title: Long-acting poly(DL:lactic acid-castor oil) 3:7-bupivacaine formulation: effect of hydrophobic additives.
abstract: OBJECTIVE
  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.
authors: Center for Drug Delivery and Nanomedicine Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Durham Research Center, 985830, Omaha, Nebraska 68198-5830, USA.
authors: Marina
authors: M
authors: Sokolsky-Papkov
authors: Ludmila
authors: L
authors: Golovanevski
authors: Abraham J
authors: AJ
authors: Domb
authors: Carolyn F
authors: CF
authors: Weiniger
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002368:Castor Oil / Q000737:chemistry*; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012277:Ricinoleic Acids / Q000737:chemistry*; D012584:Sciatic Nerve / Q000187:drug effects; D012677:Sensation / Q000187:drug effects; D014783:Viscosity
chemical_list: D000779:Anesthetics, Local; D012277:Ricinoleic Acids; D019344:Lactic Acid; D002368:Castor Oil; C030521:ricinoleic acid; D002045:Bupivacaine