Permeation Of Lidocaine Research Articles

In vitro and in vivo evaluation of a novel lidocaine-loaded cubosomal gel for prolonged local anesthesia.

Marketed lidocaine dosage forms (such as ointment, gels, and injections) used to manage acute and chronic pain showed a short duration of action (<2 h). In this study, a lidocaine-loaded cubosomal gel was prepared to sustain the release of lidocaine to prolong the local anesthetic effect (high drug retention in the skin). Lidocaine-loaded cubosomal gels were prepared by melt emulsification and sonication using Pluronic F127 and DL-α-monoolein (at different levels). The cubosomal gels were characterized by morphology, size, zeta potential, entrapment efficacy, assay, viscosity, pH, and texture profiles. Ex vivo lidocaine permeation and retention studies were performed using Sprague-Dawley rat skin. Transmission electron microscopy images confirmed the bi-continuous liquid crystalline phase with a honeycomb cubosome structure. The cubosomal particle size (103-227nm), viscosity (13,524-15,627cp), and entrapment efficacy (78.4-94.7%) increase with the level of monoolein. The ex-vivo permeation study showed a biphasic release pattern, with lidocaine cleared from ointment within 4h (97.9% cumulative release), while cubosomal gels showed sustained release up to 24h (53.33-98.86% cumulative release). A skin retention study demonstrated that cubosomes can increase (up to 28-fold) the lidocaine content in the skin (4.56mg) compared to ointment (0.19mg). A rabbit skin irritation study showed no sign of irritation after the application of cubosomal gel. In the radiant heat tail-flick study, the local anesthetic effect of lidocaine from the cubosomal gel was sustained for up to 16h with 1.43-fold higher efficacy than marketed ointment. In conclusion, the study demonstrated the potential of cubosomal nanoparticle-laden gel to sustain the release of lidocaine for prolonging local anesthetic effects for pain management.

Abstract P-2: Multiscale Molecular Dynamics Simulations of the Skin Membranes as a Tool for the Interpretation of the Transmission Electron Microscopy Images

Background: Human skin can inhibit chemical penetration which limits the clinical applications of transdermal drug delivery. The stratum corneum (SC) is the primary barrier and organized in lamellar membranes containing the lipids of ceramides (CER), free fatty acids (FFA), and cholesterol (CHOL). One of the most widely used ways to overcome the SC is the addition of chemical penetration enhancers (CPEs) to active ingredients. There are various methods, which have been employed to explore the mechanisms by which CPEs with drugs can change the morphology of SC including transmission electron microscopy. Here, we propose to use multiscale coarse-grained (CG) molecular dynamics (MD) simulations for the interpretation of the images of the SC from the electron microscopy experiments. Methods: We utilized the MARTINI force field for the CG simulations. We employed the mixed-lipid bilayer model of SC consisting of CER, CHOL, and FFA in a 1:1:1 molar ratio assembled with CHARMM-GUI web-service. The systems of the SC model membrane and various enhancers were simulated in the NPT ensemble with the polarizable water model and the reaction field approach for the long-range electrostatics with the usage of Gromacs 2019.4 software. Results: The membrane model was validated with standard characteristics: thickness, diffusion of the lipids, order parameters, and density profiles. After, we have added CPEs and active ingredients to the systems: menthol and osthole as control simulations, ethanol with linoleic acid and lidocaine as test simulations. We have observed the membrane desegregation in the case of menthol and osthole formulations similar to the published results while the permeation of lidocaine with ethanol and linoleic acid did not cause the disruption of the membranes but increased its fluidity and permeability properties. Conclusion: The method of multiscale coarse-grained molecular dynamics simulations can be utilized for the prediction and interpretation of morphology change of SC in addition to various substances.

Towards the advance of a novel iontophoretic patch for needle-free buccal anesthesia

The aim of this work was to develop a mucoadhesive iontophoretic patch for anesthetic delivery in the buccal epithelium. The patch was comprised of three different layers, namely i) drug release (0.64 cm2); ii) mucoadhesive (1.13 cm2); and iii) backing (1.13 cm2). Prilocaine and lidocaine hydrochlorides were used as model drugs (1:1 ratio, 12.5 mg per unit). An anode electrode (0.5 cm2 spiral silver wire) was placed in between the drug release and mucoadhesive/backing layers to enable iontophoresis. Surface microscopy; mechanical and in vitro mucoadhesive properties; drug release kinetics and mechanism; and drug permeation through the porcine esophageal epithelium were assessed. Topographic analysis evidenced differences in the physical structures for the several layers. All layers presented suitable handling properties i.e., flexibility, elasticity and resistance. Both the release and mucoadhesive layers presented features of a soft and tough material, while the backing layer matched the characteristics of a hard and brittle material. A synergy between the drug release and mucoadhesive layers on the mucoadhesive force and work of adhesion of the tri-layered patch was observed. Passive drug release of both drugs fitted to First-order, Hixson-Crowell and Weibull kinetic models; and the release mechanism was attributed to anomalous transport. Iontophoresis remarkably enhanced the permeation of both drugs, but mainly prilocaine through the mucosa as evidenced by the permeability coefficient parameter (3.0-fold). The amount of these amino amide salts retained in the mucosa were also equally enhanced (4.7-fold), while the application of a tiny constant electric current (1 mA·cm−2·h−1) significantly decreased the lag time for lidocaine permeation by about 45%. In view of possible in vitro / in vivo correlations, the buccal iontophoretic patch displays a promising strategy for needle-free and patient-friendly local anesthesia in dentistry.

Mucoadhesive Electrospun Patch Delivery of Lidocaine to the Oral Mucosa and Investigation of Spatial Distribution in a Tissue Using MALDI-Mass Spectrometry Imaging.

Many oral mucosal conditions cause considerable and prolonged pain that to date has been difficult to alleviate via topical delivery, and the use of injection causes many patients dental anxiety and needle-prick pain. Therefore, developing a noninjectable drug delivery system as an alternative administration procedure may vastly improve the health and wellbeing of these patients. Recent advances in the development of mucoadhesive electrospun patches for the direct delivery of therapeutics to the oral mucosa offer a potential solution, but as yet, the release of local anesthetics from this system and their uptake by oral tissue have not been demonstrated. Here, we demonstrate the fabrication of lidocaine-loaded electrospun fiber patches, drug release, and subsequent uptake and permeation through the porcine buccal mucosa. Lidocaine HCl and lidocaine base were incorporated into the electrospun patches to evaluate the difference in drug permeation for the two drug compositions. Lidocaine released from the lidocaine HCl-containing electrospun patches was significantly quicker than from the lidocaine base patches, with double the amount of drug released from the lidocaine HCl patches in the first 15 min (0.16 ± 0.04 mg) compared to that from the lidocaine base patches (0.07 ± 0.01 mg). The permeation of lidocaine from the lidocaine HCl electrospun patches through ex vivo porcine buccal mucosa was also detected in 15 min, whereas permeation of lidocaine from the lidocaine base patch was not detected. Matrix-assisted laser desorption ionization-mass spectrometry imaging was used to investigate localization of lidocaine within the oral tissue. Lidocaine in the solution as well as from the mucoadhesive patch penetrated into the buccal mucosal tissue in a time-dependent manner and was detectable in the lamina propria after only 15 min. Moreover, the lidocaine released from lidocaine HCl electrospun patches retained biological activity, inhibiting veratridine-mediated opening of voltage-gated sodium channels in SH-SY5Y neuroblastoma cells. These data suggest that a mucoadhesive electrospun patch may be used as a vehicle for rapid uptake and sustained anesthetic drug delivery to treat or prevent oral pain.

Mesoporous silica nanoparticles for enhanced lidocaine skin delivery

Lidocaine’s (Lido) low water solubility and negligible tissue uptake limit its bioavailability when applied to the skin. Nanoparticulate systems would help address these issues; therefore, lidocaine inclusion complexes with mesoporous silica nanoparticles (MSNs) were prepared and the effect of MCM41 surface functionalization with positively charged amino-propyl groups on the molecule properties studied. It is expected that positively charged nanoparticles can improve lidocaine permeation into the skin. The complexes were prepared in different lidocaine/MSNs ratios (3/1, 2/1, 1/1) and characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS) and differential scanning calorimetry (DSC). Fourier transform infrared (FTIR) spectroscopy provided detailed information regarding the molecular interaction of lidocaine with the inorganic surface. The optimized lidocaine-loaded MSNs (1/1) were used for in vitro release studies using dialysis membrane and ex vivo permeation studies by Franz diffusion cell.Higher drug release and skin permeation were observed for the functionalized complex over pure lidocaine and Lido/MCM41 which can be attributed to the electrostatic interaction between positively charged lido/MCM41-NH2 and negatively charged skin membrane cells. Therefore, MCM41-NH2 exhibited superiority over MCM41 and the free drug, suggesting the significance of functionalization in lidocaine dermal delivery.

Effective permeation of 2.5 and 5% lidocaine hydrochloride in human skin using iontophoresis technique.

Lidocaine Hydrochloride (HCL) is one of the commonest topical local anesthetic drugs. The permeation of the lidocaine can be enhanced by iontophoresis (IOP). The purpose of this study was to evaluate the permeability of 2.5 and 5% lidocaine permeation in ex vivo human skin using different IOP waveform. Continuous and modulated IOP at the current density of 0.5 mA/cm2 were applied across human skin (n = 3) in donor chamber of vertical diffusion cell at 2.5 and 5% lidocaine concentration. High Performance Liquid Chromatography was used to determine lidocaine concentration. Findings revealed that lidocaine concentration increased effectively in a time-dependent manner in both modulated and continuous IOP at 2.5 and 5% lidocaine concentration. Compared to the passive group, the flux of lidocaine with modulated and continuous IOP were higher of about six and ten-fold, respectively. However, no significant difference was observed between continuous and modulated IOP groups at both lidocaine concentrations. At 2.5% lidocaine concentration, the permeation time taken by modulated and continuous IOP to attain therapeutic levels of 142 and 164 μg/cm2 , respectively, was approximately 10 minutes. At 5% lidocaine, the therapeutic permeation of 129 and 147 μg/cm2 , respectively, was achieved at approximately 5 minutes after applying iontophoresis waveform. Study shows that modulated IOP can be a promising alternative method in clinical settings aside from continuous IOP. Based on the clinical requirements, IOP can be used at 2.5 and 5% lidocaine concentration depending on need of relatively short or very short onset action.

USE OF CASHEW BARK EXUDATE GUM IN THE PREPARATION OF 4 % LIDOCAINE HCL TOPICAL GELS

Objective: The objective of the current work was to prepare and evaluate ex vivo skin permeation of cashew bark exudate gum based 4 % lidocaine HCl topical gels.Methods: In the current work, 4 % lidocaine HCl topical gels were prepared by using different concentrations of cashew bark exudate gum, HPMC K4M, lidocaine HCl, methyl paraben (as preservative) and glycerin (as plasticizer). The formulated topical gels were evaluated for pH, viscosity, and ex vivo skin permeation through excised porcine ear skin membrane.Results: The pHs of these formulated 4 % lidocaine HCl topical gels were found within the range of 6.04±0.02 to 6.52±0.04; whereas, the viscosities were measured within the range, 4.38±0.02 x 106to 4.74±0.04 x 106 cps. Sustained ex vivo permeation of lidocaine was measured over 7 h. Highest ex vivo permeation flux was measured when 0.1 % menthol was incorporated as a permeation enhancer. It was also higher than that of the marketed 4 % lidocaine HCl topical gel. The stability study by freeze thaw cycle method revealed physically stable gels without the occurrence of syneresis.Conclusion: The results clearly indicate a promising potential of the use of cashew bark exudate gum as a gelling material with HPMC K4M to prepare 4 % lidocaine HCl topical gels of good skin permeation capability

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 36h 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.

Drug-coated microneedles for rapid and painless local anesthesia.

This study showed that drug-coated PLLA (Poly (L-lactide)) microneedle arrays can induce rapid and painless local anesthesia. Microneedle arrays were fabricated using a micro-molding technique, and the needle tips were coated with 290.6±45.9μg of lidocaine, the most widely used local anesthetic worldwide. A dip-coating device was newly designed for the coating step using an optimized coating formulation. Lidocaine coated on the arrays was released rapidly into PBS within 2min, and its stability in storage lasted 3weeks at 4, 25, and 37°C. Furthermore, the microneedle arrays showed consistent in vitro skin penetration and delivered 200.8±43.9, 224.2±39.3, and 244.1±19.6μg of lidocaine into the skin 1, 2, and 5min after application with a high delivery efficiency of 69, 77, and 84%. Compared to a commercially available topical anesthetic EMLA® cream, a 22.0, 13.6, and 14.0-fold higher amount of lidocaine was delivered into the skin. Note, in vitro skin permeation of Lidocaine was also notably enhanced by a 2-min-application of the lidocaine-coated microneedle arrays. Altogether, these results suggest that the biocompatible lidocaine-coated PLLA microneedle arrays could provide significantly rapid local anesthesia in a painless manner without any of the issues from topical applications or hypodermic injections of local anesthetics.

Lidocaine self-sacrificially improves the skin permeation of the acidic and poorly water-soluble drug etodolac via its transformation into an ionic liquid

Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements. In addition, in vitro skin-permeation testing was carried out via an ionic liquid-containing patch (Etoreat patch). The lidocaine and etodolac in ionic liquid form led to a relatively lower melting point than either lidocaine or etodolac alone, and this improved the lipophilicity/hydrophilicity of etodolac. In vitro skin-permeation testing demonstrated that the Etoreat patch significantly increased the skin permeation of etodolac (9.3-fold) compared with an etodolac alone patch, although an Etoreat patch did not increase the skin permeation of lidocaine, which was consistent with the results when using a lidocaine alone patch. Lidocaine appeared to self-sacrificially improve the skin permeation of etodolac via its transformation into an ionic liquid. The data suggest that ionic liquids composed of approved drugs may substantially expand the formulation preparation method to meet the challenges of drugs which are characterized by poor rates of transdermal absorption.

Feasibility of transdermal delivery of lidocaine-loaded nanocarriers through artificial and human skin: a pilot study

BackgroundThere is a growing demand for painless, rapid onset, long duration anaesthesia in many aspects of medicine. Nanomedicines (particles 50–500 nm) have shown promise in topical delivery of certain drugs. In this study we explored the feasibility of transdermal delivery of lidocaine across artificial membranes and human skin. MethodsThree different nanocarriers were optimised and characterised for lidocaine loading. Permeation of lidocaine was performed with modified, individually calibrated Franz cells across cellulose membrane and eyelid skin. The nanocarriers were polymeric micelles, solid lipid nanoparticles, and self-nanoemulsifying drug delivery systems (SNEDDs) or nanoemulsion. One-way ANOVA with post-hoc Tukey test was used to assess differences in permeation. FindingsSNEDD showed the highest lidocaine loading and was the most stable of all nanomedicines. Transmission electron microscope images demonstrated translucency of all suspensions with spherical morphology, which coincided with the measured particle sizes (all <200 nm). The cumulative release of lidocaine-loaded SNEDDs (277 μg/cm2 per h) and polymeric micelles (193 μg/cm2 per h) were highest across cellulose membrane, and the flux through eyelid skin was the highest with lidocaine-loaded SNEDDs (143 μg/cm2 per h) and solid lipid nanoparticles (314 μg/cm2 per h). InterpretationBecause of the lipid perturbation effects of human skin, the performance of the nanocarriers was altered compared with the artificial membrane, but overall the achieved flux for all nanomedicines was higher than that previously reported for topical anaesthetic cream tested in skin (73·81 μg/cm2 per h for lidocaine hydrochloride and 53·93 μg/cm2 per h for prilocaine hydrochloride). We have highlighted the potential capability and use of this mode of drug delivery in eyelid surgery. FundingRoyal Society.

Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro-In Vivo Correlation (IVIVC).

The present study aims to develop the correlation between in vitro and in vivo skin permeation of lidocaine in its transdermal patch. In order to minimize the run-to-run variability during in vitro skin permeation studies, release normalized cumulative percent (%Ct n) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ct n. Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUC last and C max were predicted with the established in vitro-in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for C max were found to be -30.9 and -25.4% for studies I (in vivo study in human volunteers with one batch of Lidoderm patch; internal validation) and II (in vivo study in human volunteers with another batch of Lidoderm patch; external validation), respectively, whereas minimum prediction errors in NCA method were relatively low (3.9 and 0.03% for studies I and II, respectively) compared to those in NDC method. The prediction errors for AUC last were found to be less than 2% for both methods and studies. The established method in this study could be a potential approach for predicting the bioavailability and/or bioequivalence for transdermal drug delivery systems.

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 15.7N were applied on the MN to pierce the skin. For the smaller force (3.9N), 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 3.9N at 0.25h and similarly, a 5.4-fold increase in permeation occurred at 0.5h 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 7.9N from 0.25 to 0.75h, respectively. The lateral diffusion/permeation of lidocaine for larger MN-treated force (namely, 15.7N in this work) seems to be insignificant at all recorded timings. The MN insertion force of 15.7N resulted in lidocaine concentrations slightly greater than control (passive diffusion) but significantly less than 3.9 and 7.9N 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 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.

Solvent selection effects on the transport of compounds through silicone membrane

This study evaluates the effects of donor and receptor solution composition on the transport of two model drugs, namely lidocaine and salicylic acid, across silicone membrane. Binary mixtures of buffer and propylene glycol (PG) were used as the donor vehicle and the movement of the two drugs was evaluated. The rate and extent of drug permeation was substantially influenced by the PG content in the binary mixtures with 40% PG exhibiting maximum impact. Modification of the receptor solution was also investigated whereby lidocaine permeation was reduced in a PG-based receptor phase, compared with ethanol, sub-micellar and micellar based receptor solutions. This difference was more pronounced for salicylic acid where alcohol-based receptor solutions prevented permeation whilst surfactant based (sub-micellar and micellar) receptor phases appeared to promote permeation. This enhancement is proposed to be a consequence of the drag, or pull, effect of the surfactant adsorbed on the silicone membrane in the receptor phase.

The effects of chemical and physical penetration enhancers on the percutaneous permeation of lidocaine through equine skin.

BackgroundThe effect of physical and chemical permeation enhancers on in vitro transdermal permeation of lidocaine was investigated in the horse.Therefore, the effect of six vehicles (phosphate-buffered saline (PBS), 50% ethanol, 50% propylene glycol, 50% isopropylalcohol, 50% isopropylalcohol/isopropylmyristate and 50% dimethylsulfoxide) was examined as well as the effect of microneedle pretreatment with different needle lengths on transdermal drug delivery of lidocaine.The skin was obtained from the thorax of six Warmblood horses and was stored up to two weeks at - 20°C. Franz-type diffusion cells were used to study the transdermal permeation through split skin (600 μm thickness). The amount of lidocaine in the receptor fluid was determined by UV–VIS high-performance liquid chromatography.ResultsAll investigated vehicle supplementations diminished the transdermal flux of lidocaine through equine skin in comparison to pure PBS except dimethylsulfoxide, which resulted in comparable permeation rates to PBS. The maximum flux (Jmax) was 1.6-1.8 fold lower for lidocaine applied in 50% ethanol, propylene glycol, isopropylalcohol and isopropylalcohol/isopropylmyristate. A significant higher Jmax of lidocaine was observed when lidocaine was applied in PBS onto microneedle pretreated skin with similar permeation rates in both needle lengths. After 6 hours, 1.7 fold higher recovery rates were observed in the microneedle pretreated skin samples than in the untreated control samples. The lagtimes were reduced to 20–50% in the microneedle pretreated skin samples.ConclusionMicroneedles represent a promising tool for transdermal lidocaine application in the horse with a rapid systemic bioavailability.

In Vitro Evaluation of Mucoadhesive Films for Gingival Administration of Lidocaine

The aim of this study was the optimization of a lidocaine-based film formulation for the prevention of pain from needle prick during the injection of local anesthetic in dentistry. Film performances were evaluated in vitro by studying lidocaine permeation across pig esophageal epithelium as model for nonkeratinized buccal mucosa. The results obtained showed that the molecular weight of the film-forming polymer had no effect on lidocaine transport. The introduction of the adhesive Plastoid® into the film determined a significant increase of drug permeation rate, which was further improved by the addition of Azone®. On the contrary, the effect of sodium taurocholate was negligible.

Development of cataplasmic transdermal drug delivery system containing eutectic mixture of lidocaine and prilocaine

A novel transdermal drug delivery system with the eutectic mixture of lidocaine and prilocaine was developed. The permeation of lidocaine and prilocaine proportionally increased as the weight ratio of poly(vinyl alcohol) to poly(acrylic acid) changed from 1:1 to 7:1. However, the adhesive property of the matrix significantly degraded over the ratio of 5:1. The incorporation of humectants in the matrix had a noticeable effect on the permeation of lidocaine and prilocaine. The flux of lidocaine increased as the ratio of lidocaine in the eutectic mixture increased. The permeation rate decreased significantly from the cataplasm containing 3.5:1 and 4:1 ratio of lidocaine to prilocaine due to recrystallization. When total drug concentration of the cataplasm with the ratio of 3:1 increased from 1.33 to 4 % against adhesive gel weight, the permeation of both lidocaine and prilocaine increased. However, crystallization was observed beyond 2.66 % w/w of combined drug load. Enhancers were not effective in the present study as most of the enhancer showed very low or no enhancement effect. No significant changes in the appearance and the drug content in the cataplasm were observed for 3 months.

The Effect of Alternating Current Iontophoresis on Rats with the Chronic Constriction Injury to the Infraorbital Nerve

This study aimed to examine the effect of AC iontophoresis on rats with the chronic constriction injury (CCI) to the infraorbital nerve by animal experiments. CCI model rats were divided into four groups, namely, rats that received general anesthesia for 60 min except AC IOP (CCI: n = 5), AC IOP with 0.9% physiological saline for 60 min (CCI + saline AC IOP: n = 5), AC IOP with 4% lidocaine hydrochloride for 60 min (CCI + lidocaine AC IOP: n = 5), and attachment of two electrodes soaked with 4% lidocaine hydrochloride to the facial skin for 60 min (CCI + attach lidocaine: n = 5). In the CCI + lidocaine AC IOP group, an elevated withdrawal threshold was observed after AC IOP, and the duration of efficacy was longer compared with that in the CCI + saline AC IOP and CCI + attached lidocaine groups. A significant decrease in the number of Fos-like immunoreactive (LI) cells was observed in the CCI + lidocaine AC IOP group compared with that in the CCI group. These findings suggest that the effect of CCI + lidocaine AC IOP group may be caused by active permeation of lidocaine into the facial skin and electrical stimulation of the trigeminal nucleus.

Sugar Ester J-1216 Enhances Percutaneous Permeation of Ionized Lidocaine

Percutaneous absorption enhancers affect not only the permeability of skin but also the thermodynamic properties of active ingredients in the vehicle. The present study examined the effect of J-1216, a sucrose laurate with hydrophilic–lipophilic balance = 16, on the percutaneous permeation of lidocaine (LC) from this point of view. The percutaneous permeation of LC from aqueous vehicles (pH 6.0, 7.0, 8.0, and 10.0) with or without 1.5% J-1216 was examined with excised hairless mouse skin mounted on flow-through-type diffusion cell. The permeation of LC without J-1216 increased with an increase in the vehicle pH and could be basically explained by pH-partition theory. J-1216 increased the LC permeation at pH 6.0 and 7.0 but decreased it at pH 8.0 and 10.0. The interaction between LC and J-1216 was examined using an ultrafiltration technique. J-1216 micelles interacted predominantly with unionized LC. A theoretical calculation suggested that J-1216 enhances the permeability coefficient of ionized LC, whereas it has almost no effect on that of unionized free LC. J-1216 directly affects the skin to increase the permeation of ionized LC, whereas J-1216 micelles interact with unionized LC to decrease the permeation. The effect of J-1216 is therefore a function of vehicle pH and LC concentration. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4482–4490, 2011