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

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 lidocaineloaded 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

Microneedle assisted permeation of lidocaine HCL from a NaCMC:gel hydrogel

Microneedle assisted permeation of lidocaine HCL from a NaCMC:gel hydroge

Microneedle-assisted permeation of lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel

Purpose 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. Methods 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. Results 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. Conclusion 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

Lidocaine permeation from a lidocaine NaCMC:gel microgel formulation in microneedle pierced skin: vertical (depth averaged) and horizontal permeation profiles

Common local anaesthetics such as lidocaine are administered by the hypodermic parenteral route but it causes pain or anxiety to patients. Alternatively, an ointment formulation may be applied which involves a slow drug diffusion process. In addressing these two issues, this paper aims to understand the significance of the ‘poke and patch’ microneedle (MN) treatment on skin in conjunction to the lidocaine permeation, and in particular, the vertical (depth averaged) and horizontal (e.g. lateral) permeation profiles of the drug in the skin. The instantaneous pharmacokinetics of lidocaine in skin was determined by a skin denaturation technique coupled with Franz diffusion cell measurements of the drug pharmacokinetics. All pharmacokinetic profiles were performed periodically on porcine skin. Three MN insertion forces of 3.9, 7.9 and 15.7 N were applied on the MN to pierce the skin. For the smaller force (3.9 N), post MN-treated skin seems to provide an ‘optimum’ percutaneous delivery rate. A 10.2-fold increase in lidocaine permeation was observed for a MN insertion force of 3.9 N at 0.25 h and similarly, a 5.4-fold increase in permeation occurred at 0.5 h compared to passive diffusional delivery. It is shown that lidocaine permeates horizontally beyond the area of the MN-treated skin for the smaller MN insertion forces, namely, 3.9 and 7.9 N from 0.25 to 0.75 h, respectively. The lateral diffusion/permeation of lidocaine for larger MN-treated force (namely, 15.7 N in this work) seems to be insignificant at all recorded timings. The MN insertion force of 15.7 N resulted in lidocaine concentrations slightly greater than control (passive diffusion) but significantly less than 3.9 and 7.9 N impact force treatments on skin. We believe this likelihood is due to the skin compression effect that inhibits diffusion until the skin had time to relax at which point lidocaine levels increase

Lidocaine NaCMC:GEL hyrdrogel delivery using combined microneedle and sonophoresis

Lidocaine NaCMC:GEL hyrdrogel delivery using combined microneedle and sonophoresi

Few-shot learning approaches for classifying low resource domain specific software requirements

With the advent of strong pre-trained natural language processing models like BERT, DeBERTa, MiniLM, T5, the data requirement for industries to fine-tune these models to their niche use cases has drastically reduced (typically to a few hundred annotated samples for achieving a reasonable performance). However, the availability of even a few hundred annotated samples may not always be guaranteed in low resource domains like automotive, which often limits the usage of such deep learning models in an industrial setting. In this paper we aim to address the challenge of fine-tuning such pre-trained models with only a few annotated samples, also known as Few-shot learning. Our experiments focus on evaluating the performance of a diverse set of algorithms and methodologies to achieve the task of classifying BOSCH automotive domain textual software requirements into 3 categories, while utilizing only 15 annotated samples per category for fine-tuning. We find that while SciBERT and DeBERTa based models tend to be the most accurate at 15 training samples, their performance improvement scales minimally as the number of annotated samples is increased to 50 in comparison to Siamese and T5 based models.Comment: 6 pages, 1 figur

Spreading of a lidocaine formulation on microneedle treated skin

Spreading of a lidocaine formulation on microneedle treated ski

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

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

Drug Utilization Evaluation of Lorazepam in Alcohol Withdrawal Syndrome Patients: A Secondary Care Teaching Hospital Based Study

Background: Drug utilization evaluation is an important parameter for the safe, effective and rational use of medications in medical care. Alcoholism results in abundant cases of alcohol withdrawal which can prove to be life-threatening if untreated, lorazepam is a drug of choice for Alcohol Withdrawal Syndrome and requires close monitoring as its over-dosing or under-dosing is common in case of withdrawal. Objective:  ensures the safe and rational use of Lorazepam in the management of Alcohol Withdrawal Syndrome. Materials and Method: This prospective, observational study was conducted among alcoholic patients admitted in the KC General Hospital, Karnataka, India. Baseline data for Clinical Institute Withdrawal Assessment for Alcohol revised scale (CIWA-Ar) was collected on the day of admission and the response to lorazepam treatment was recorded using the same with respect to the baseline data every 12th hourly after the initial administration until withdrawn. Results: Statistical analysis for 72 patients was done using ANOVA to calculate the overall progression of the syndrome with treatment. Among 72 patients 94.44% were male and 5.55% were female. The mean age of patients reported with AWS was found to be 44.90 years. A significant CIWA-Ar score reduction was observed with a p-value of <0.0001. Conclusion: Our study revealed a strong predominance of male patients with alcohol withdrawal syndrome, where maximum patients started consuming alcohol before the age of 20 years. After the administration of lorazepam, a significant CIWA-Ar score reduction was observed. Keywords: Alcohol Withdrawal Syndrome, CIWA-Ar scale, Drug utilization evaluation, Lorazepam