Microneedle assisted percutaneous delivery of lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel

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

Lidocaine-loaded fish scale-nanocellulose biopolymer composite microneedles

Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture

Microneedle assisted transdermal delivery of zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations

Objective: The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT). Methods: Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77cm2 skin area (PM-3) to maintain the MN density closer to 0.6mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Results: Micro-injection moulding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17 and 3.65 fold increase in ZMT flux values were observed with 1.5mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application. Discussion: Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM. Conclusion: The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement

Effect of microneedle type on transdermal permeation of rizatriptan

The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation of rizatriptan (RIZ). Studies were carried out using two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PMs) of 0.6 mm length. In the case of the PMs, arrays were applied three times at different places within a 1.77-cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Histological studies revealed that PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 4.9- and 4.2-fold increases in the RIZ steady-state flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. A good correlation between different dimensionless parameters like the amount of RIZ permeated (Ct/Cs), thickness (h/L) and surface area (Sa/L2) of the skin was observed with scaling analyses. Numerical simulations provided further information regarding the distribution of RIZ in MN-treated skin after application of different MNs. Overall, the study suggests that MN application enhances the RIZ transdermal permeation and the geometrical parameters of MNs play an important role in the degree enhancement