg/ml, wherein the viscosity of a fluid phase of the suspension is in the range of from about 20 cp to about 600 cp at 20° C., wherein the viscosity of the fluid phase of the suspension provides injectability of the composition into the host through a needle ranging in diameter from 18-22 gauge.
16. The method of claim 10 , wherein step (c) is performed prior to step (b).
17. A method for preparing a composition suitable for injection through a needle into a host, comprising:
(a) mixing dry microparticles with an injection vehicle to form a first suspension, wherein the microparticles comprise a polymeric binder and wherein the microparticles are suspended in the injection vehicle at a concentration of from about 175 mg/ml to about 400 mg/ml; and
(b) mixing the first suspension with a viscosity enhancing agent to form a second suspension, wherein the viscosity enhancing agent increases viscosity of a fluid phase of the second suspension to be in the range of from about 20 cp to about 600 cp at 20° C., wherein the viscosity of the fluid phase of the second suspension provides injectability of the composition into the host through a needle of medically acceptable size.
18. The method of claim 17 , wherein an internal diameter of the needle ranges from about 700 to about 400 microns.
19. A method of making a composition suitable for injection through a needle into a host, comprising:
suspending microparticles comprising a polymeric binder in an injection vehicle having a viscosity of at least 20 cp at 20° C. to form a suspension, wherein the microparticles are suspended in the injection vehicle at a concentration of from about 175 mg/ml to about 400 mg/ml, wherein the viscosity of a fluid phase of the suspension is in the range of from about 20 cp to about 600 cp at 20° C., wherein the viscosity of the fluid phase of the suspension provides injectability of the composition into the host through a needle of medically acceptable size.
20. The method of claim 19 , wherein an internal diameter of the needle ranges from about 700 to about 400 microns.