Sustained release drug delivery systems and related methods

Patent metadata

Field	Value
Publication number	US-12433877-B2
Application number	US-202217744509-A
Country	US
Kind code	B2
Filing date	May 13, 2022
Priority date	Jan 12, 2021
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

The present disclosure provides for methods of producing analgesia in a subject. In some cases, methods produce analgesia in a subject undergoing arthroscopic subacromial decompression surgery. The present disclosure also relates to improved sustained release drug delivery systems. In some cases, a composition comprises an active pharmaceutical agent; at least one of sucrose acetate isobutyrate and a polyorthoester; an organic solvent; and 2,6-dimethylaniline, wherein the 2,6-dimethylaniline is present at a level less than 500 ppm. In some cases, a composition comprises bupivacaine N-oxide at a level less than 1 wt %, based on weight of the composition. In some cases, a composition comprises metal present at a level less than 5 ppm. Dosage forms and methods are also provided.

First claim

What is claimed is:

1. A method of producing post-surgical analgesia in a subject having arthroscopic subacromial decompression surgery, comprising:
drawing up 5 mL of a bupivacaine composition into a 5 mL syringe using a 16-gauge or larger bore needle to fill the 5 mL syringe, the bupivacaine composition comprising:
bupivacaine free base or salt thereof present in an amount ranging from 10 wt % to 15 wt %, based on weight of the bupivacaine composition,
sucrose acetate isobutyrate present in an amount ranging from 63 wt % to 67 wt %, based on weight of the bupivacaine composition, and
benzyl alcohol present in an amount ranging from 20 wt % to 25 wt %, based on weight of the bupivacaine composition;

discarding the 16-gauge or larger bore needle; and
administering the 5 mL of the bupivacaine composition into the subacromial space of the subject using an 18-gauge or larger bore needle to produce post-surgical analgesia,
wherein the method comprises arthroscopically visualizing the subacromial space to confirm placement of the 18-gauge or larger bore needle in the subacromial space prior to administering the bupivacaine composition.

2. The method of claim 1 , further comprising storing the bupivacaine composition at a temperature ranging from 15° C. to 30° C. prior to the drawing up.

3. The method of claim 1 , wherein the bupivacaine composition is stored in a clear, glass vial prior to the drawing up.

4. The method of claim 1 , wherein the bupivacaine composition is stored in a 5 mL single-dose vial prior to the drawing up.

5. The method of claim 1 , wherein the bupivacaine composition is stored in a vial packaged in a carton prior to the drawing up.

6. The method of claim 5 , wherein ten of the vials are packaged in the carton, which is a 10-unit carton.

7. The method of claim 5 , wherein the carton is stored in a box.

8. The method of claim 5 , wherein the carton protects the bupivacaine composition from light.

9. The method of claim 1 , wherein the bupivacaine free base or salt thereof comprises bupivacaine free base.

10. The method of claim 1 , wherein the bupivacaine composition comprises from 125 mg/mL to 150 mg/mL of bupivacaine free base equivalent.

11. The method of claim 1 , wherein the bupivacaine composition comprises 132 mg/mL of bupivacaine free base equivalent.

12. The method of claim 1 , wherein the bupivacaine composition comprises from 600 mg to 700 mg of bupivacaine free base equivalent.

13. The method of claim 1 , wherein the bupivacaine composition comprises 660 mg of bupivacaine free base equivalent.

14. The method of claim 1 , wherein the bupivacaine free base or salt thereof is present in the bupivacaine composition in an amount of about 12 wt %, based on weight of the bupivacaine composition.

15. The method of claim 1 , wherein the benzyl alcohol is present in the bupivacaine composition in an amount of about 22 wt %, based on weight of the bupivacaine composition.

16. The method of claim 1 , wherein the sucrose acetate isobutyrate is present in the bupivacaine composition in an amount of about 66 wt %, based on weight of the bupivacaine composition.

17. The method of claim 1 , wherein the administering comprises inserting the 18-gauge or larger bore needle into the subject through an arthroscopic port or through intact skin to reach the subacromial space of the subject.

18. The method of claim 1 , wherein the method provides a bupivacaine maximum plasma concentration (Cmax) of not more than 2850 ng/mL.

19. The method of claim 1 , wherein the method provides a mean bupivacaine maximum plasma concentration (Cmax) ranging from 200 ng/ml to 1500 ng/mL.

20. The method of claim 1 , wherein the method comprises administering the 5 mL of the bupivacaine composition in a single dose and then not administering additional bupivacaine within 168 hours after the single dose and not administering any other local anesthetic within 168 hours after the single dose.

Assignees

• Durect Corp

Inventors

• Verity Adrian Neil
• Halladay Steven
• Miller Vaeling
• Langecker Peter
• Lissin Dmitri
• Miksztal Andrew R
• Joice Judy
• Autio Susan
• Davis Mark P

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P23/02

  Local anaesthetics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P23/00 Primary

  Anaesthetics · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title