Atul Nayak

Potential of biodegradable microneedles as a transdermal delivery vehicle for lidocaine

There has been an increasing interest in applying biotechnology in formulating and characterising new and innovative drug delivery methods, e.g., drug-loaded biodegradable microneedles within the area of transdermal delivery technology. Recently, microneedles have been proposed for use in pain management, e.g., post-operative pain management through delivery of a local anaesthetic, namely, lidocaine. Lidocaine is a fairly common, marketed prescription-based, local anaesthetic pharmaceutical, applied for relieving localised pain and lidocaine-loaded microneedles have been explored. The purpose of this review is to evaluate the properties of biodegradable polymers that may allow the preparation of microneedle systems, methods of preparing them and pharmacokinetic conditions in considering the potential use of lidocaine for delivery through the skin.

Lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel delivery by combined microneedle and ultrasound

Abstract A study that combines microneedles (MNs) and sonophoresis pre-treatment was explored to determine their combined effects on percutaneous delivery of lidocaine from a polymeric hydrogel formulation. Varying ratios of carboxymethylcellulose and gelatine (NaCMC/gel ranges 1:1.60–1:2.66) loaded with lidocaine were prepared and characterized for zeta potential and particle size. Additionally, variations in the formulation drying techniques were explored during the formulation stage. Ex vivo permeation studies using Franz diffusion cells measured lidocaine permeation through porcine skin after pre-treatment with stainless steel MNs and 20 kHz sonophoresis for 5-and 10-min durations. A stable formulation was related to a lower gelatine mass ratio because of smaller mean particle sizes and high zeta potential. Lidocaine permeability in skin revealed some increases in permeability from combined MN and ultrasound pre-treatment studies. Furthermore, up to 4.8-fold increase in the combined application was observed compared with separate pre-treatments after 30 min. Sonophoresis pre-treatment alone showed insignificant enhancement in lidocaine permeation during the initial 2 h period. MN application increased permeability at a time of 0.5 h for up to ∼17 fold with an average up to 4 fold. The time required to reach therapeutic levels of lidocaine was decreased to less than 7 min. Overall, the attempted approach promises to be a viable alternative to conventional lidocaine delivery methods involving painful injections by hypodermic needles. The mass transfer effects were fairly enhanced and the lowest amount of lidocaine in skin was 99.7% of the delivered amount at a time of 3 h for lidocaine NaCMC/GEL 1:2.66 after low-frequency sonophoresis and MN treatment.

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

Abstract 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 1.5 mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77 cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm 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 molding 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 1.5 mm 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. Conclusions: 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.

Spreading of a Lidocaine Formulation on Microneedle-Treated Skin

The spreadability of a liquid drug formulation on skin is an indication of it either remaining stationary or distributing (spreading) as a droplet. Factors determining droplet spreadability of the formulation are spreading area, diameter of the droplet base, viscosity of the liquid, contact angle, volume of droplet on skin and any others. The creation of microcavities from the application of microneedle (MN) has the potential to control droplet spreading, and hence, target specific areas of skin for drug delivery. However, there is little work that demonstrates spreading of liquid drug formulation on MN-treated skin. Below, spreading of a lidocaine hydrogel formulation and lidocaine solution (reference liquid) on porcine skin is investigated over MN-treated skin. Controlled spreadability was achieved with the lidocaine hydrogel on MN-treated skin as compared with lidocaine solution. It was observed that the droplet spreading parameters such as spreading radius, droplet height and dynamic contact angle were slightly lower for the lidocaine hydrogel than the lidocaine solution on skin. Also, the lidocaine hydrogel on MN-treated skin resulted in slower dynamic reduction of droplet height, contact angle and reduced time taken in attaining static advancing droplets because of the MN microcavities.

Pharmaceutical Applications of Natural Polymers

This chapter covers the pharmaceutical application of natural polymers derived from carbohydrate and protein sources in modified and unmodified forms for pharmaceutical applications such as production of transdermal, percutaneous, oral and topical drug delivery systems. Hydrogel-and microgel-based drug delivery systems are also included due to their increasing importance and potential in the pharmaceutical industry. A detailed overview of the distinctive properties of natural polymers suitable for pharmaceutical applications is provided from the most recent applications reported in the literature.