Local Anesthetic Microencapsulation.
Abstract
Local anesthetics have been microencapsulated using a biodegradable ploymer, polylactids. Lidocaine base and hydrochlorides of lidocaine, etidocaine and bupivacaine were coated with various quantities of polymer and the microcapsules sieved into various size ranges. In vitro drug release could be varied from immediate release to 25% in one day. Slower release was achieved with larger microcapsules and higher polymer coatings. Systemic toxicity of selected microcapsules was studied following intraperitoneal injections in mice. Lethal in convulsive doses (LD50 and CD50) were 4.0 to 6.7 times higher with the encapsulated anesthetic hydrochlorides. Peak blood levels in rabbits were significantly lower following I.M. injection of microencapsulated lidocaine and etidocaine than following solution injections. Local toxicity of these microcapsule injections was lower as measure by CPK analysis. The duration of anesthesia was measured by the blockage of th sciatic nerve of the rat (300-450 gm), using etidocaine-HCl microcapsules (150-212 micrometers 47% drug content), 50% in vitro release in 23 hours). Most blocks which lasted 12 hours also lasted 48 hours. The median effective dose for this anesthesia (ED50) is approximately 50 mg (150 mg/kg). The CD50 was 330 mg/kg in this experiment. With etidocaine solutions, 48 hours of anesthesia could not be achieved. One day blockage was achieved, but the dose was above the convulsive dose (ED50>CD50).
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 04, 1983
- Accession Number
- ADA166796
Entities
People
- David E. Creeden
- David L. Williams
- Elie S. Nuwayser
- James H. Kerrigan
- William A. Nucefora