Article of manufacture comprising local anesthetic, buffer, and glycosaminoglycan in syringe with improved stability

An article of manufacture comprising a terminally-sterilized aqueous liquid composition including:

• (a) an anionic polysaccharide, selected from the group consisting of:
• hyaluronic acid, chondroitin sulfate, pentosan polysulfate, dermatan sulfate, heparin, heparan sulfate, and keratan sulfate;
• (b) a local anesthetic, wherein the local anesthetic is selected from the group consisting of bupivacaine, mepivacaine, prilocaine, ropivacaine, dibucaine and a combination thereof;
• and
• (c) a buffer selected from the group consisting of phosphate buffer, bicarbonate buffer, Tris (Tris(hydroxymethyl)aminomethane) buffer, MOPS buffer (3-(N-morpholino)propanesulfonic acid), HEPES (N-(2-hydroxyethyl)piperazine-N-(2-ethanesulfonic acid) buffer, ACES (2-[(2-amino-2-oxoethyl)amino]ethanesulfonic acid) buffer, ADA (N-(2-acetamido)2-iminodiacetic acid) buffer, AMPSO (3-[(1,1-dimethyl-2-hydroxyethyl)amino]-2-propanesulfonic acid) buffer, BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid buffer, Bicine (N,N-bis(2-hydroxyethylglycine) buffer, Bis-Tris (bis-(2-hydroxyethyl)imino-tris(hydroxymethyl)methane buffer, CAPS (3-(cyclohexylamino)-1-propanesulfonic acid) buffer, CAPSO (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid) buffer, CHES (2-(N-cyclohexylamino)ethanesulfonic acid) buffer, DIPSO (3-[N,N-bis(2-hydroxyethyl)amino]-2-hydroxy-propanesulfonic acid) buffer, HEPPS (N-(2-hydroxyethylpiperazine)-N′-(3-propanesulfonic acid) buffer, HEPPSO (N-(2-hydroxyethyl)piperazine-N′-(2-hydroxypropanesulfonic acid) buffer, MES (2-(N-morpholino)ethanesulfonic acid) buffer, triethanolamine buffer, imidazole buffer, glycine buffer, ethanolamine buffer, MOPSO (3-(N-morpholino)-2-hydroxypropanesulfonic acid) buffer, PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid) buffer, POPSO (piperazine-N,N′-bis(2-hydroxypropaneulfonic acid) buffer, 2TAPS (N-tris[hydroxymethyl)methyl-3-aminopropanesulfonic acid) buffer, TAPSO (3-[N-tris(hydroxymethyl)methylamino]-2-hydroxy-propanesulfonic acid) buffer, TES (N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid) buffer, tricine (N-tris(hydroxymethyl)methylglycine buffer), 2-amino-2-methyl-1,3-propanediol buffer, and 2-amino-2-methyl-1-propanol buffer, and a combination thereof, wherein the components of (a), (b), and (c) form a composition;
• and
• (d) a container comprising a syringe or vial that is compatible with sterilization by heat, wherein the container packages the composition formed by the components of (a), (b), and (c), wherein the container is constructed of a plastic selected from the group consisting of cyclic olefin polymer plastic, and cyclic olefin copolymer plastic;
• wherein the pH of the aqueous liquid composition is between 6.8 and 8.2, and wherein stability of the local anesthetic, when tested after the sterilization by heat and after 12 months of storage, results in a content of local anesthetic in the aqueous solution that is at least 95% of the local anesthetic originally present in the aqueous liquid composition.