Claims for Patent: 11,400,019

Summary for Patent: 11,400,019

Title:	Sustained release drug delivery systems with reduced impurities and related methods
Abstract:	The present disclosure relates to 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 N-oxide of active pharmaceutical agent at a level less than 1 wt %, based on weight of the composition. In some case, a composition comprises metal present at a level less than 5 ppm. Dosage forms and methods are also provided.
Inventor(s):	Miksztal; Andrew R. (Palo Alto, CA), Joice; Judy (San Jose, CA), Autio; Susan (San Jose, CA), Davis; Mark P. (Middleton, WI)
Assignee:	DURECT CORPORATION (Cupertino, CA)
Application Number:	17/504,913
Patent Claims:	1. A pharmaceutical composition comprising: bupivacaine free base present in the pharmaceutical composition in an amount ranging from 10 wt % to 15 wt %, based on weight of the pharmaceutical composition; sucrose acetate isobutyrate present in the pharmaceutical composition in an amount ranging from 63 wt % to 67 wt %, based on weight of the pharmaceutical composition; benzyl alcohol present in the pharmaceutical composition in an amount ranging from 20 wt % to 25 wt %, based on weight of the pharmaceutical composition; benzyl acetate; and 2,6-dimethylaniline, wherein the benzyl acetate is present in the pharmaceutical composition at a level less than 30 mg/mL, wherein the 2,6-dimethylaniline is present in the pharmaceutical composition at a level less than 12 ppm, and wherein the pharmaceutical composition is suitable for parenteral use in humans. 2. The pharmaceutical composition of claim 1, wherein the 2,6-dimethylaniline is present in the pharmaceutical composition at a level less than or equal to 10 ppm. 3. The pharmaceutical composition of claim 1, wherein the 2,6-dimethylaniline is present in the pharmaceutical composition at a level ranging from 0.3 ppm to 10 ppm. 4. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises bupivacaine N-oxide. 5. The pharmaceutical composition of claim 4, wherein the bupivacaine N-oxide is present in the pharmaceutical composition at a level less than 1 wt %, based on weight of the pharmaceutical composition. 6. The pharmaceutical composition of claim 4, wherein the bupivacaine N-oxide is present in the pharmaceutical composition at a level ranging from 0.01 wt % to 1 wt %, based on weight of the pharmaceutical composition. 7. The pharmaceutical composition of claim 1, wherein the benzyl acetate is present in the pharmaceutical composition at a level ranging from 0.1 mg/mL to 20 mg/mL. 8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises benzyl isobutyrate. 9. The pharmaceutical composition of claim 8, wherein the benzyl isobutyrate is present in the pharmaceutical composition at a level ranging from 0.1 mg/mL to 40 mg/mL. 10. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the 2,6-dimethylaniline is present at a level of less than 12 ppm. 11. The pharmaceutical composition of claim 4, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the bupivacaine N-oxide is present at a level of less than 1 wt %, based on weight of the pharmaceutical composition. 12. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the benzyl acetate is present at a level of less than 30 mg/mL. 13. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the benzyl isobutyrate is present at a level of less than 50 mg/mL. 14. A dosage system comprising: a container comprising a first inert material; a closure capable of closing the container, the closure comprising a second inert material; and the pharmaceutical composition of claim 1 contained within the container. 15. The dosage system of claim 14, wherein the second inert material comprises a fluorinated polymer. 16. The dosage system of claim 14, wherein the first inert material comprises glass that does not contain iron. 17. A dosage system comprising: a first container; a second container within the first container, the second container comprising a first inert material and the first container reduces ambient visible light from irradiating onto the second container; and the pharmaceutical composition of claim 1 within the second container. 18. The dosage system of claim 17, wherein the first container comprises a box. 19. A pharmaceutical composition comprising: bupivacaine free base present in the pharmaceutical composition in an amount ranging from 10 wt % to 15 wt %, based on weight of the pharmaceutical composition; sucrose acetate isobutyrate present in the pharmaceutical composition in an amount ranging from 63 wt % to 67 wt %, based on weight of the pharmaceutical composition; benzyl alcohol present in the pharmaceutical composition in an amount ranging from 20 wt % to 25 wt %, based on weight of the pharmaceutical composition; benzyl acetate; and 2,6-dimethylaniline, wherein the benzyl acetate is present in the pharmaceutical composition at a level less than 30 mg/mL, wherein the 2,6-dimethylaniline is present in the pharmaceutical composition at a level less than 12 ppm, and wherein the pharmaceutical composition is sterile. 20. The pharmaceutical composition of claim 19, wherein the 2,6-dimethylaniline is present in the pharmaceutical composition at a level less than or equal to 10 ppm. 21. The pharmaceutical composition of claim 19, wherein the 2,6-dimethylaniline is present in the pharmaceutical composition at a level ranging from 0.3 ppm to 10 ppm. 22. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition further comprises bupivacaine N-oxide. 23. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition further comprises benzyl isobutyrate. 24. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the 2,6-dimethylaniline is present at a level of less than 12 ppm. 25. The pharmaceutical composition of claim 22, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the bupivacaine N-oxide is present at a level of less than 1 wt %, based on weight of the pharmaceutical composition. 26. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the benzyl acetate is present at a level of less than 30 mg/mL. 27. The pharmaceutical composition of claim 23, wherein the pharmaceutical composition is storage stable such that when the pharmaceutical composition is stored in a sealed, upright, clear glass vial at 25.degree. C./60% RH for 36 months, the benzyl isobutyrate is present at a level of less than 50 mg/mL.