caa a22 4500 445312637 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0497-3 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0497-3 Long-Acting Poly(DL:Lactic Acid-Castor Oil) 3:7-Bupivacaine Formulation: Effect of Hydrophobic Additives [Elektronische Daten] [Marina Sokolsky-Papkov, Ludmila Golovanevski, Abraham Domb, Carolyn Weiniger] ABSTRACT: 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 0.1mL 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 6h, and less than 25% released in 24h in vitro. In vivo formulation injection resulted in a 24h motor block and a sensory block lasting at least 72h. 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. Springer Science+Business Media, LLC, 2011 bupivacaine-polymer nationallicence castor oil nationallicence prolonged analgesia nationallicence ricinoleic acid nationallicence viscosity nationallicence Sokolsky-Papkov Marina Center for Drug Delivery and Nanomedicine Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Durham Research Center, 985830, 68198-5830, Omaha, Nebraska, USA aut Golovanevski Ludmila Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, POB 12000, Jerusalem, Israel aut Domb Abraham Department of Medicinal Chemistry and Natural Products School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, POB 12000, Jerusalem, Israel aut Weiniger Carolyn Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, POB 12000, Jerusalem, Israel aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3265-3273 0724-8741 28:12<3265 2011 28 11095 https://doi.org/10.1007/s11095-011-0497-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0497-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sokolsky-Papkov Marina Center for Drug Delivery and Nanomedicine Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Durham Research Center, 985830, 68198-5830, Omaha, Nebraska, USA aut NATIONALLICENCE 700 1- Golovanevski Ludmila Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, POB 12000, Jerusalem, Israel aut NATIONALLICENCE 700 1- Domb Abraham Department of Medicinal Chemistry and Natural Products School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, POB 12000, Jerusalem, Israel aut NATIONALLICENCE 700 1- Weiniger Carolyn Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, POB 12000, Jerusalem, Israel aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3265-3273 0724-8741 28:12<3265 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer