In Situ Gelling System for Sustained Intraarticular Delivery of Bupivacaine and Ketorolac in Sheep

Eur J Pharm Biopharm. 2022 Mar 29:S0939-6411(22)00060-1. doi: 10.1016/j.ejpb.2022.03.012. Online ahead of print.ABSTRACTSuboptimal control of postoperative pain following knee arthroplasty can slow recovery and reduce patient satisfaction. Intraarticular (IA) administration of bupivacaine and ketorolac offers efficient pain control and minimizes opioid consumption. However, the clinical benefits of this approach are short lived due to rapid clearance of drugs from the joint cavity. Here, we describe a poloxamer based thermoresponsive in situ gelling system for the sustained IA delivery of bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) following knee surgery in an ovine model. Drug loaded formulations were prepared using poloxamer 407, poloxamer 188 and sodium chloride. In vitro characterization was conducted, followed by in vivo evaluation of sustained drug release and safety in an ovine model of knee joint surgery. Rheological studies revealed a Newtonian-like flow of the developed formulation at room temperature, confirming its injectability, followed by a transition to a viscous gel as temperature approached body temperature. The developed formulation successfully sustained the in vivo release of BH for 72 h and KT for 48 h, as determined by circulating drug levels, compared to 24 and 8 h for marketed drug solutions. The concentrations of BH and KT in the synovial fluids at 72 h were 11.5 and 1.8 times that of marketed products, suggesting a significant inc...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Source Type: research