Lidocaine hydrochloride (LidH) was formulated in sodium carboxymethyl cellulose/ gelatine (NaCMC/GEL) hydrogel and a ‘poke and patch’ microneedle delivery method was used to enhance permeation flux of LidH.
The microparticles were formed by electrostatic interactions between NaCMC and GEL macromolecules within a water/oil emulsion in paraffin oil and the covalent crosslinking was by glutaraldehyde. The GEL to NaCMC mass ratio was varied between 1.6 and 2.7. The LidH encapsulation yield was 1.2 to 7% w/w. LidH NaCMC/GEL was assessed for encapsulation efficiency, zeta potential, mean particle size and morphology. Subsequent in vitro skin permeation studies were performed via passive diffusion and microneedle assisted permeation of LidH NaCMC/GEL to determine the maximum permeation rate through full thickness skin.
LidH 2.4% w/w NaCMC/GEL 1:1.6 and 1:2.3 respectively, possessed optimum zeta potential. LidH 2.4% w/w NaCMC/GEL 1:2.3 and 1:2.7 demonstrate higher pseudoplastic behaviour. Encapsulation efficiency (14.9–17.2%) was similar for LidH 2.4% w/w NaCMC/GEL 1:1.6–1:2.3. Microneedle assisted permeation flux was optimum for LidH 2.4% w/w NaCMC/GEL 1:2.3 at 6.1 μg/ml/h.
LidH 2.4% w/w LidH NaCMC/GEL 1:2.3 crossed the minimum therapeutic drug threshold with microneedle skin permeation in less than 70 min.
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Smith BC, Wilson AH. Topical versus injectable analgesics in simple laceration repair: An integrative review. JNP. 2013;9(6):374–80.
Hogan ME, VanderVaart S, Permapaladas K, Márcio M, Einarson TR, Taddio A. Systematic review and meta-analysis of the effect of warming local anesthetics on injection pain. Ann of Emerg Med. 2011;58(1):86–98. e1.
Capellan O, Hollander JE. Management of lacerations in the emergency department. Emerg Med Clin North Am. 2003;21(1):205–31.
Bekhit MH. The essence of analgesia and anagesics. Lidocaine for neural blockade. Cambridge University Press; 2011. p. 280–281.
Chale S, Singer AJ, Marchini S, McBride MJ, Kennedy D. Digital versus local anesthesia for finger lacerations: A randomized controlled trial. Acad Emerg Med. 2006;13(10):1046–50.
Pregerson DB. Suturing and wound closure: How to achieve optimal healing. Consultant. 2007;47(12):1–7.
Braga D, Chelazzi L, Greprioni F, Dichiaranta E, Chierotti MR, Gobetto R. Molecular salts of anaesthetic lidocaine with dicarboxylic acids: Solid-state properties and a combined structural and spectroscopic study. Cryst Growth Des. 2013;13:2564–72.
Conroy PH, O’Rourke J. Tumescent anaesthesia. The Surgeon. 2013;11:210–21.
Xia Y, Chen E, Tibbits DL, Reilley TE, McSweeney TD. Comparison of effect of lidocaine hydrochloride, buffered lidocaine, diphenhydramine, and normal saline after intradermal injection. J Clin Anesth. 2002;14:339–43.
Cepeda MS, Tzortzopoulou A, Thackrey M, Hudcova J, Gandhi PA, Schumann R. Adjusting the pH of lidocaine for reducing pain on injection. Cochrane Database of Systematic Reviews 12. 2010. doi:10.1002/14651858.
Columb MO, Ramsaran R. Local anaesthetic agents. Anaesthe Intensive Care Med. 2010;11(3):113–7.
Buhus G, Poap M, Desbrieres J. Hydrogels based on carboxymethylcellulose and gelatin for inclusion and release of chloramphenicol. J Bioact Compat Pol. 2009;24:525–45.
Mu C, Guo J, Li X, Lin W, Lin D. Preparation and properties of dialdehyde carboxymethyl cellulose crosslinked gelatin edible films. Food Hydrocolloid. 2012;27(1):22–9.
Becker DE, Reed KL. Local anaesthetics: Review of pharmacological consideration. Anesth Prog. 2012;59(2):90–102.
Alvarez-Lorenzo C, Blanco-Fernandez B, Puga AM, Concheiro A. Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Adv Drug Deliv Rev. 2013. Article in press - doi:10.1016/j.addr.2013.04.016
Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges (feature article). Polym. 2008;49(8):1993–2007.
Matricardi P, Meo CD, Coviello T, Hennink WE, Alhaique F. Interpenetrating polymer networks polysaccharide hydrogels for drug delivery and tissue engineering. Adv Drug Deliv Rev 2013. Article in press – doi:10.1016/j.addr.2013.04.002
Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev. 2012;64(S):49–60.
Patel SR, Lin ASP, Edelhauser HF, Prausnitz MR. Suprachoroidal drug delivery to the back of the eye using hollow microneedles. Pharm Res. 2011;28(1):166–76.
Al-Qallaf B, Das DB. Optimization of square microneedle arrays for increasing drug permeability in skin. Chem Eng Sci. 2008;63(9):2523–35.
Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: A novel approach to transdermal drug delivery. J Pharm Sci. 1998;87(8):922–5.
Donnelly RF, Singh TRR, Woolfson D. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety. Drug Deliv. 2010;17(4):187–207.
Davis SP, Prausnitz MR, Allen MG. Fabrication and characterization of laser micromachined hollow microneedles. Transducers. 2003:1435–1438.
Zhang Y, Brown K, Siebenaler K, Determan A, Dohmeier D, Hansen K. Development of lidocaine-coated microneedle product for rapid, safe, and prolonged local analgesic action. Pharm Res. 2012;29(1):170–7.
Ito Y, Ohta J, Imada K, Akamatsu S, Tsuchida N, Inoue G, Inoue N, Takada K. Dissolving microneedles to obtain rapid local anesthetic effect of lidocaine at skin tissue. J Drug Target. 2013:1–6. doi:10.3109/1061186X.2013.811510.
Nayak A, Das DB. Potential of biodegradable microneedles as a transdermal delivery vehicle for lidocaine. Biotechnol Lett. 2013. doi:10.1007/s10529-013-1217-3.
Küchler S, Strüver K, Wolfgang F. Reconstructed skin models as emerging tools for drug absorption studies. Expert Opin Drug Met. 2013. doi:10.1517/17425255.2013.816284
Karadzovska D, Brooks JD, Monteiro-Riviere NA, Riviere JE. Predicting skin permeability from complex vehicles. Adv Drug Dev Rev. 2013;65:265–77.
Van der Maaden K, Jiskoot W, Bouwstra J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J Control Release. 2012;161(2):645–55.
Heilmann S, Küchler S, Wischke C, Lendlein A, Stein C, Schäfer-Korting M. A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds. Int J Pharm. 2013;444(1–2):96–102.
Han T, Das DB. Permeability enhancement for transdermal delivery of large molecule using low-frequency sonophoresis combined with microneedles. J Pharm Sci. 2013:1–9. doi:10.1002/jps.23662.
Auner BG, Valenta C. Influence of phloretin on the skin permeation of lidocaine from semisolid preparations. Eur J Pharm Biopharm. 2004;57(2):307–12.
Zhao X, Liu JP, Zhang X, Li Y. Enhancement of transdermal delivery of theophylline using microemulsion vehicle. Int J Pharm. 2006;327(1–2):58–64.
Kang L, Jun HW, McCall JW. Physicochemical studies of lidocaine menthol binary systems for enhanced membrane transport. Int J Pharm. 2000;206(1–2):35–42.
Poet TS, McDougal JN. Skin absorption and human risk assessment. Chem-Biol Interact. 2002;140(1):19–34.
Naidu BVK, Paulson AT. A new method for the preparation of gelatin nanoparticles encapsulation and drug release characteristics. J Appl Polym Sci. 2011;121(6):3495–500.
Al-Kahtani AA, Sherigara BS. Controlled release of theophylline through semi-interpenetrating network microspheres of chitosan-(dextran-g-acrylamide). J Mater Sci: Mater Med. 2009;20(7):1437–45.
Marquez AL. Water in oil (w/o) and double (w/o/w) emulsions prepared with spans: microstructure, stability, and rheology. Colloid Polym Sci. 2007;285(10):1119–28.
El-Mahrab-Robert M, Rosilio V, Bolzinger MA, Chaminade P, Grossiord JL. Assessment of oil polarity: Comparison of evaluation methods. Int J Pharm. 2008;348(1–2):89–94.
Chikh L, Delhorbe V, Fichet O. (Semi-) Interpenetrating polymer networks as fuel cell membranes. J Membrane Sci. 2011;368(1-2):1–17.
Jenkins AD, Kratochvíl P, Stepto RFT, Suter UW. Glossary of basic terms in polymer science. Pure Appl Chem. 1996;68(12):2304–5.
Kajjari PB, Manjeshwar LS, Aminabhavi TM. Semi-interpenetrating polymer network hydrogel blend microspheres of gelatin and hydroxyethyl cellulose for controlled release of theophylline. Ind Eng Chem Res. 2011;50(13):7833–40.
Rokhade AP, Agnihotri SA, Patil SA, Mallikarjuna NN, Kulkarni PV, Aminabhavi TM. Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine. Carbohyd Polym. 2006;65(3):243–52.
Schramm LL. Emulsions, foams, and suspensions. Wiley-VCH, 2005.128–130
Riddick TM. Control of stability through zeta potential. New York: Zeta Meter Inc; 1968.
Koul V, Mohamed R, Kuckling D, Adler HJP, Choudhary V. Interpenetrating polymer network (IPN) nanogels based on gelatin and poly(acrylic acid) by inverse miniemulsion technique: Synthesis and characterization. Colloid Surface B. 2011;83(2):204–13.
Stenson RE, Constantino RT, Harrison DC. Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation. 1971;43:205–11.
Greco FA. Therapeutic drug levels. MedlinePlus. A service of the U.S. National Library of Medicine; 2011. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/003430.htm. [Website] Accessed: 22/04/13.
Todo H, Kimurae E, Yasuno H, Tokudome Y, Hashimoto F, Ikarashi Y, et al. Permeation pathway of macromolecules and nanospheres through skin. Biol Pharm Bull. 2010;33(8):1394–9.
Victoria Klang V, Schwarz JC, Haberfeld S, Xiao P, Wirth M, Valenta C. Skin integrity testing and monitoring of in vitro tape stripping by capacitance-based sensor imaging. Skin Res Technol. 2013;19:e259–72.
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Nayak, A., Das, D.B. & Vladisavljević, G.T. Microneedle-Assisted Permeation of Lidocaine Carboxymethylcellulose with Gelatine Co-polymer Hydrogel. Pharm Res 31, 1170–1184 (2014). https://doi.org/10.1007/s11095-013-1240-z