SUSTAINED RELEASE BIODEGRADABLE INTRACANALICULAR INSERTS COMPRISING A HYDROGEL AND AN ACTIVE AGENT
Provided herein are sustained release biodegradable intracanalicular inserts comprising a hydrogel and an active agent, methods of treating or preventing an ocular disease in a subject in need thereof by administering such inserts as well as methods of manufacturing such inserts.
1 . A sustained release biodegradable intracanalicular insert comprising a hydrogel and an active agent, wherein the active agent is in the form of particles, wherein the hydrogel comprises a polymer network comprising polyethylene glycol units having an average molecular weight in the range of from about 2.000 to about 100,000 Daltons, wherein the polymer network comprises multi-arm polymer units comprising 4-8 polyethylene glycol units and cross-linking units comprising an amine and wherein the active agent particles are dispersed within the hydrogel.
2 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the active agent particles have a d50 value of less than about 50 μm.
3 . The sustained release biodegradable intracanalicular insert of claim 2 , wherein the active agent particles have a d50 value ranging from 3 to 17 μm.
4 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the active agent is a low solubility active agent.
5 .- 14 . (canceled)
15 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert in a dried state contains from about 15% to about 80% by weight of the active agent based on the total weight of the insert and from about 20% to about 60% by weight polymer units based on the total weight of the insert.
16 . (canceled)
17 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert in a dried state contains from 45% to 55% by weight of the active agent based on the total weight of the insert.
18 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert contains a surfactant.
19 . (canceled)
20 . The sustained release biodegradable intracanalicular insert of claim 18 , wherein the insert in a dried state contains from about 0.01% to about 5% by weight of a surfactant based on the total weight of the insert.
21 . The sustained release biodegradable intracanalicular insert of, wherein the insert contains a non-ionic surfactant.
22 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the active agent content as measured by HPLC after at least 3 months of storage at a temperature of from 2 to 8° C. is from about 90 to about 110% by weight.
23 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the amount of impurities as measured by HPLC after at least 3 months of storage at a temperature of from 2 to 8° C. is not more than 3.0%.
24 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert is in the form of a fiber.
25 .- 26 . (canceled)
27 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert disintegrates in the canaliculus within about 1 to about 6 months after insertion.
28 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert after insertion to the canaliculus releases a therapeutically effective amount of active agent over a period of at least about 1 month after insertion.
29 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the active agent is released from the insert after insertion to a human subject at an average rate of about 0.1 μg/day to about 10 μg/day.
30 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the tear fluid concentration of active agent after insertion to a human subject ranges from about 0.1 μg/mL to about 10 μg/mL.
31 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the insert disintegrates in the canaliculus prior to complete solubilization of the active agent particles contained in the insert.
32 . The sustained release biodegradable intracanalicular insert of claim 1 , wherein the fiber has been stretched prior to or after drying.
33 . (canceled)
34 . The sustained release biodegradable intracanalicular insert of claim 32 , wherein the fiber has been stretched by a stretch factor in the longitudinal direction of from about 1.0 to about 4.0.
35 .- 51 . (canceled)