Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485705 | Journal of Pharmaceutical Sciences | 2010 | 7 Pages |
Abstract
Prolonged analgesia may be achieved using a single injection of slow-release local anesthetic formulation. The study objective was to improve the efficacy of a previously reported formulation comprising 10% bupivacaine in poly(dl:lactic acid co castor oil) 3:7. The polymer was loaded with 15% bupivacaine and injected through a 22G needle close to the sciatic nerve of ICR mice. Sensory and motor nerve blockade were measured. The efficacy and toxicity of the polymer-drug combination were determined. Sixty percent of the incorporated bupivacaine was released during 1Â week in vitro. During in vitro release no burst effect was seen, suggesting low toxicity of the formulation. Single injection of 0.1Â mL of 15% polymer-bupivacaine formulation caused motor block that lasted 64Â h and sensory block that lasted 96Â h. The MTD of the polymer-drug formulation was established as 0.175Â mL. Microscopic examination of the injection sites revealed reversible nerve inflammation and normal internal organs. The polymer poly(dl:lactic acid co castor oil) 3:7 is a safe carrier for prolonged activity of bupivacaine up to 96Â h. The increase of drug load in the formulation reduces the drug release rates due to stronger polymer-drug interactions and higher overall hydrophobicity of the formulation
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Authors
Marina Sokolsky-Papkov, Ludmila Golovanevski, Abraham J. Domb, Carolyn F. Weiniger,