Long-acting polymeric delivery systems
Compositions comprised of a delivery vehicle or delivery system and an active agent dispersed within the delivery vehicle or system, wherein the delivery vehicle or system contains a polyorthoester polymer and a polar aprotic solvent. Also disclosed are low viscosity delivery systems for administration of active agents. The low viscosity delivery systems have a polyorthoester polymer, a polar aprotic solvent and a solvent containing a triglyceride viscosity reducing agent. Compositions described include an amide- or anilide-type local anesthetic of the “caine” classification, and a non-steroidal anti-inflammatory drug (NSAID), along with related methods, e.g., for treatment of post-operative pain or for prophylactic treatment of pain. The compositions are suitable for delivery via, e.g., direct application and instillation, intradermal injection, subcutaneous injection, and nerve block (perineural).
1. A composition, consisting essentially of: a delivery vehicle, bupivacaine, and meloxicam, wherein the ratio of bupivacaine to meloxicam ranges from about 15:1 to 50:1, wherein meloxicam is present in the composition in an amount between about 0.005-0.75 wt % and wherein the composition contains no additional active agents.
2. The composition of claim 1 , wherein bupivacaine is present in the composition in an amount ranging from about 0.1 to 8.0 wt % and meloxicam is present in the composition in an amount ranging from about 0.01-0.5 wt %.
3. The composition of claim 1 , wherein the delivery vehicle is a sustained-release delivery vehicle.
4. The composition of claim 1 , wherein the delivery vehicle is aqueous based.
5. The composition of claim 3 , wherein the sustained-release delivery vehicle is a bioerodible or biodegradable polymer.
6. The composition of claim 5 , wherein the polymer is a polyorthoester represented by the structure shown as Formula I:
where:
R* is a C 1-4 alkyl,
n is an integer ranging from 5 to 400, and
A is a diol, where A is R 1 and/or R 3 , where the fraction of A units that are of formula R 1 is between 0 and 25 mole percent, where
when A is R 3 , R 3 is
where x is 2; and
when A is R 1 , R 1 is
R 5 is H, and R 6 is
the sum of p and q is, on average, 2 and s is 2,
where the resulting component of the polyorthoester comprises the subunit
7. The composition of claim 6 , wherein the delivery vehicle comprises the polyorthoester, a polar aprotic solvent and a triglyceride viscosity reducing agent.
8. The composition of claim 7 , wherein the polar aprotic solvent is selected from dimethyl sulfoxide, N-methyl pyrrolidone and dimethyl acetamide.
9. The composition of claim 7 , wherein bupivacaine is present in the composition at between about 0.01 wt % and about 7.5 wt % of the composition.
10. The composition of claim 9 , wherein meloxicam is present in the composition at between about 0.005 wt % to 0.25 wt % of the composition.
11. The composition of claim 7 , wherein the delivery vehicle comprises:
40 wt % to 75 wt % of the polyorthoester;
5 wt % to 12 wt % dimethyl sulfoxide; and
20 wt % to 40 wt % triacetin;
and wherein bupivacaine is present in an amount of between about 1 wt % to 5 wt %.
12. The composition of claim 11 , wherein the delivery vehicle further comprises 0.01 wt % to 0.3 wt % maleic acid.
13. The composition of claim 1 , wherein meloxicam is present in the composition in an amount ranging from about 0.005-0.25 wt %.
14. The composition of claim 1 , wherein meloxicam is present in the composition in an amount ranging from about 0.005-0.125 wt %.
15. The composition of claim 1 , wherein the ratio of bupivacaine to meloxicam ranges from about 20:1 to 40:1.
16. The composition of claim 1 , wherein the the ratio of bupivacaine to meloxicam ranges from about 30:1 to 35:1.
17. A method for producing analgesia or pain relief in a subject in need thereof, comprising: administering to the subject the composition according to claim 1 .
18. A method for managing pain or for prophylactic treatment of pain in a subject, comprising administering to the subject the composition according to claim 1 .
19. The method of claim 17 , wherein the composition is administered perineural or to a surgical wound.
20. The method of claim 18 , wherein the pain is postsurgical pain.