Development of prilocaine gels for enhanced local anesthetic action

Abstract

Prilocaine, one of local anesthetics, has been used for regional pain relief. When applied as an ointments or creams, it is hard to expect their effects to last for long time, because they are easily removed by wetting, movement and contacting. For more comfortable and better application, we developed a prilocaine gel system using a bioadhesive polymer, carboxymethyl cellulose (CMC). For suitable bioadhesion, the bioadhesive force of various polymers was tested using an auto-peeling tester. The bioadhesive force of various types of CMC such as 100MC, 150MC and 300MC, was 0.0264, 0.0461 and 0.0824 N, at 1.5% concentration, respectively. The CMC-300MC gels showed the most suitable bioadhesive forces. The effect of drug concentration on drug release was studied from the prepared 1.5% CMC gels using a synthetic cellulose membrane at 37 ± 0.5°C. As the concentration of drug increased, the drug release increased. The effects of temperature on drug release from the 1.0% prilocaine gels were evaluated at 27, 32, 37 and 42°C. As the temperature of the drug gels increased, drug release increased. The enhancing effects of penetration enhancers such as pyrrolidones, non-ionic surfactants, fatty acids and propylene glycol derivatives were studied. Among the enhancers used, polyoxyethylene 2-oleyl ether was superior. The anesthetic effects were studied by a tail flick analgesic meter. In the rat tailflick test, 1.0% prilocaine gels containing polyoxyethylene 2-oleyl ether showed the most prolonged local analgesic effects. The results support the view that prilocaine gels with enhanced local anesthetic action could be developed using CMC bioadhesive polymer.

Review of Lidocaine/Tetracaine Cream as a Topical Anesthetic for Dermatologic Laser Procedures

“…In addition, inadequate or non-uniform placement of anesthesia over the skin area, messy application, and need for a lengthy application period are other limitations of topical anesthetics [1, 2]. Ideally, topical anesthetics must be able to penetrate the relatively impermeable barrier of the stratum corneum and have minimal systemic absorption [3, 4]. …”

Comprehensive review on additives of topical dosage forms for drug delivery

“…Showed the most prolonged local analgesic effects and enhanced local anesthetic action (Kang & Shin, 2012). Acyclovir Showed enhanced iontophoretic transdermal delivery of acyclovir (ACV), a model hydrophilic smalldrug molecule, across hairless rat skin on Franz diffusion cells (Siddoju et al, 2012).…”

A simple and high‐resolution HPLC‐PDA method for simultaneous quantification of local anesthetics in in vitro buccal permeation enhancement studies

“…In this context, pharmacists and dentists have also been working together in order to overcome one of the major challenges in the field of dentistry: needle phobia (Clark and Yagiela, 2010;Sokolowski et al, 2010;Hill et al, 2013). In pursuit of this, several local anesthetic delivery systems have been designed and evaluated that aim to reduce patient anxiety during dental procedures (Hersh et al, 1996;Carr and Horton, 2001;Bågesund and Tabrizi, 2008;Chung et al, 2011;Kang and Shin, 2012;Padula et al, 2013).…”

“…The buccal mucosa of several animal species (e.g. rabbit, hamsters, dogs and swine) has been employed as biological barrier models for mimicking the human buccal mucosa in in vitro, ex vivo and in vivo drug-permeation studies (Patel et al, 2011) . Although studies dealing with the analysis of PCL or LCL in pharmaceuticals (Cereda et al, 2004;Kang and Shin, 2012;Trovatti et al, 2012;Wei et al, 2012;Cavallari et al, 2013;Padula et al, 2013;Preis et al, 2014), in biological samples (Abu-Huwaij and Assaf, 2007;Baniceru et al, 2011), after permeation through artificial membranes (Hayashi et al, 2009;Pignatello et al, 2009), excised human skin (Trovatti et al, 2012), excised mouse skin (Shicong et al, 2001;Kinoshita et al, 2003;Kang and Shin, 2012), excised rabbit ear skin (Padula et al, 2003) and excised porcine skin (Sintov and Brandys-Sitton, 2006;Pathak and Nagarsenker, 2009;Hu et al, 2011;Zhang et al, 2012), and in buccal (Ganem-Quintanar et al, 1998;Abu-Huwaij and Assaf, 2007;Kokate et al, 2008;Hu et al, 2011;Wei et al, 2012;Cavallari et al, 2013), esophageal (Padula et al, 2013) and palatal (Ganem-Quintanar et al, 1998) mucosa, have been reported, none of these has applicability for the simultaneous quantification of these compounds retained in the epithelium or after permeation of the porcine esophageal epithelium.…”