Long-acting polymeric delivery systems
View Patent ↗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 delivery system for administration to a subject, the delivery system comprising:
40 wt % to 75 wt % of a polyorthoester;
3 wt % to 25 wt % dimethyl sulfoxide;
10 wt % to 35 wt % triacetin;
2 wt % to 5 wt % bupivacaine; and
0.01 wt % to 1 wt % meloxicam;
wherein the polyorthoester is represented by the structure shown as Formula I:
where
R* is C 1-4 alkyl,
n ranges 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 R 3 is
where x is 2; and
when 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.
2. The delivery system of claim 1 , wherein the delivery system has a viscosity less than 10000 mPa-s when measured at 37° C. using a viscometer.
3. The delivery system of claim 1 , wherein the fraction of A units that are of formula R 1 is about 20 mole percent.
4. The delivery system of claim 1 , wherein the polyorthoester has a weight average molecular weight between 2,500 daltons and 10,000 daltons.
5. The delivery system of claim 1 , wherein the bupivacaine and the meloxicam are solubilized in a single phase.
6. The delivery system of claim 1 , wherein the delivery system is an extended-release composition.
7. The delivery system of claim 1 , further comprising maleic acid.
8. A method for providing analgesia or pain relief to a subject in need thereof, comprising: administering to the subject the delivery system according to claim 1 .
9. The method of claim 8 , wherein the delivery system is administered as a nerve block.
10. The method of claim 8 , wherein the delivery system is administered as a peripheral nerve block.
11. The method of claim 8 , wherein the delivery system is administered to a surgical wound.
12. The method according to claim 8 , wherein the pain is post-operative pain.
13. A method for prophylactic treatment of pain in a subject, comprising: administering to the subject the delivery system according to claim 1 .
14. The delivery system of claim 1 , wherein the polyorthoester comprises the unit