Lidocaine NaCMC:GEL hyrdrogel delivery using combined microneedle and sonophoresi

Atul Nayak (1253046)

Diganta Das (1254000)

Tao Han (1255185)

English

Loughborough University Institutional Repository

    This item was submitted to Loughborough’s Institutional Repository (https://dspace.lboro.ac.uk/) by the author and is made available under the following Creative Commons Licence conditions.       For the full text of this licence, please go to: http://creativecommons.org/licenses/by-nc-nd/2.5/  99.7099.7599.8099.8599.9099.95100.000 1 2 3F4 PDF4MN 3minsF4 MN 5minF4 LFS 5min15WF4 LFS 10min18WF4 MN + LFS%remaining in skinTime (Hr) LIDOCAINE NaCMC:GEL HYDROGEL DELIVERY USING COMBINED MICRONEEDLE AND SONOPHORESIS  Atul Nayak, Tao Han, Diganta Bhusan Das   Chemical Engineering Department, Loughborough University,  Loughborough,UK. (Emails: A.Nayak@lboro.ac.uk; T.Han@lboro.ac.uk; D.B.Das@lboro.ac.uk)  Lidocaine hydrochloride (HCl) is a water soluble weak acidic, local anaesthetic, usually administered by injection into the dermis layer of skin causes pain1,2. Alternatively an eutectic mixture of local anaesthetics (EMLA) may be unsuitable in emergency situations because a 1 hour time duration of permeation is necessary3,4. Low frequency sonophoresis (LFS) within a range of 20-100 kHz allows for the mechanism of inertial cavitation as the accepted theory for enhancing skin permeability5,6. Additionally a minimally invasive mechanism of microneedle assisted delivery of topical drugs produces microconduits to bypass the stratum corneum (SC) layer of skin7. Jacketed Franz diffusion cells (FDC) were implemented for ex-vivo skin permeation studies of lidocaine NaCMC/GEL hydrogels post treatment by combined microneedle insertion followed by sonophoresis8. A lidocaine GEL to NaCMC mass ratio of 2.66 hydrogel treated with 18W LFS for a 10 minute duration combined with microneedle treatment of 5 minute duration resulted in a 4.8 fold average increase over 30 minutes when compared with LFS or passive diffusion alone. Minimum therapeutic levels of lidocaine HCl at 1.5 µg/ml were crossed after a period of 7 minutes post microneedle insertion of 5 mins and 18 W LFS for GEL to NaCMC mass ratio 2.66. A fairly significant and steady decline in the percentage of lidocaine HCl contained in skin from mass balance determination revealed lidocaine GEL to NaCMC mass ratio of 2.66 to possess 99.7% lidocaine HCl within 3 hours. This is likely caused by lidocaine HCl molecules diffusing faster through cavity formed cellular features in skin before systemic clearance in hypodermis or capillaries. The dispersion trends from zeta potential analysis favour lidocaine HCl GEL to NaCMC mass ratios from 1.6 to 2.3 compared with 2.66 of a lot more agglomeration. Increased GEL to NaCMC mass ratios resulted in fairly significant increases in mean particle size diameters despite polydispersity observed with all GEL to NaCMC mass ratios of lidocaine.                       References   1. M.L. González-Rodríguez, L.B. Barros, J. Palma, P.L. González-Rodríguez, A.M. Rabasco “Application of statistical experimental design to study the formulation variables influencing the coating process of lidocaine liposomes” Pharmaceutical Nanotechnology., 337, 336–345 (2007). 2. K.B. Colaric, D.T. Overton, K. Moore “Pain reduction in lidocaine administration through buffering and warming” American Journal of Emergency Medicine., 16, 353-356 (1998). 3. A. Nayak, D.B. Das “Potential of biodegradable microneedles as a transdermal delivery vehicle for lidocaine” Biotechnol Lett., 35, 1351-1363 (2013). 4. Y. Zhang, K. Brown, K. Siebenaler, A. Determan, D. Dohmeier, K. Hansen “Development of lidocaine coated microneedle product for rapid, safe, and prolonged local analgesic action” Pharm Res., 29, 170-177 (2012) 5. B. Polat, D. Hart, R. Langer, D. Blankschtein “Ultrasound-mediated transdermal drug delivery: mechanisms, scope, and emerging trends” J Control Release., 152, 330-348 (2011). 6. G. Merino, Y.N. Kalia, M.B. Delgado-Charro, R.O. Potts, R.H. Guy “Frequency and thermal effects on the enhancement of transdermal transport by sonophoresis” J Control Release., 88, 85-94 (2003) 7. H.S. Gill, M.R. Prausnitz “Coated microneedles for transdermal delivery” J Control Release., 117, 227-237 (2007) 8. A. Nayak, D.B. Das, G.T. Vladisavljević “Microneedle assisted permeation of lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel” Pharm. Res., 30, 1-15 (2013)  Fig. 2   Example of Particle size distribution of lidocaine NaCMC/gel hydrogels Fig. 1  Example of lidocaine HCl contained in skin from (F4) NaCMC/GEL 1:2.66 (  Passive diffusion), (  Microneedles, 3 min), (    Microneedles, 5 min), (     LFS 5 min 15 W), (   LFS 10 min 18 W), (      Microneedles + LFS)   

Lidocaine NaCMC:GEL hyrdrogel delivery using combined microneedle and sonophoresis

https://repository.lboro.ac.uk/articles/Lidocaine_NaCMC_GEL_hyrdrogel_delivery_using_combined_microneedle_and_sonophoresis/9245753/files/16829612.pdf

Lidocaine NaCMC:GEL hyrdrogel delivery using combined microneedle and sonophoresis

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