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Title: Microneedle assisted percutaneous delivery of lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel
Authors: Nayak, Atul
Keywords: Lidocaine
In Vitro drug release
Drug permeation
Passive diffusion
Issue Date: 2016
Publisher: © Atul Nayak
Abstract: Local anaesthetic drugs are usually administered as symptom relieving drug formulations for the treatment of pain in superficial skin extremities. The anaesthesia is delivered into skin tissues at the site of pain because of nociceptive receptors. Concerns that exist regarding local anaesthetic drug formulations are low drug encapsulation efficiency, polydispersity of colloidal formulations, chemical interactions of released local anaesthetic drug with skin proteins and bulk viscoelastic properties. Complimenting drug formulation characteristics are the desirable rates of controlled release of drug molecules from chosen formulations pertaining to favourable in vitro skin permeation kinetics are imperative pharmaceutics based research areas because skin percutaneous delivery has distinct barrier property restrictions for passive diffusion (PD) of active molecules. Lidocaine is currently the active anaesthetic molecule of choice in local anaesthesia by clinicians because of minimum toxicity and good potency. It is a low molecular weight drug comprising of electron donating and electron withdrawing functional groups with the capacity to interact by hydrogen bonding and electrostatic interactions with several drug formulation vehicles. In this work, a naturally occurring bi-polymeric formulation was achieved with lidocaine NaCMC:gelatine hydrogel. Lidocaine NaCMC:gelatine ratio of 1:2.3 was the most favourable formulation because of faster skin permeation kinetics. Lidocaine NaCMC:gelatine 1:2.7 provided the highest drug encapsulation efficiency. This resulted in high, sustained permeation rates after adaptation of the microneedle (MN) poke and patch technique, past the stratum corneum layer of skin for quick target delivery in attaining a maximum permeation flux of near 6.0 µg/cm2/h in the hypodermis layer. Mass balance of in vitro studies using an indirect approach to quantify lidocaine permeation showed significant lidocaine permeation in skin. Subsequent vertical and horizontal (depth averaged) in vitro studies using similar MN techniques resulted in crossing minimum therapeutic level across a 10 mm radius from the epicentre of the skin sample at major reduced lag times of minutes for vertical permeation and within 0.5 hours for horizontal permeation. Furthermore, the spreadability of lidocaine NaCMC:gelatine hydrogel shows favourability in the control of droplet spreading on MN treated skin.
Description: A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.
URI: https://dspace.lboro.ac.uk/2134/21705
Appears in Collections:PhD Theses (Chemical Engineering)

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