Abstract
Purpose. Methods of delaying the action of local anesthetics are important, since short duration of action limits their use in the treatment of postoperative and chronic pain. The present study evaluated the use of low-viscosity gels in prolonging the release of lidocaine.
Methods. Release of lidocaine from 2% lidocaine-HC1 containing methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), sodiumcarboxymethyl cellulose (CMC), and poloxamer 407 (PO) gels was studied in phosphate buffer, pH 7.4, at 37°C. Commercial metylcellulose gel (MCcom) served as control. The in vivo efficacy of the respective gel formulations were evaluated in rats. The gel was injected into the vicinity of the sciatic nerve and nociception and motor function were tested.
Results. The cumulative amount of lidocaine released during 8 hr was slowest from the PO gel, followed by the CMC, HPMC and MC gels. The antinociceptive effect was not prevented by the motor block and lasted longest with the PO gel. Good linear and rank order correlation was obtained between in vitro and in vivoresults. The microscopic examination of the tissue samples revealed only mild or no irritation of the skeletal muscle tissue by the PO, HPMC, and CMC gels.
Conclusions. Based on these results poloxamer gel proved to be the most promising carrier for lidocaine.
This is a preview of subscription content, access via your institution.
REFERENCES
B.R. Fink, G. Asheim, S.J. Kish, and T.S. Croley. Neurokinetics of lidocaine in the infraorbital nerve of rat in vivo. Relation to sensory block. Anesthesiology 42:731–736 (1975).
J.E. Scurlock and B.M. Curtis. Dextran-local anesthetic interactions. Anesth. Analg. 59:335–340 (1980).
L. Langerman, E. Colombo, and S. Benita. Spinal anesthesia: Signifficant prolongation of the pharmacological effect of tetracaine with lipid solution of the agent. Anesthesiology 74:105–107 (1991).
T.L. Yaksh, J. Jang, Y. Nishiuchi, K.P. Braun, S. Ro, and M. Goodman. The utility of 2-hydroxypropyl-β-cyclodextrin as a vehicle for the intracerebral and intrathecal administration of drugs. Life Sci. 48:623–633 (1991).
T. Mashimo, I. Uchida, M. Pak, A. Shibata, S. Nishimura, Y. Inagaki, and I. Yoshiya. Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine. Anesth. Analg. 74:827–834 (1992).
A.T. Florence, P.H. Elworthy, and A. Rahman. The influence of solution viscosity on the dissolution rate of soluble salts, and the measurement of an effective viscosity. J. Pharm. Pharmac. 25:779–786 (1973).
E. Touitou and M. Donbrow. Influence of additives on (hydroxyethyl) methylcellulose properties: relation between gelation temperature change, compressed matrix integrity and drug release profile. Int. J. Pharm. 11:131–148 (1982).
C.V. Walker and J.I. Wells. Rheological synergism between ionic and non-ionic cellulose gum. Int. J. Pharm. 11:309–322 (1982).
T.P. Johnston and S.C. Miller. Toxicological evaluation of poloxamer vehicles for intramuscular use. J. Parent. Sci. Technol. 39:83–88 (1985).
J.R. Schmolka. Artificial skin. I. Preparation and properties of Pluronic F-127 gels for treatment of burns. J. Biomed. Mater. Res. 6:571–582 (1972).
L.O. Randall and J.J. Selitto. A method for measurement of analgesic activity on inflamed tissue. Arch. Int. Pharmacodyn. 11:409–419 (1957).
T.L. Yaksh and T.A. Rudy. Chronic catheterization of the spinal subarachnoidal space. Physiol. Behav. 7:1031–1036 (1976).
H. Seager. The effect of methylcellulose on the absorption of nitrofurantoin from gastrointestinal tract. J. Pharm. Pharmacol. 20:968–970 (1968).
C. Jurgensen-Eide and P. Speiser. Interaction between drugs and macromolecules. Acta Pharm. Suec. 4:185–200 (1967).
J. Rassing and D. Attwood. Ultrasonic velocity and light-scattering studies on the polyoxyethylene-polyoxypropylene copolymer Pluronic F 127 in aqueous solution. Int. J. Pharm. 13:47–55 (1983).
P-C Chen-Chow and S.G. Frank. In vitro release of lidocaine from Pluronic F-127 gels. Int. J. Pharm. 10:89–99 (1981).
L.J. Leeson. In vitro-in vivo peformance of oral controlled release dosage forms. Controlled release society, Inc., Washington DC, July 1993.
A.H. Forster and B.M. Carlson. Myotoxicity of local anesthetics and regeneration of damaged muscle fibres. Anesth. Analg. 59:727–736 (1980).
J. Kyttä, E. Heinonen, P. Rosenberg, T. Wahlström, J. Gripenberg, and T. Huopaniemi. Effects of repeated bupivacaine administration on sciatic nerve and surrounding muscle tissue in rats. Acta Anaesthesiol. Scand. 30:625–629 (1986).
L.M. Lusky and A. Nelson. Fibrosarcomas induced by multiple subcutaneous injections of carboxymethylcellulose (CMC), polyvinylpyrrolidone (PVP), and polyoxyethylene sorbitane monostearate (Tween 60). Fed. Proc. 16:318–320 (1957).
Rights and permissions
About this article
Cite this article
Paavola, A., Yliruusi, J., Kajimoto, Y. et al. Controlled Release of Lidocaine from Injectable Gels and Efficacy in Rat Sciatic Nerve Block. Pharm Res 12, 1997–2002 (1995). https://doi.org/10.1023/A:1016264527738
Issue Date:
DOI: https://doi.org/10.1023/A:1016264527738
- controlled release
- gel
- lidocaine·HC1
- nerve block
- in vitro-in vivo correlation