FORMULATION OF SUSTAINED RELEASE BUPIVACAINE HCL INJECTION IN REVERSE MICELLE SYSTEM

• Main Author: Aryani Arvin, Yang
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78943
• Institution: Institut Teknologi Bandung

Bupivacaine is a local anesthetic from amide group, which has short onset time and long acting duration with serious cardiotoxicity as a systemic side effect. Controlling bupivacaine release from the dosage form is suggested to slow systemic absorption then minimizing the adverse effect. One strategy to do so is by encapsulating bupivacaine HCI in particular carrier system. The aim of this research was developing reverse micelle as a nanocarrier system for bupivacaine HCI to sustain its release. Reverse micelles (water in oil nanoemulsion) were formed spontaneously with emulsification method. Castor oil was used as a dispersing medium, Tween 20 as a surfactant, and PEG 400 as cosurfactant. Bupivacaine HCI as a hydrophilic active ingredient wa%dissolved in aqueous phase. Funher, set of evaluations were perfomed to ensure the qualities of the preparation, including particle morphology using cyro TEM, viscosity, entrapment efficiency, loading capacity, accelerated stability test, in vitro release study, and in vivo activity in animal model. Using fixed ratio of surfactant, cosurfactant, aqueaous, and castor oil, bupivacaine HCl-loaded reverse micelles were successfully formed. Reverse micelle containing bupivacaine HCI has sphrerical shape with average particle size of 171.2±17.65 nm. Bupivacaine HCl-loaded reverse micelle showed viscosity of 68.74±2.26 mPa•s; high entrapment efficiency of 97.9±0.94%; and loading capacity of 14.7±0.09 mg/mL micelle. Under stress condition during 3 months observation, the micelle containing bupivacaine HCI was stable both physically and chemically. The release profile of bupivacaine HCI from the micelle showed sustained pattern with release rate of after 24 hours observation. While, with the same study the bupivacaine HCI aqueous solution exhibited immediate release. This data was confiniled by the local anesthetic effect in vivo, in which bupivacaine micelle exhibited slow and sustained action as compared to conventional preparation. The local anesthesia effect of bupivacaine HCI micelle appeared 1.5 hours after subcutaneous administration and lasted until 24 hours. While, faster anesthetic effect was generated by bupivacaine HCI solution i.e 0.5 hours after administration but working shorter of only 3 hours. Taken together, bupivacaine HCI encapsulated in the reverse micelle is able to sustain the local anesthetic effect by controlling the release after subcutaneous injection.