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The study drew attention to the influence mechanism of propofol and lidocaine hydrochloride nanoemulsion (NE) in the retinal ganglion cell pathology in diabetic rats. Specifically, the propofollidocaine hydrochloride NE was prepared using the emulsification method. The microscope and laser particle size analyser were used to observe the morphology and particle size of NE, respectively. Also, the viscosity of the NE and the recovery rate of the main ingredient were explored. 45 adult male Wistar rats were randomly divided into control group (PBS control), model group (diabetes model), and test group (diabetes model+propofol-lidocaine hydrochloride NE), with 15 rats in each group. The three groups were compared for the blood glucose, body weight, TNF-α and IL-1β mRNA levels in retinal tissue, and the number and apoptosis rate of ganglion cells. It was found that the average particle size of the NE was 89.76 nm, the maximum absorption wavelength was 280.0 nm, and the viscosity was 106.49 N/m/s. The average recovery rate of propofol in NE was 99.91%, and that of lidocaine hydrochloride was 99.80%. At 12th week after modeling, the blood glucose of the test group was lower versus the model group (P < 0.05); the blood glucose and body weight of rats in the control group were lower than those in the other two groups (P < 0.001). The test group exhibited lower mRNA levels of TNF-α and IL-1β and apoptosis index of retinal ganglion cells versus the model group (P < 0.05). The model group showed a lower number of retinal ganglion cells versus the other two groups (P < 0.05). It was inferred that propofol-lidocaine hydrochloride NE of a small particle size and good syringeability can notably reduce blood glucose, TNF-α and IL-1β mRNA levels, and retinal ganglion cell apoptosis index, and at the same time increase the number of retinal ganglion cells.

This present work describes the possible advantages of carboxymethylcellulose (CMC) blending with ball-milled glutinous starch (BMGS) on the modification of release and penetration of model water-soluble active ingredient, lidocaine hydrochloride, from the blended matrix. The 20–67% CMC mass containing CMC-BMGS matrices were fabricated by casting the aqueous dispersion of CMC-BMGS onto the tray and oven-dried. BMGS and CMC were compatible as revealed by SEM and ATR-FTIR. Irrespective of the CMC mass, all CMC-BMGS matrices showed comparable matrix mass, thickness, moisture content, moisture absorption as well as mechanical and mucoadhesive properties. The surface pH of CMC-BMGS tended to increase with the CMC mass. Depends on CMC mass, matrix properties, release, and penetration rates were modulated significantly. CMC had shown a substantial role in the swelling and erosion behaviors of BMGS films, and thus modulated the release and penetration significantly. The release and penetration mechanisms of active ingredient from the CMC-BMGS matrices were Fickian diffusion-controlled, with rates of release and penetration ranging from 2.05 ± 0.21 to 7.55 ± 1.08%/min½, and from 3.48 ± 0.28 to 8.04 ± 0.64 μg/cm2/min½, respectively. The capability of CMC-BMGS matrices as mucoadhesive delivery systems to provide sustained delivery of water-soluble active ingredients was disclosed.

A unique facile process has been adopted for fast assembly of a poly(N-vinyl imidazole) cross-linked β-cyclodextrin hydrogel through microwave-assisted free radical polymerization, using N,N'-methylenebis(acrylamide) cross-linker. The copolymer possesses positive surface charge, one of the characteristic properties of an ideal hemostatic hydrogel. The functionalized imidazole-based hydrogel demonstrates rapid, superior blood coagulation kinetics under in vitro and in vivo conditions. On application to a major renal arterial hemorrhagic model, this hydrogel shows better blood clotting kinetics, leading to complete hemostasis in as few as ∼144 ± 7 s. Additionally, 350 μL of whole blood was clotted instantly, in ∼35 s, and therefore, reinforcing its hemostatic potential. The hydrogel demonstrates excellent biocompatibility, when seeded with human dermal fibroblast cells, retaining the native property of its predecessor. In addition, the hydrogel presents excellent hemocompatibility when tested with whole blood with the highest hemolytic ratio of 1.07 ± 0.05%. Moreover, it also demonstrates potential as a carrier for sustained release of an anesthetic drug, lidocaine hydrochloride monohydrate (∼83% in 24 h). The rapid hemostatic behavior of the hydrogel is coupled with its cytocompatibility and hemocompatibilty properties along with controlled drug release characteristics. These behaviors evidently demonstrate it to be an excellent alternative for a superior hemostatic material for severe hemorrhagic conditions.

Multicomponent analysis using overlapped spectra presents a great challenge in pharmaceutical quality control analysis. The present study was aimed to develop a simple and accurate UV spectrophotometric method for the determination of diclofenac sodium in the presence of lidocaine hydrochloride in an injectable dosage form. The proposed method is based on the simultaneous analysis of diclofenac sodium and lidocaine hydrochloride using two wavelengths (276 nm and 235 nm). Method validation was conducted in accordance with the ICH guidelines. The Beer-Lambert law was obeyed in a concentration range of 6 – 24 and 1.6 – 6.4 μg/mL for diclofenac sodium and lidocaine hydrochloride, respectively, with correlation coefficient not less than 0.996. It proved to be a precise method (RSD% < 3%, n = 6) with good recovery results, which reflects the freedom of interference with lidocaine and other excipients. Thus, the developed method has proved to be accurate and valid for the simultaneous analysis of diclofenac sodium and lidocaine hydrochloride.

Dry socket disease, a pocket wound caused by the tooth extraction that resulted in severe acute pain which requires a topical analgesic with rapidly pain reduction and suppress the pain until the wound healed. This study aimed to investigate factors affecting gelation temperature and gelation time of lidocaine hydrochloride (LH)-loaded polyelectrolyte complex (PEC) thermosensitivity gel for treating dry socket wound. The first factor was investigated the effects of the ratio of three different types of polymers as chitosan (CS), hyaluronic acid (HA) and poloxamer407 (P407) on the phase transition caused by temperature. The second factor was examined the effects of gel preparation methods. The results showed that increasing concentration of the cationic polymer as CS induced the separation of the solution to gel (sol-to-gel) system due to the charge of CS and the charge of PEC. The ratio of HA:P407 affected the gel forming which high concentration of P407 reduced the gelation temperature while low concentration of HA disturbed the sol-to-gel state causing coagulation. The viscosity, spreadability, and swelling were significantly increased due to the concomitant increased in each polymer, HA and P407. The particle of the formulation observed under microscope was found to be less than 1 µm. Phase inversion from sol-to-gel was found after a min at 23°C. Since gelation temperature of the purposed formula is supposed to form gel below 37°C within a short period of injection. The results of the study indicate the suitable sol-to-gel forming in the appropriate temperature and time which should be used for further investigation in the efficacy and safety.

Hypothesis: Common amphiphilic drug molecules often have a more rigid nonpolar part than conventional surfactants. The rigidity is expected to influence the self-assembling properties and possibly give rise to aggregation patterns different from that of regular surfactants. Experiments: We have investigated self-assembling properties of the hydrochloride salts of adiphenine (ADP), pavatrine (PVT), and amitriptyline (AMT) at concentrations up to 50 wt% using small-angle x-ray scattering, dynamic light scattering, cryo-transmission electron microscopy, and surface tension measurements. Findings: All drugs form small micelles of oblate spheroidal shape at concentrations above the critical micelle concentrations (CMC). The micelles grow weakly in size up to about 20 wt%, where the aggregation number reaches a maximum followed by a slight decrease in size at higher drug concentrations. We observe a correlation between the decrease in micelle size at high concentrations and an increasing charge of the micelles, as the degree of ionization increases with increasing drug concentration and decreasing pH. In contrast to what has previously been reported, the aggregation behavior of all studied drugs resembles the closed association behavior of conventional surfactants with a short aliphatic chain as hydrophobic tail group i.e. the micelles are always small in size and lack a second CMC. CMC values were determined with surface tension measurements, including also lidocaine hydrochloride (LDC) and chlorpromazine hydrochloride (CHL).

Medicinal aerosols for external use are a less popular form of the drug than aerosols for internal use, i.e., inhalation aerosols. Most common are dermal and nasal aerosols. If the aerosol is used on damaged skin, it must be sterile. Aerosols intended for use on damaged epidermis form a bandage after spraying, protecting the wound from external contamination. The use of natural polymers such as alginates is also widespread in the treatment of wounds and burns. Alginates gel creates hydrogels with a high degree of hydration. This process happens by adding electrolytes. A moist environment promotes proper wound healing processes. What is more, bandages reduce the risk of wound infection. The aim of this work was to develop the composition and technology of manufacture for an aerosol gel based on the natural polymer such as sodium alginate. The active ingredient used as a topical anesthetic in the formulations was lidocaine hydrochloride in 1% concentration. It is characterized by a local anesthetic effect and is used in creams, ointments, and gels commercially available in pharmacies. After the aerosol is sprayed on the surface, the gel covers it evenly and does not need to be spread. The form of a gel gives a feeling of cooling to the burned area, and lidocaine hydrochloride is designed to anesthetize it additionally. Rheological evaluation of the obtained gels was a performer. Effects of the addition of the active substance and excipients on the viscosity of the formulations were investigated. The efficacy of antimicrobial preservation was assessed to select the preservative. In addition, the amount of propellant and a suitable valve and spray atomizer were also chosen for each aerosol to reduce the foaming effect. Quantitative determination of the active substance present in the aerosol composition was performed using high-performance liquid chromatography (HPLC) with isocratic elution. The method used was validated for specificity, accuracy, precision, and linearity. Based on the calibration curve, limits of detection and quantification (LOD and LOQ) for lidocaine hydrochloride were also calculated. The optimal concentration of sodium alginate in the developed gel is 0.6%, which was confirmed by the viscosity test results. The preservative was bronopol in concentration 0,01%. Isopropanol and colloidal silica were included in the formulation to reduce the foam created after the aerosol was sprayed on the substrate. The amount of propellant in relation to the amount of the gel was around 10:90 (m/m).

Objective: To investigate and analyze the anesthetic effect of compound artevacaine hydrochloride in patients undergoing oral implantation. Methods: In this study, 60 patients receiving oral implant surgery in our hospital were selected as the research subjects, and the operation time was from July 2019 to March 2021. Patients were randomly selected and divided into groups for the study. 30 patients receiving lidocaine hydrochloride anesthesia were used as the control group, and 30 patients receiving compound artevacaine hydrochloride anesthesia were used as the research group. The anesthetic effect and safety of the two groups were compared and analyzed. Results: The anesthetic effect of the study group was significantly better than that of the control group (P < 0.05). The blood pressure and heart rate in the study group were significantly lower than those in the control group (P < 0.05). There was no significant difference in blood pressure and heart rate between the two groups before anesthesia (P > 0.05). There was no significant difference in the incidence of ADR between the two groups (P > 0.05). Conclusions: For patients undergoing oral implant surgery, choosing compound artevacaine hydrochloride as anesthetic drug has obvious anesthetic effect and can stabilize patients' life indexes. The anesthetic effect is obvious, and there is no obvious adverse reaction, and the clinical value is obvious.

In the present day circumstances, it has been reported that the Dental diseases are a most important physical condition problem in all parts of the globe, general in all age groups, races and genders. The proportion of dental diseases has developed to a great extent in current years. Around 70% of inhabitants suffer from dental problems. The human population is exaggerated by foremost of oral diseases. To treat dental problems such as pain due to dental caries, periodonitis, gingivitis, and other gum infections, painkillers alongside with antibiotics and various dental paints are the generally prescribed drugs by dentists as primary mode of treatment. However the general side effects of most of the painkillers are hyperacidity and gastric annoyance upon oral administration. On the other hand, nearly all antibiotics due to measured onset of action and hepatic “first-pass” consequence fail to construct prompt and extend actions. Furthermore, most of the dental formulations are washed out by saliva inside a few hours of application. To conquer the above-mentioned problems, a soft polymeric mold containing antibiotic and anasthetics drugs and having a suitable constancy to stick to the tooth, was developed for continued drug release to endow with improved relief in dental patients. Carbopol 934, Ethyl cellulose, Gum tragacanth, Hydroxy propyl cellulose, and PEG 400 were used to organize the formulation containing Lidocaine hydrochloride and doxycycline hyclate individually and in combination, by addition and solvent evaporation technique. Dissimilar physicochemical characterization studies such as mucoadhesion test and swelling index were conceded out. In vitro drug release studies showed sustained release of Lidocaine hydrochloride and doxycycline hyclate in simulated saliva for 24 h. Additional studies are necessary to succeed with these formulations in humans. Upon accomplishment, this type of dosage form may open up new avenues towards dentistry.

The objective of the present work is to develop a simple, precise, accurate, validated stability indicating RPHPLC method for the determination of Phenazone and Lidocaine hydrochloride in bulk and tablet dosage form. The HPLC separation was achieved on Agilent TC C18 (2) 250 x 4.6 mm, 5 m column using mobile phase composition of phosphate buffer pH 2.5, acetonitrile, Methanol 70:20:10 (V/V/V). Flow rate was maintained at 1.5 ml/min at an ambient temperature. Quantification was achieved with ultraviolet detection at 230 nm. The retention time obtained for Lidocaine hydrochloride was at 7.2 min of and Phenazone was at 10.1 min. The result obtained with the detector response was found to be linear in the concentration range of 50-150 mg/ml for Phenazone and 10-70 mg/ml for Lidocaine Hydrochloride. The reliability and analytical performance of the proposed methods, including linearity, range, precision, accuracy, detection and quantitation limits, were statistically validated. When of Phenazone and Lidocaine hydrochloride was subjected to different stress conditions; the proposed methods could effectively separate the drug from its degradation products, and were thus considered as good stability-indicating procedures. It is concluded that this method can be applied for routine quality control of Phenazone and Lidocaine Hydrochloride in dosage forms as well as in bulk drug. Keywords: Phenazone, Lidocaine hydrochloride, Lidophen ear drop, Method development and validation, Stability indicating.

Developments aimed at expanding knowledge in the health area make it possible to increase human life expectancy. Calcium phosphate cement is a good option as a carrier for drug delivery systems because it is possible to achieve biocompatibility and adequate porosity in the same material. Utilization of this ceramic matrix is necessary to control the drug dosage released during contact between the bioceramic and host organism, and to promote bone regeneration. The techniques currently used to calculate the amount of drug released from the calcium phosphate cement in a drug delivery test have some drawbacks, such as limited sensitivity and loss of sample during measurements. Considering the reduction of the amount of sample used to determine the percentage of drug released and the use of a non-destructive technique with high sensitivity, the proposed work uses electrochemical impedance spectroscopy as a method to determine the phenomenon of interaction between the drug and the matrix. The matrix immersed on the phosphate buffer solution (PBS) is calcium phosphate cement with 1% of lidocaine hydrochloride. The results show changes in the R(RQ)(RQ)(RQ) equivalent circuit values obtained by the Nyquist diagrams of the samples that had their resistance values elevated due to the interaction between the drug and PBS/calcium phosphate cement, which causes correlation between the drug released presented on the PBS and variation in the electrical properties of the system.

Background Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the “Danish quality scheme”; a voluntary initiative taken by the Danish pig industry. The approved procedure for local anaesthesia in Denmark is a three-step injection method with procaine. A comparison of lidocaine and procaine with the same concentration and injection methods of local anaesthetics has not previously been studied. The purpose of this study was to investigate the effect of two injection methods and two local anaesthetics on piglets’ avoidance behaviour (vocalisation and resistance movements) as well as the time spent on the procedures. The study included 203 male piglets that were randomly assigned to one of five treatments: 1. Control: Sham-handling without injection of local anaesthesia, 2. Pro3: Procaine injection using a three-step method, 3. Pro2: Procaine injection using a two-step method, 4. Lid3: Lidocaine injection using a three-step method, 5. Lid2: Lidocaine injection using a two-step method. During injection of local anaesthesia and castration, vocalisation was measured using a decibel meter and resistance movements were registrated by video recordings. Results During castration, piglets treated with local anaesthesia showed significantly reduced vocalisation and resistance movements and time spent on castration was also significantly reduced compared to the control group. During injection of the local anaesthesia, the piglets had significantly increased vocalisation and resistance movements compared to the control group. Piglets injected with lidocaine had a significantly reduced resistance movement score and a tendency to reduced vocalisation compared to piglets injected with procaine. No differences in avoidance behaviour were found between the injection methods. Conclusions The use of local anaesthesia, irrespective of the method and local anaesthetic, was effective in reducing vocalisation and resistance movements during surgery as well as the time spent on castration.

The present study deals with the formulation of mucoadhesive bilayered buccal film of lidocaine hydrochloride and benzydamine hydrochloride for treatment of oral ulcers (aphthous stomatitis). Eudragit-RLPO and Ethyl cellulose were used as film forming polymers and low viscosity grade hydroxyl propyl cellulose as a mucoadhesive agent. Solvent casting method was adopted for film formation. The film was evaluated for content uniformity, tensile strength, folding endurance, swelling, mucoadhesive strength, ex vivo mucoadhesive time and in vitro drug release. The films were characterized for DSC and FTIR. The film showed acceptable film properties and muco-adhesion. The formulation showed predictive drug release, i.e. 80 in 2, 4 and 6 h respectively. In-vitro drug release study revealed that a combination of Eudragit and Ethyl cellulose was required for better control of the drug release. The DSC and FTIR study confirmed drug-drug and drug–excipient compatibility. Keywords: Bilayer film, Eudragit-RLPO, Ethyl cellulose, Muco-adhesion, Extended drug release.

BACKGROUND AND OBJECTIVES Vasospasm is a thorny problem often encountered in microvascular surgery that seriously threatens the survival of vascularized tissue transfers. This investigation is dedicated to establishing a model of vasospasm and to evaluating the antispasmodic efficacy of 10 pharmacologic agents. STUDY DESIGN/MATERIALS AND METHODS Eighty Sprague-Dawley rats were used. After anesthesia and depilation, the femoral neurovascular bundle was exposed, and a pair of microsurgical forceps were used to trigger vasospasm of the femoral vessels by blunt dissection. Then, 10 pharmacological agents, namely, prostaglandin E1, sodium nitroprusside, magnesium sulfate, papaverine, normal saline, phentolamine, verapamil, 2% lidocaine hydrochloride, amrinone, and 12% lidocaine hydrochloride, were dripped to the femoral vessels, after which laser speckle contrast imaging was used to collect perfusion images, acquiring the perfusion and the inner caliber of the femoral vessels at multiple timepoints. Furthermore, blood perfusion and the time consumed to escape vasospasm and reach hyperperfusion in each group were calculated. The difference of spasmolytic efficacy among the agents was statistically analyzed by one-way analysis of variance. RESULTS There was a significant difference in antispasmodic ability among the 10 agents (P

Introduction: To investigate the effect of resultant precipitate formed on interaction between 2% lidocaine hydrochloride (with adrenaline) (LA) with 3% sodium hypochlorite (NaOCL) and 2% chlorhexidine (CHX) on root canal dentin after chemomechanical preparation using scanning electron microscopy (SEM). Methods: Thirty six mandibular premolars were decoronated, and the root length was standardized. All specimens were randomly distributed into the following three groups: Group I (control): 2% LA mixed with sterile water. Group II: 2% LA with 3% NaOCL, Group III: 2% LA with 3% CHX. In all groups mechanical instrumentation with rotary files was done. Teeth samples were sectioned into three parts, split and SEM analysis of root canal wall was done at cervical. Middle, and apical root thirds. Results: SEM images revealed patent dentinal tubules with no precipitate occlusion in group I and group III, whereas there was occlusion of dentinal tubules with a precipitate in group II at all the three root levels studied. Conclusions: The precipitate formed on the interaction between 2% LA solution with 3% NaOCL tends to occlude the dentinal tubules at the coronal, middle, and apical root thirds. The chemomechanical rotary instrumentation procedure did not effectively remove the precipitate from all the three root levels of the specimens studied. LA/sterile water group and LA/CHX group did not result in any precipitate formation on root canal dentin.

Traditional pharmaceutical manufacturing is based on a complex supply chain that is vulnerable to spikes in demand and interruptions. Continuous pharmaceutical production in compact modules is a po...

Antihemoroid® suppository has been produced commercially by PT. Kimia Farma, Indonesia. For QC purposes, a separated densitometric method for analysis of its active ingredients, lidocaine hydrochloride and hexachlorophene, was applied. The objective of this study was obtaining more efficient analysis method of LH and HC, therefore an HPLC procedure has been developed for the determination of both compounds simultaneously. AYMC-Triart C18 column was used with a gradient mobile phase consisting of acetonitrile and phosphate buffer 0.05 M (pH 6.0). Quantitative evaluation was performed at 220 nm. Method validation was performed according to the new methods of USP 41. Result showed that the HPLC method was simple, accurate, precise, and robust. The HPLC method can be applied in simultaneous determination of LH and HC in suppositories as a QC tool in the pharmaceutical industries.

In the current investigation, a number of chromatographic methods with the accurate, precise and specific criteria have been developed and validated for diclofenac sodium and lidocaine hydrochloride Commitment of their large quantities ampule of pharmaceutical dosage form. The High-Performance Liquid Chromatography (HPLC) system was performed at 25 ° C; with appropriate chromatographic isolation accomplished through the use of Waters Symmetry SB-C7 column with a mobile phase containing 0.1 M sodium acetate and methanol (40:60) (v/v). During development the portable stage was delivered at a stream rate of 1 mL/min, the wavelength was adjusted at 254 nm. First of all, the retention times for diclofenac sodium and lidocaine HCl were about 4.1 and 10.8 min accordingly. A performance and technical demonstration of the suggested Revers phase-HPLC method has been numerically challenged with support to process appropriateness, verticality, scales, simplicity, repeatability, sensitivity, stability, discovery and limits of quantification. In addition, the calibration curves for diclofenac sodium active pharmaceutical ingredient (API) with linear regressions > 0,999895 obtained linear in the distances 1870-5600 ?g / mL. Moreover, for determining of lidocaine HCl drug, a range of 500 - 1500 ?g/mL of working standard was used, the result showed for lidocain HCl that a linear curve with correlation coefficients of > 0.99980. Finally, the both drugs were isolated and resolute with selective and stable characteristics by the proposed technique. In the conclusion, successful validation of the HPLC approach has been demonstrated with high precision and accuracy for the assessment of both the mixed dosage form type of both diclofenac sodium and lidocaine HCl.

To investigate the effect of calcium hydroxide mixed with lidocaine HCl on postoperative spontaneous pain.Sixty patients having irreversible pulpitis and symptomatic apical periodontitis with a preoperative spontaneous pain and percussion pain which was more than 50 on a visual analogue scale (100 mm VAS) were included in this study. After the preparation of the root canals, the patients were randomly distributed into two groups according to the calcium hydroxide vehicle, control group (mixed with saline) and calcium hydroxide mixed with lidocaine HCl (n = 30). Postoperative spontaneous pain scores were recorded by a VAS every day for a week. Data were analysed using one-way analysis of variance, chi-squared test and Mann-Whitney U tests (p = 0.05).The calcium hydroxide mixed with lidocaine HCl group resulted in significantly less pain compared with the calcium hydroxide mixed with saline group during days 1 to 4 (p 0.05). There were no significant differences between the groups in terms of postoperative percussion pain levels (p 0.05).Within the limitations of this study, it can be concluded that the calcium hydroxide mixed with lidocaine HCl can be beneficial in reducing postoperative pain in teeth with irreversible pulpitis and symptomatic apical periodontitis.The calcium hydroxide mixed with lidocaine HCl can be beneficial in reducing postoperative pain in teeth with irreversible pulpitis and symptomatic apical periodontitis.TCTR20181121003.

Alveolar osteitis is a complication that can occur after tooth extraction, whereby exposed bone results in severe throbbing pain for the patient and can be prone to infection. The current treatment options are widely regarded as sub-optimal. The aim of this project was to investigate in vitro the plausibility of a dual-action monolithic drug-loaded thermosensitive hydrogel that undergoes thermal gelation within the tooth socket and releases both anaesthetic and antimicrobial agents. Hydrogels containing different levels of lidocaine HCl and metronidazole were prepared based upon Carbopol 934P NF and Pluronic F-127 blends. Membrane-less drug release was determined from the set hydrogels into phosphate buffered saline (PBS) at 37 °C as a function of time, following analysis by HPLC. Gelation characteristics and hydrogel dissolution characteristics were also determined. At 23.38% Pluronic F-127, sol-gel transition commenced at 23 °C and gelation was completely at 37 °C (physiological temperature). Setting times varied with Pluronic content and there was an inverse relationship between drug release and Pluronic content. Sustained and dose dependent release of both drugs was observed at therapeutically relevant levels over 24 h, via a combination of diffusion, dissolution and surface erosion processes. Based on the amounts of drugs released, it was determined that hydrogels containing up to 0.5% lidocaine and 0.1% metronidazole exhibited low risk of cytotoxicity to primary human gingival fibroblasts. In an in vivo scenario, the sol-phase formulation would make contact with all inner surfaces of a tooth socket prior to transitioning to monolithic gel-phase and provide sustained release of lidocaine and metronidazole at sub-toxic levels, thereby providing simultaneous pain relief, protection from ingress of debris and potentially pathological bacteria.

An HPLC-UV method for quantitative determination of lidocaine and miramistin in a combination wound-healing gel is reported. The method was validated for specificity, linearity, accuracy, and precision. The linear range for lidocaine hydrochloride was 0.08 – 0.12 mg/mL; for miramistin, 0.04 – 0.06 mg/mL. The linear correlation coefficients were 0.9992 and 0.9996 for lidocaine hydrochloride and miramistin, respectively. The method could be used for quantitative evaluation of lidocaine and miramistin in combination medicines.

Using Chitosan/PEO as the shell and PCL as the core, chitosan-polyethylene oxide/polycaprolactone nanofibrous mats were prepared successfully by coaxial electrospinning for co-load and sequential co-delivery of two drugs. Herein, lidocaine hydrochloride (Lid), used for pain relief, was added to the shell, and curcumin (Cur), an anti-inflammatory agent, was introduced into the core. Sodium bicarbonate (SB) was also added to the core layer to provide wound microenvironment sensitivity. Under acidic conditions, Lid was released due to the formation of -NH3+ by protonation of -NH2 on the chitosan molecular chains. At the same time, SB reacted with hydrogen ions to generate CO2, and many holes were generated on the surface of the fibers, providing more discharge paths for Cur release. Additionally, both Lid in the shell layer and Cur in the core layer exhibited acidic pH (∼5.4)-responsive release profiles. Moreover, a rapid release of Lid and a sustained release of Cur were observed to provide the immediate effects of analgesia and long-term antibacterial activity in the process of wound healing. Furthermore, after 48 h incubation, the mats showed continuous and excellent antibacterial performance against E. coli and S. aureus. The results of blood coagulation showed that the mats could achieve rapid hemostasis in the early stage of wound formation. Hemolytic and cytotoxicity evaluation also revealed that the mats had excellent hemocompatibility and cytocompatibility. Therefore, this study has made invaluable contributions to the design of a dual-drug-loaded dressing with microenvironment-responsive and sequential release properties towards wound care.

The aim of this study was to confirm the feasibility of gelatin/gelatinized tapioca starch (α st) films for buccal delivery and to evaluate their irritancy. Lidocaine (LB) and lidocaine hydrochloride (LH) were used as model drugs and glycerin was used as the plasticizer. The scanning electron microscopy, atomic force electron microscopy, X-ray diffraction and thermogravimetric analysis results confirmed the compatibility of gelatin/α st/glycerin (Gαgly) films. Drug releases of LB- or LH-Gαgly films were evaluated. The drug release profiles of medicated films presented good patterns in both short time and 8 h drug release studies. The permeation study was examined through chick chorioallantoic membrane (CAM) by using modified Franz diffusion cells. Moreover, the irritancy study for buccal films was also examined by a hen’s egg test on CAM model (HET-CAM). The results revealed that LB and LH could permeate through CAM, and these Gαgly films created no irritation on HET-CAM. This indicates that the LB- and LH-Gαgly films are possible to use as buccal films. Keywords: Gelatin, Gelatinized tapioca starch, Buccal film, Chick chorioallantoic membrane

Simple Summary Although zebrafish are used in vast numbers in laboratories all over the world, no consensus has been reached in the scientific community on a humane, consistent, and effective method for euthanasia of this species. Here, we screened commonly used anaesthetic drugs to see if an overdose could induce loss of reflexes of adult zebrafish in a rapid and reliable manner, and without causing distress. The tested anaesthetics were isoeugenol, clove oil, 2-phenoxyethanol, tricaine, benzocaine, lidocaine hydrochloride, and etomidate. We found that lidocaine hydrochloride, buffered with sodium bicarbonate and ethanol to increase its efficacy, induces loss of reflexes in a fast, predictable, and relatively peaceful manner. We recommend its use for adult zebrafish euthanasia. Abstract Zebrafish are often euthanized by overdose of anaesthesia. However, fish may have aversion towards some anaesthetics, and protocol efficacy varies between species. Using wild type adult Danio rerio, we assessed time to loss of opercular beat, righting, and startle reflexes during induction of anaesthetic overdose by either tricaine (0.5 g/L or 1 g/L), benzocaine (1 g/L), 2-phenoxyethanol (3 mL/L), clove oil (0.1%), isoeugenol (540 mg/L), lidocaine hydrochloride (1 g/L), or etomidate (50 mg/L). Initial screening demonstrated that benzocaine and buffered lidocaine hydrochloride achieved the fastest loss of reflexes. The rapid induction times were confirmed when retesting using larger batches of fish. The fastest induction was obtained with 1 g/L lidocaine hydrochloride buffered with 2 g/L NaHCO3, in which all adult zebrafish lost reflexes in less than 2 min. Next, we monitored signs of distress during benzocaine or buffered lidocaine hydrochloride overdose induction. The results indicated that buffered lidocaine hydrochloride caused significantly less aversive behaviors than benzocaine. Finally, we tested several buffers to refine the lidocaine hydrochloride immersion. The most efficient buffer for euthanasia induction using 1g/L lidocaine hydrochloride was 2 g/L NaHCO3 with 50 mL/L 96% ethanol, inducing immobility in less than 10 s and with only 2% of adult zebrafish displaying aversive behaviors during treatment.

This study aimed to develop photo-triggered implantable polymeric microneedles (MNs) for successful drug delivery in a transdermal analgesia system. The prepared iron oxide nanoparticles (Fe3O4NPs)...

In the present study, we developed a simple and rapid analytical method for the quantification of bupivacaine hydrochloride in human biopsy samples of adipose, muscle, neural, connective and cartilage tissue using liquid chromatography-mass spectrometry. Anesthetics were extracted from the tissue samples using 0.1% formic acid in acetonitrile for protein denaturation and hexane for removal of lipophilic impurities. Analytes were separated adequately on Phenomenex Luna Omega polar C18 column using a gradient mobile phase 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The lower limits of quantification were ≤ 97 ng g-1 tissue for all studied tissues. Intra-day recoveries were between 48.2% and 82.1% with relative standard deviations (RSDs) between 1.47% and 14.28%, whereas inter-day recoveries were between 52.2% and 77.6% with RSDs between 2.98% and 14.79%. The calibration curve showed a linear fit with R2 higher than 0.99 in the concentration range from 0.16 to 100 μg g-1 . Lidocaine hydrochloride was tested as internal standard because its recoveries and matrix effects were comparable to bupivacaine hydrochloride. Post-analytical corrections of measured bupivacaine tissue concentrations can accordingly be made based on recovery of lidocaine as internal standard, with recoveries between 51.2% and 86.9% and RSDs between 1.99% and 16.88%. The developed method could be used to study time-dependent spread of bupivacaine locally or to more distant locations across tissue barriers.

The mouth can be affected by important inflammatory processes resulting from localized or systemic diseases such as diabetes, AIDS and leukemia, among others, and are manifested in various types of buccal sores typically presenting pain. This work focuses on the design, formulation, and characterization of four semisolid formulations for oral mucosa in order to symptomatically treat these painful processes. The formulations have two active pharmaceutical ingredients, triamcinolone acetonide (TA) and lidocaine hydrochloride (LIDO). The formula also contains, as an excipient, Orabase®, which is a protective, hydrophobic, and anhydrous adhesive vehicle, used to retain or facilitate the application of active pharmaceutical ingredients to the oral mucosa. After designing the formulations, an analytical method for TA was validated using HPLC so as to achieve reliable analytical results. Franz-type diffusion cells were used to perform drug release studies using synthetic membrane, and permeation studies using buccal mucosa, estimating the amount and rate of TA permeated across the tissue. Additionally, sublingual permeation studies were carried out to evaluate a scenario of a continuous contact of the tongue with the applied formulation. Permeation fluxes and the amount of TA retained within sublingual mucosa were similar to those in buccal mucosa, also implying anti-inflammatory activity in the part of the tongue that is in direct contact with the formulation. In addition, the dynamic conditions of the mouth were recreated in terms of the presence of phosphate buffered saline, constant movement of the tongue, pH, and temperature, using dissolution equipment. The amount of TA released into the phosphate buffered saline in dynamic conditions (subject to being ingested) is well below the normal oral doses of TA, for which the formulation can be considered safe. The formulations applied to buccal or sublingual mucosas under dynamic conditions permit the successful retention of TA within either tissue, where it exerts anti-inflammatory activity. The four formulations studied show a pseudoplastic and thixotropic behavior, ideal for topical application. These results evidence the potential of these topical formulations in the treatment of inflammatory processes in the buccal mucosa.

A new high-performance liquid chromatography (HPLC) method for the simultaneous quantitative determination of active pharmaceutical substances and preservatives in a new dental medication has been developed. The optimization of HPLC method parameters was done through studies of a mobile phase composition and a detection wavelength. Our developing method uses an ACE C18 column (250 × 4.6 mm, 5 µm) and a gradient mode for separation with the acetonitrile and phosphate buffer solution (adjusted to pH 3.0) as mobile phases. The flow rate is 1 ml/ min, and the detection was set at 260 nm (DAD). The method was evaluated according to the ICH guidelines and the State Pharmacopoeia of Ukraine in terms of specificity, accuracy, linearity and precision (repeatability and intermediate precision). The limit of detection and the limit of quantification were also calculated. The developed method was put in place for the analysis of a combined dental gel to a quantitative determination of the APIs (choline salicylate, lidocaine hydrochloride) and preservatives (methylparaben, propylparaben).

This study aimed to improve the transdermal delivery of lidocaine hydrochloride (LidH) using elastic nano-liposomes (ENLs) and microneedle (MN) array pretreatment. LidH-containing ENLs were prepared using soybean phosphatidylcholine and cholesterol, with Span 80 or Tween 80, using a reverse-phase evaporation method. The ENL particle size, stability, and encapsulation efficiency (EE) were characterized and optimized based on the component ratio, pH, and type of surfactant used. In vitro transdermal diffusion study was performed on MN-pretreated mouse skin using Franz diffusion cells. The anesthetic effects of LidH in various formulations after dermal application were evaluated in vivo in rats by measuring the tail withdrawal latency after photothermic stimulation. Stable LidH-loaded Tween 80 or Span 80 ENLs were obtained with particle sizes of 115.8 and 146.6 nm and EEs of 27% and 20%, respectively. The formulations did not exert any cytotoxicity in HaCaT cells. Tween 80 and Span 80 ENL formulations showed enhanced LidH delivery on pretreated mice skin in vitro and prolonged the anesthetic effect in vivo compared to that by LidH application alone. LidH-loaded ENLs applied to MN-pretreated skin can shorten the onset time and prolong the anesthetic effect safely, which merits their further optimization and practical application.

Background: The work presented here is focused on the development of a comprehensive theoretical model for the description of drug release from a double - layer bioresorbable suture thread and the therapeutic efficacy of the active compounds delivered in the surrounding tissue. Methods: In particular, the system under investigation is composed of a core of slow-degrading polylactic- acid-co-ε-caprolactone (PLCL), where an antibiotic compound (Vancomycin) is loaded, surrounded by a shell of a fast-degrading polylactic-co-glycolic acid (PLGA) which contains an anesthetic drug (Lidocaine hydrochloride) for the post-surgical pain relief. Results: This system is of potential interest for the combined effects provided by the different active molecules, but the different release and polymer degradation dynamics, as well as their mutual influence, do not allow an intuitive a priori evaluation of device behavior, which can be rationalized through mathematical modeling. The model takes into account the main involved phenomena (polymer degradation and diffusion of the drugs within the device and the tissue, where they are metabolized) and their synergic effects on the overall system behavior. Conclusion: Model results are discussed in order to quantify the impact of the main design parameters on device performances, thanks to the use of phase diagrams (which show drug effect in time and space) whose insights are summarized in order to determine a design space according to the specific needs.

It is the first time to develop electrochemiluminescence resonance energy transfer (ECRET) strategy using luminol-doped silica nanoparticles (luminol-SiNPs) for both “turn-off” detection of 2,4,6-trinitrophenol (TNP) and “turn-on” detection of anesthetic drug lidocaine hydrochloride (LDC). The spectral overlap of ECL emission of luminol-SiNPs with the absorption of TNP triggers ECRET from luminol-SiNPs to TNP and results in the decreased ECL signals. Besides, the specific interaction between TNP and LDC consumes TNP, accordingly prevents ECRET from luminol-SiNPs to TNP and achieves increasing ECL signals. The proposed ECRET strategy using luminol-SiNPs exhibits fast response (within 10 min), high sensitivity with LOD of 22.4 nM for TNP and 92.5 nM for LDC, respectively. It is also successfully applied in ECRET detection of TNP in lake water, LDC in human serum and commercial drug sample detections with satisfactory recoveries. More importantly, ECL of luminol-SiNPs is measured via linear sweep voltammetry by electrochemical reduction of dissolved oxygen at negative potential (– 1 V) and in no need of adding hydrogen peroxide (H2O2). Reactive oxygen species be generated in situ and make luminol-SiNPs system emit ECL, which makes ECL of the whole luminol-SiNPs system more stable than luminol-H2O2 system.

Introduction: To investigate the effect of resultant precipitate formed on interaction between 2% lidocaine hydrochloride with adrenaline (LA) and 2.5% sodium hypochlorite (NaOCl) on root canal dentin before and after chemomechanical preparation, using scanning electron microscopy (SEM). Methods: Sixty mandibular premolars were decoronated, and the root length was standardized. All specimens were randomly distributed into the following three groups: Group I (control): 2% LA mixed with sterile water without root canal instrumentation, Group II: 2% LA with 2.5% NaOCl and no instrumentation, and Group III: 2% LA with 2.5% NaOCl, followed by mechanical instrumentation with rotary files. Teeth samples were sectioned into three parts, split and SEM analysis of the root canal wall was done at cervical, middle, and apical root thirds. Results: SEM images revealed patent dentinal tubules with no precipitate occlusion in the control group, whereas there was occlusion of dentinal tubules with a precipitate in all the specimens in Group II and Group III at all the three root levels studied. Conclusions: The precipitate formed on the interaction between 2% LA solution and 2.5% NaOCl tends to occlude the dentinal tubules at the coronal, middle, and apical root thirds. The chemomechanical rotary instrumentation procedure did not effectively remove the precipitate from all the three levels of the root specimens studied. LA/sterile water group did not result in any precipitate formation on root canal dentin.

We report the lowest energy conformers obtained by a conformational search for protonated lidocaine, mepivacaine and bupivacaine in the gas phase at the B3LYP/cc-pVTZ level of theory, and examine the effect of aqueous solvation on the energetics using the COSMO continuous solvent model. We also look at the effect of microhydration by crystallization water molecules on the relative energies of the conformers. We found that water molecules and chloride ion stabilize conformers by hydrogen bonding. We report a revised structure for the conformer present in solution for lidocaine hydrochloride.

Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize the experimental setup. However, there is no consensus on these methods. In transdermal studies, barrier integrity has been evaluated by measuring electrical resistance (ER) across the skin, which has been demonstrated to be a simple, fast, safe, and cost-effective method. Therefore, the aims here were to investigate whether ER might also be an effective method to evaluate buccal and esophageal epithelium mucosa integrity for in vitro permeation studies, and to establish a cut-off ER value for each epithelium mucosa model. We further investigated whether buccal epithelium could be substituted by esophageal epithelium in transbuccal permeation studies, and whether their permeability and integrity were affected by freezing at −20 °C for 3 weeks. Fresh and frozen swine buccal and esophageal epithelia were mounted in Franz diffusion cells and were then submitted to ER measurement. Permeation assays were performed using lidocaine hydrochloride as a hydrophilic drug model. ER was shown to be a reliable method for evaluating esophageal and buccal epithelia. The esophageal epithelium presented higher permeability compared to the buccal epithelium. For both epithelia, freezing and storage led to decreased electrical resistivity and increased permeability. We conclude that ER may be safely used to confirm tissue integrity when it is equal to or above 3 kΩ for fresh esophageal mucosa, but not for buccal epithelium mucosa. However, the use of esophageal epithelium in in vitro transmucosal studies could overestimate the absorption of hydrophilic drugs. In addition, fresh samples are recommended for these experiments, especially when hydrophilic drugs are involved.

The main purpose of this study was to assess a lidocaine hydrochloride-loaded chitosan-pectin-hyaluronic polyelectrolyte complex for rapid onset and sustained release in dry socket wound treatment. Nine formulations (LCs) of lidocaine hydrochloride (LH) loaded into a chitosan–pectin–hyaluronic polyelectrolyte complex (PEC) were assessed using full factorial design (two factors × three levels). The formulations ranged between 4 and 10% w/w LH and 0.5–1.5% w/w HA. The following physicochemical properties of LCs were characterized: size, zeta potential, % entrapment efficiency, viscosity, mucoadhesiveness, % drug release, morphology, storage stability, and cytotoxicity. The particle size, zeta potential, % EE, viscosity, and % mucoadhesion increased with increasing LH and HA concentrations. Rapid release of LH followed a zero-order model, and a steady-state percentage of the drug was released over 4 h. LCs were found to be non-cytotoxic compared to LH solution. LH loaded into PEC demonstrated appropriate characteristics—including suitable rate of release—and fit a zero-order model. Furthermore, it was not cytotoxic and showed good stability in a high-HA formula, making it a promising candidate for future topical oral formulations.

The mouth can be affected by important inflammatory processes resulting from localized or systemic diseases, such as diabetes, AIDS, and leukemia, among others, which are manifested in various types of buccal sores, typically presenting pain [1]. The present work focuses on the design, formulation, and characterization of four semi-solid formulations for oral mucosa in order to symptomatically treat these painful processes. The formulations have two active pharmaceutical ingredients: triamcinolone acetonide (TA) and lidocaine hydrochloride (LIDO). The formulations also contain Orabase® as an excipient, which is a protective, hydrophobic, and anhydrous adhesive vehicle, used to retain or facilitate the application of active pharmaceutical ingredients (APIs) to the oral mucosa. After designing the formulations, the validation of the analytical method was performed to achieve reliable analytical results. Franz-type diffusion cells were used to perform drug release studies using synthetic membrane, and permeation studies using buccal mucosa, permitting the estimation of the amount and rate of TA permeated across this mucous membrane. Further, the amount of TA retained within the tissue was estimated, as this is where it performs its anti-inflammatory activity, and showed no significant differences between the 0.05% TA + LIDO and 0.1% TA + LIDO formulations (p > 0.05). Therefore, the results demonstrate the suitability of the administration of the lowest concentration of TA tested, which achieved a similar efficacy as higher concentrations and reduced the potential systemic effects of corticoid administration. Furthermore, sublingual permeation studies were carried out to evaluate a scenario of continuous contact of the tongue with the applied formulation. The four formulations studied show pseudoplastic and thixotropic behavior, ideal for topical application. These results provide evidence for the potential of these topical formulations for the treatment of inflammatory processes in the buccal mucosa. Keywords: triamcinolone acetonide; buccal administration; semisolid formulations; thixotropic behavior; lidocaine hydrochloride; Franz-type diffusion cells

Aim: Anxiety and intolerance to dental local anesthetic injections are common in patients undergoing dental procedures. This work was designed to study cytotoxicity of selected flavors in primary gingival keratinocytes (PGK), to acquire information on their suitability for use in dental lidocaine hydrochloride (LID) injection. We also evaluated the bio-mimetic taste of LID dental injection in the presence of selected flavors and sweetener using an Astree electronic tongue (ETongue). Methods: The cytotoxicity of chocolate natural and artificial flavor (CTE), raspberry flavor artificial (RAS), cherry flavor (CHR), bitterness suppressor flavor (BSF) and lemon flavor extract (LFE) at various dilutions (0.16&ndash, 10% v/v) was carried out in PGK using the live cell morphological analysis and MTT cell cytotoxicity assay. Based on the cytotoxicity data, CTE and RAS were added to Xylocaine&reg, (2%) along with 0.09% sodium saccharin and taste was assessed using an ETongue. Results: After three hours of treatment, a dose-dependent cell death was induced by all flavors compared to the untreated control. BSF was found to be more toxic when compared to other flavors. CTE was found to be less toxic. The mean IC50 values of CTE, RAS, CHR, BSF and LFE in PGK were found to be 9.54, 8.43, 2.21, 0.38 and 4.01 mg/mL. Taste analysis with the ETongue showed a clear taste difference between the control and test formulations containing CTE and RAS flavors along with sodium saccharin. Conclusion: CTE and RAS flavors in combination with 0.09% sodium saccharin can achieve a significant taste-masking effect in the dental LID injection.

The delivery of bioactive agents using active wound dressings for the management of pain and infections offers improved performances in the treatment of wound complications. In this work, solid lipid microparticles (SLMPs) loaded with lidocaine hydrochloride (LID) were processed and the formulation was evaluated regarding its ability to deliver the drug at the wound site and through the skin barrier. The SLMPs of glyceryl monostearate (GMS) were prepared with different LID contents (0, 1, 2, 4, and 10 wt.%) using the solvent-free and one-step PGSS (Particles from Gas-Saturated Solutions) technique. PGSS exploits the use of supercritical CO2 (scCO2) as a plasticizer for lipids and as pressurizing agent for the atomization of particles. The SLMPs were characterized in terms of shape, size, and morphology (SEM), physicochemical properties (ATR-IR, XRD), and drug content and release behavior. An in vitro test for the evaluation of the influence of the wound environment on the LID release rate from SLMPs was studied using different bioengineered human skin substitutes obtained by 3D-bioprinting. Finally, the antimicrobial activity of the SLMPs was evaluated against three relevant bacteria in wound infections (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). SLMPs processed with 10 wt.% of LID showed a remarkable performance to provide effective doses for pain relief and preventive infection effects This research was funded by Xunta de Galicia [ED431F 2016/010], MCIUN [RTI2018-094131-A-I00], Agrupación Estratégica de Materiales [AeMAT-BIOMEDCO2, ED431E 2018/08], Agencia Estatal de Investigación [AEI] and FEDER funds. C.A.G.-G. acknowledges to MINECO for a Ramón y Cajal Fellowship [RYC2014-15239]. This work was partially supported by Programa de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid [S2018/BAA-4480, Biopieltec-CM], Programa Estatal de I+D+I Orientada a los Retos de la Sociedad [RTI2018-101627-B-I00] and Cátedra Fundación Ramón Areces SI

In the area of developing oromucosal drug delivery systems, mucoadhesive buccal films are the most promising formulations for either systemic or local drug delivery. The current study presents the fabrication of buccal films, by combining fused deposition modeling (FDM) and inkjet printing. Hydroxypropyl methylcellulose-based films were fabricated via FDM, containing the non-steroidal anti-inflammatory drug ketoprofen. Unidirectional release properties were achieved, by incorporating an ethyl cellulose-based backing layer. The local anesthetic lidocaine hydrochloride, combined with the permeation enhancer l-menthol, was deposited onto the film by inkjet printing. Physicochemical analysis showed alterations in the characteristics of the films, and the mucoadhesive and mechanical properties were effectively modified, due to the ink deposition on the substrates. The in vitro release data of the active pharmaceutical compounds, as well as the permeation profiles across ex vivo porcine buccal mucosa and filter-grown TR146 cells of human buccal origin, were associated with the presence of the permeation enhancer and the backing layer. The lack of any toxicity of the fabricated films was demonstrated by the MTT viability assay. This proof-of-concept study provides an alternative formulation approach of mucoadhesive buccal films, intended for the treatment of local oromucosal diseases or systemic drug delivery.

Background and importance Undergoing small surgeries, aesthetic procedures or needle injections can be stressful, especially for paediatric patients. Various local anaesthetics have therefore been developed to numb the skin, including commercially available medications. Unfortunately, shortage of medicines, including for local anaesthesia, remains a widespread and persistent problem. LETS GEL KIT is a ready to use kit developed by Fagron to compound a topical anaesthetic gel. LETS GEL KIT contains lidocaine hydrochloride (4% w/w), epinephrine bitartrate (0.18% w/w), tetracaine hydrochloride (0.5% w/w) and sodium metabisulfite (0.075% w/w). LETS has been shown to be equivalent in providing and maintaining anaesthesia in the treatment of facial lacerations, with up to 10-fold less systemic exposure, compared with a 2.5% lidocaine/2.5% prilocaine solution. Aim and objectives To evaluate the chemical stability of the LETS GEL KIT when stored in syringes. Material and methods Samples were stored in plastic syringes (Comar, USA) under controlled refrigeration (2–8°C) and controlled room temperature (20–25°C). Stability was assessed by examining colour, odour and pH, and by measuring the active content at varying time points (0, 30, 60, 90, 120 and 150 days) over a 150 day period. API quantification was performed by validated high performance liquid chromatography (HPLC-UV). Results Throughout the whole study, no phenomena, such as turbidity, macroscopically visible crystal growth or phase separation, were observed. Colour, odour and pH showed no significant change. Drug content (%) after 150 days were (for refrigerated and room temperature, respectively): lidocaine hydrochloride 94.47±0.25 and 94.86±0.70; epinephrine bitartrate 97.90±0.33 and 98.82±0.20; and tetracaine hydrochloride 102.09±0.70 and 102.18±1.15. Conclusion and relevance In the current study, LETS GEL KIT showed excellent stability under both controlled refrigerated conditions (2–8°C) and at room temperature (15–25°C) for up to 150 days. Therefore, prefilled compounded syringes using LETS GEL KIT can be a valuable alternative when commercial medication is not suitable or available. References and/or acknowledgements Conflict of interest Corporate sponsored research or other substantive relationships: The study was sponsored by Fagron BV.

Buccal delivery is considered the most suitable, easy, and safest route of administration. So it can be used as an alternative route to the peroral route for the systemic administration of drugs. Oral films (OFs) are used as a unique approach, because it dissolves quickly in the mouth and directly reaches to the systemic circulation. The aim of this study is to formulate and evaluate OF of an anaethetic drug lidocaine (LH) and improve its local effect. Oral films were prepared by using chitosan and polyvinylpyrolidone. OFs were assessed for compatibility studies, surface pH, swelling properties, In-Vitro bioadhesion, mechanical properties, disintegration time, dissolution time and in- vitro drug release. It was found that actual LH content in the prepared patch was in the range of 95-105% of the claimed content. The addition of propylene glycol as a plasticizer gave good mechanical properties in concentration of 40%. The prepared oral films swelled and reached an Equilibrium state of swelling. The prepared polymeric films showed good adhesion and acceptable pH. It could be concluded that the release of LH is higher from films contain 1% chitosan. Increasing chitosan concentration to 2% resulted in decreasing the initial dissolution rate. The combination of chitosan (2%) , PVP(10%) and PG at 40% w/w gave a reasonable LH release.

Chitosan/collagen composite scaffolds encapsulating allantoin and lidocaine hydrochloride were formulated in various ratios and characterized in vitro for their applications in wound healing. After fabrication, scaffolds were characterized in terms of topographical properties, surface roughness, and swelling behavior, and then their stabilities were monitored by hydrolytic and enzymatic degradation studies. Following compatibility studies among the active ingredients, drugs were encapsulated within scaffolds, and encapsulation efficiency and drug release studies were carried. Finally, in vitro cell viability and scratch wound healing assays were carried to assess scaffolds as wound dressings. Results suggest that blending of polymers with drugs changed topographical properties and surface roughness prominently. It is found that the formulation with chitosan/collagen ratio of 70/30 is more resistant to both hydrolytic and enzymatic degradation routes due to having favored properties of both collagen and chitosan. In vitro drug release studies indicated rapid release of drugs, hence the scaffolds could be advantageous for patients that need an immediate anesthetic effect in wound healing therapy. The cell culture studies demonstrated that the chitosan/collagen composite scaffolds showed no toxicity, and cell migrations were increased depending on the collagen ratio in scaffolds. These results suggest that chitosan/collagen scaffolds combined with allantoin and lidocaine hydrochloride could be a promising candidate for wound healing applications. Marmara University Scientific Research Projects Coordination UnitMarmara University [SAG-CYLP-070317-0091] This work has been supported by Marmara University Scientific Research Projects Coordination Unit under Grant [number SAG-CYLP-070317-0091]. WOS:000524010200001 Q2

The aim of this study was to develop and characterize a double layer biomembrane for dual drug delivery to be used for the treatment of wounds. The membrane was composed of chitosan, hydroxypropyl methylcellulose and lidocaine chloride (anesthetic drug) in the first layer, and of sodium alginate-polymyxin B sulphate (antibiotic) nanoparticles as the second layer. A product with excellent thickness (0.01-0.02 mm), adequate mechanical properties with respect to elasticity, stiffness, tension, and compatible pH for lesion application has been successfully obtained. The incorporation of the drugs was confirmed analysing the membrane cross-sections by scanning electron microscopy. A strong interaction between the drugs and the functional groups of respective polymers was confirmed by Fourier-Transform Infrared Spectroscopy, thermal analysis and X-ray diffraction. Microbiological assays showed a high antimicrobial activity when polymyxin B was present to act against the Staphylococcus aureus and Pseudomonas aeruginosa strains. Low cytotoxicity observed in a cell viability colorimetric assay and SEM analysis suggest biocompatibility between the developed biomembrane and the cell culture. The in vivo assay allowed visualizing the healing potential by calculating the wound retraction index and by histological analysis. Our results confirm the effectiveness of the developed innovative biomaterial for tissue repair and regeneration in an animal model., The authors acknowledge the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil), Fundação de Amparo a Pesquisa do Estado de Sergipe (FAPITEC, MS/CNPq/FAPITEC/SE/SES N◦06/2018) e do Conselho Nacional de Pesquisas (CNPq, Apoio a Projetos de Pesquisa/MCTI/CNPQ/Universal 14/2014) for supporting funds. EBS acknowledges the Portuguese Science and Technology Foundation (FCT) for the funded projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund) financed from national funds, and co-financed Education (FCT/MEC) from national funds and FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Background Effective postoperative pain control is essential for the recovery of surgical patients. However, long-term analgesia can seldom be achieved with the existing medications. The injectable implants prepared by biodegradable polyesters can be conveniently used during the surgery and slowly release analgesics near the operative incision for a long period. Method In this study, we prepared lidocaine hydrochloride (Lido-HCl)-loaded injectable poly(lacticco- glycolic acid) (PLGA) implants for prolonged analgesia. The optimized formulation of this injectable implant sustained drug release for up to 5 days, with a cumulative release of 85.8%±1.9% in the in vitro release experiment. Results The in vivo release of the implants in rats showed good consistency with the in vitro release. The pharmacokinetics of Lido-HCl implants in the thigh muscle of rats was evaluated, and the AUC0-120 h of the Lido-HCl implant was 11.4 times that of Lido-HCl solution, indicating a good sustained release function of the implant. The pharmacodynamics of Lido-HCl implants was measured by the hot plate test. The Lido-HCl solution blocked the sciatic nerve of rats for less than 4 h, while the Lido-HCl implant efficiently blocked the nerve for approximately 120 h. Conclusion These results demonstrated that the PLGA-based injectable implant is a suitable carrier for postoperative pain control.

The objective of this work was to measure and correlate the solubility of lidocaine hydrochloride in eight pure solvents, including ethanol, n-propanol, isopropanol, n-butanol, isobutanol, acetone, methyl acetate, water, and binary mixtures at (291.15 to 331.15) K by using gravimetric method under atmospheric pressure. The results reveal that the solubility of lidocaine hydrochloride increases with increasing temperature in all solvent selected. The modified Apelblat equation, van’t Hoff equation, λh equation, Wilson model and NRTL model were successfully used to correlate the experimental solubility in pure solvents and binary solvent mixtures. In addition, the thermodynamic properties of dissolution of Lidocaine hydrochloride such as Gibbs energy (∆G°sol), molar enthalpy of dissolution (∆H°sol), and molar entropy of dissolution (∆S°sol ) were calculated. Consequently, the experimental solubility and correlation equations can be used as essential data and simulation models in the purification and separation of lidocaine hydrochloride.

The technique of the qualitative and quantitative determination of active substances – decamethoxine and lidocaine hydrochloride in a new combination drug for preventing and treating inflammatory diseases of the oral cavity was developed.The aim of the work was to develop a methodology to identify and determine the active pharmaceutical ingredient in the composition of the dental gel.The objects were specimens of the developed dental gel containing lidocaine hydrochloride and decamethoxine. The study was conducted using high performance liquid chromatography (HPLC).The conditions for HPLC chromatographic investigations, providing sufficient selectivity and separation efficiency of the gel components were proposed.It was determined that the content of the dental gel component is within acceptable limits, and metrological characteristics of the method allow to recommend it to control the gel quality. 1 gram of the gel contains: decamethoxine – 0.591 mg/g (at a rate of 0.45–0.55 mg/g), lidocaine hydrochloride – 0.396 mg/g (at a rate of 0.36–0.44 mg/g).Approximate retention time of decamethoxine peak is 18.4 min, lidocaine hydrochloride – 13.5 min. Retention time of the peak of decamethoxine and lidocaine hydrochloride investigational solution and reference solution did not exceed 2%.

This study examines the preparation of sustained-release lidocaine polyelectrolyte complex using reactive melt extrusion. Eudragit L100-55 was selected as the ionic polymer. The influence of drug forms (freebase vs. hydrochloride salt) on lidocaine-Eudragit L100-55 interactions, physical stability, and dissolution properties of extrudates was investigated. It was confirmed by DSC, FT-IR and Raman spectroscopy that polyelectrolyte could only form via the acid-base reaction between Eudragit L100-55 and lidocaine freebase. Due to this ionic interaction, the lidocaine extrudate was physically more stable than the lidocaine hydrochloride extrudate during the storage under stressed condition. Drug release from lidocaine extrudate was a function of drug solubility, polymer solubility, drug-polymer interaction, and drug-induced microenvironment pH. At 30% drug loading, extrudate exhibited sustained release in aqueous media at pH 1.2 and 4.5. Due to the alkaline microenvironment pH induced by dissolved lidocaine, Eudragit L100-55 was solubilized and sustained-release was not achieved in water and aqueous media at pH 5.5. In comparison, lidocaine hydrochloride induced an acidic microenvironment. Drug release of lidocaine hydrochloride extrudate was similar at pH 1.2, 4.5, 5.5 and water with drug being released over 10 h. The release of lidocaine hydrochloride from the extrudates in these media was primarily controlled by microenvironment pH. It is concluded that different forms of lidocaine resulted in different drug-polymer interactions and distinctive physicochemical properties of extrudates.

We report a type of dissolving microneedles (DMNs) which was made of composite matrix materials of hydroxypropyl methyl cellulose (HPMC) and poly(methylvinylether‑co‑maleic anhydride) (PMVE/MA copolymer, Gantrez S-97), and was successfully loaded with lidocaine hydrochloride. The weight of lidocaine hydrochloride loaded in the microneedles tip was 70% of the weight of the whole tip. The content was 3.43 ± 0.12 mg in weight, which was determined by high performance liquid chromatography (HPLC). The results for mechanical test showed that these microneedles were able to penetrate into the skin of the experimental animals, that was proved using organic staining, texture analyzer and histological examination. The fracture force of the microneedles was 5.442 ± 0.412 N, which was much higher than the one required for the skin penetration. The DMNs with lidocaine hydrochloride could be dissolved inside of the rat skin in 5 min. The onset time would be faster (in5 min) when it was applied to the guinea pig model, in comparing with a commercially available anesthesia cream that had an onset time for 100 min. However, the efficacy of the DMNs for the local anesthesia only lasted for 16 min. It was shorter than that of the commercially available anesthesia cream with which the efficacy could last for about 130 min. After the DMNs was packaged under the vacuum and dark condition, it was stable for 3 months under the condition of a temperature of 40 ± 2 °C and a humidity of 75 ± 5%. The result of the experiment for the safety evaluation showed that the microneedles were non-irritating and non-allergenic to the skin. In conclusion, the DMNs with lidocaine hydrochloride could be safely administered to the skin with a quick onset time for the local anesthesia.

In this research, topical lidocaine solution for ocular administration was assessed for biocompatibility as a non-invasive anesthetic drug delivery. The study aimed to investigate the cytotoxicity against human corneal epithelial cells (HCECs) and to evaluate drug permeation. In the case of cytotoxicity, HCECs were treated with drug solution, analyzed for percent viability. For permeation study, the modified-franz diffusion method was used to study permeation partition coefficient of lidocaine solution; moreover, the drug retained on the sclera was also determined. HCECs were treated with lidocaine solutions with the concentration range of 0.781 -100 g/L. Significantly decrease in cell viability with the concentration above 12 g/L was detected by Resazurin metabolic rate assay. The permeation coefficient of lidocaine hydrochloride solution could not be determined because of drug absence in the receptor chamber. The entire drug loaded remained in the donor chamber and adsorbed on the surface of sclera tissue. The results suggested that topical lidocaine solution showed reasonably safe and lidocaine drops did not absorbed through the sclera. In present study, local topical anesthetic delivery of lidocaine was considered safe for ophthalmologic treatment.