TY - JOUR
T1 - Long-acting poly(DL:lactic acid-castor oil) 3:7-bupivacaine formulation
T2 - Effect of hydrophobic additives
AU - Sokolsky-Papkov, Marina
AU - Golovanevski, Ludmila
AU - Domb, Abraham J.
AU - Weiniger, Carolyn F.
PY - 2011/12
Y1 - 2011/12
N2 - Purpose: To reduce formulation viscosity of bupivacaine/poly(DL lactic acid co castor oil) 3:7 without increasing bupivacaine release rates. Methods: Poly(DL lactic acid) 3:7 was synthesized and bupivacaine formulation prepared by mixing with additives ricinoleic acid or castor oil. In vitro release measurements identified optimum formulation. Anesthetized ICR mice were injected around left sciatic nerve using nerve stimulator with 0.1 mL of formulation. Animals received 10% bupivacaine-polymer formulation with 10% castor oil (p(DLLA:CO)3:7-10% bupi-10% CO) or 15% bupivacaine-polymer with 10% castor oil (p(DLLA:CO)3:7-15% bupi-10% CO). Sensory and motor block were measured. Results: Viscosity of 10% and 15% bupivacaine-p(DLLA:CO)3:7 formulations was reduced using hydrophobic additives; however, castor oil reduced bupivacaine release rates and eliminated burst effect. Less than 10% of the incorporated bupivacaine was released during 6 h, and less than 25% released in 24 h in vitro. In vivo formulation injection resulted in a 24 h motor block and a sensory block lasting at least 72 h. Conclusions: Incorporation of hydrophobic low-viscosity additive reduced viscosity in addition to burst release effects. Bupivacaine-polymer formulation with castor oil additive demonstrated prolonged sensory analgesia in vivo, with reduced duration of motor block.
AB - Purpose: To reduce formulation viscosity of bupivacaine/poly(DL lactic acid co castor oil) 3:7 without increasing bupivacaine release rates. Methods: Poly(DL lactic acid) 3:7 was synthesized and bupivacaine formulation prepared by mixing with additives ricinoleic acid or castor oil. In vitro release measurements identified optimum formulation. Anesthetized ICR mice were injected around left sciatic nerve using nerve stimulator with 0.1 mL of formulation. Animals received 10% bupivacaine-polymer formulation with 10% castor oil (p(DLLA:CO)3:7-10% bupi-10% CO) or 15% bupivacaine-polymer with 10% castor oil (p(DLLA:CO)3:7-15% bupi-10% CO). Sensory and motor block were measured. Results: Viscosity of 10% and 15% bupivacaine-p(DLLA:CO)3:7 formulations was reduced using hydrophobic additives; however, castor oil reduced bupivacaine release rates and eliminated burst effect. Less than 10% of the incorporated bupivacaine was released during 6 h, and less than 25% released in 24 h in vitro. In vivo formulation injection resulted in a 24 h motor block and a sensory block lasting at least 72 h. Conclusions: Incorporation of hydrophobic low-viscosity additive reduced viscosity in addition to burst release effects. Bupivacaine-polymer formulation with castor oil additive demonstrated prolonged sensory analgesia in vivo, with reduced duration of motor block.
KW - bupivacaine-polymer
KW - castor oil
KW - prolonged analgesia
KW - ricinoleic acid
KW - viscosity
UR - http://www.scopus.com/inward/record.url?scp=83555166198&partnerID=8YFLogxK
U2 - 10.1007/s11095-011-0497-3
DO - 10.1007/s11095-011-0497-3
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C2 - 21717256
AN - SCOPUS:83555166198
SN - 0724-8741
VL - 28
SP - 3265
EP - 3273
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 12
ER -