TREATMENT OF PAIN ASSOCIATED WITH CESAREAN SECTION SURGERY WITH SUSTAINED-RELEASE LIPOSOMAL ANESTHETIC COMPOSITIONS
In some embodiments provided herein is a method of treating pain associated with cesarean section surgery in a subject, the method comprising administering into the subject a pharmaceutical composition comprising: a) a multivesicular liposome comprising: at least one amphipathic lipid, and at least one neutral lipid; and b) an aqueous phase comprising bupivacaine phosphate, wherein the aqueous phase is encapsulated within the multivesicular liposome.
1 . A method of reducing an amount of a non-opioid analgesic administered to a subject following cesarean section surgery, the method comprising administering into the subject a pharmaceutical composition comprising: a) a multivesicular liposome comprising: at least one amphipathic lipid, and at least one neutral lipid; and b) an aqueous phase comprising bupivacaine phosphate, wherein the aqueous phase is encapsulated within the multivesicular liposome.
2 . A method of reducing an amount of a non-opioid analgesic administered to a subject following cesarean section surgery, the method comprising administering into the subject a pharmaceutical composition comprising multivesicular liposomes encapsulating bupivacaine phosphate, said multivesicular liposomes comprising:
bupivacaine or a salt thereof;
phosphoric acid;
a lipid component comprising at least one amphipathic lipid and at least one neutral lipid lacking a hydrophilic head group; and,
optionally, a cholesterol and/or a plant sterol wherein said multivesicular liposomes are made by a process comprising:
a) preparing a first aqueous component comprising phosphoric acid;
b) preparing a lipid component comprising at least one organic solvent, at least one amphipathic lipid, and at least one neutral lipid lacking a hydrophilic head group;
c) mixing said first aqueous component and said lipid component to form a water-in-oil emulsion, wherein at least one component comprises bupivacaine or a salt thereof;
d) mixing said water-in-oil emulsion with a second aqueous component to form solvent spherules; and
e) removing the organic solvent from the solvent spherules to form multivesicular liposomes encapsulating bupivacaine phosphate.
3 . The method of claim 1 , wherein the aqueous phase further comprises hydrochloric acid.
4 . The method of claim 1 , wherein the amphipathic lipid is selected from the group consisting of phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylglycerols, phosphatidylserines, phosphatidylinositols, phosphatidic acids, cardiolipins, diacyl dimethylammonium propanes, and stearylamines.
5 . The method of claim 1 , wherein the neutral lipid is at least one triglycerides.
6 . The method of claim 1 , wherein the pharmaceutical composition comprises a therapeutically effective amount of bupivacaine phosphate.
7 . The method of claim 1 , wherein the pharmaceutical composition comprises bupivacaine phosphate in an amount equivalent to from about 20 mg to about 300 mg of bupivacaine.
8 . The method of claim 7 , wherein the pharmaceutical composition comprises bupivacaine phosphate in an amount equivalent to from about 133 mg to about 266 mg of bupivacaine.
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10 . The method of claim 1 , wherein the method comprises administering the pharmaceutical composition by transversus abdominis plane (TAP) block.
11 . The method of claim 10 wherein the pharmaceutical composition is administering following completion of the cesarean section surgery.
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14 . The method of claim 1 , wherein the method comprises administering an opioid to the subject following completion of the cesarean section surgery.
15 . The method of claim 14 , wherein the method comprises less than 200 mg of an opioid to the subject following completion of the cesarean section surgery.
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31 . The method of claim 1 , wherein the subject has an AUC for VAS pain intensity scores over the first 72 hours following completion of the cesarean section surgery of from about 100 to about 200.
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34 . The method of claim 1 , wherein the subject has a distress from itchiness score as determined by the OBAS scale of less than 4.
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36 . The method of claim 1 , wherein the plasma concentration of bupivacaine in the subject after about 120 hours following completion of the cesarean section surgery is about 150 ng/mL to about 250 ng/mL, for an amount of the pharmaceutical composition that is equivalent to about 133 mg of bupivacaine.
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53 . The method of claim 31 , wherein the subject has an AUC for VAS pain intensity scores over the first 72 hours following completion of the cesarean section surgery of from about 125 to 175.
54 . The method of claim 31 , wherein the subject has an AUC for VAS pain intensity scores over the first 72 hours following completion of the cesarean section surgery of from about 140 to 160.
55 . The method of claim 34 , wherein the subject has a distress from itchiness score as determined by the OBAS scale of 2.
56 . The method of claim 36 , wherein the plasma concentration of bupivacaine in the subject after about 120 hours following completion of the cesarean section surgery is about 175 ng/mL to about 225 ng/mL.