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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.

The problem of drug delivery often concentrates on the prolongation of drug activity. Application of natural polymers which are biodegradable and inexpensive is in the interest of many researchers. The aim of this study was the application of newly synthesized starch derivatives as potential functional excipients proposed for hydrophilic gel with lidocaine hydrochloride (LH) to prolong drug release from the hydrogel matrix. In our study, we investigated the effect of starch modified with citric acid on the release kinetics of LH using UV-VIS and Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), as well as viscosity and pH measurements. We demonstrated the effectiveness of citric-acid-modified starch in prolonging the release of LH from methylcellulose gel.

© 2022, The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated. Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisone acetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80, was best for its highest antifungal film activity (20.00 ± 0.07 mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections. Graphical Abstract: [Figure not available: see fulltext.]

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.

Topical delivery of local anaesthetic drugs such as Lidocaine HCl using carriers and novel nanotechnology can enhance effective drug permeation through the skin into deeper layers and exhibit desirable duration of action. The present study was aimed to formulate and evaluate Lidocaine HCl loaded cubosomes (LHLCs) for sustained therapeutic topical action. Cubosomes emanated as favourable means for the delivery of the drug. LHLCs were prepared by top-down technique using lipid and polymer. Eight formulations of LHLCs were prepared using different concentrations of glyceryl monooleate (GMO) and Poloxamer 407 (P-407). Local anaesthetics create loss of sensation in particular region of the body by inhibiting impulse generation and propagation. Lidocaine HCl is most commonly used amino amide local anaesthetic. It is used as local, topical, intravenous, epidural, peripheral and spinal anaesthesia. The prepared cubosomal dispersions were evaluated to determine surface morphology, particle size, poly dispersibility index (PDI), zeta potential, entrapment ability, tissue distribution studies, and in vitro drug release studies. Scanning Electron Microscopic analysis confirmed that drug was encapsulated in bicontinuous structure. The maximum entrapment efficiency was found to be 89.85±1.1% with vesicle size as 228±2.1nm, charge as -5.68±2.7, PDI as 0.295 and 98.83%± 0.12 in vitro drug release at the end of 12 hr for F7 formulation, which was confirmed as optimized cubosomal dispersion.

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).

Li-Zhou Wang,1,&ast; Xiao-Xia Hu,2,&ast; Xiang-Chun Shen,2,3 Tian-Cheng Wang,4 Shi Zhou1 1Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2The State Laboratory of Functions and Application of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 4Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Cheng WangDepartment of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86 15073190153Email 421176806@qq.comShi ZhouDepartment of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of ChinaTel +86 13809477708Email zhoushi@gmc.edu.cnObjective: To investigate the sustained release of lidocaine from a lidocaine–epirubicin–lipiodol emulsion created by water-in-oil (W/O) technique in vivo and evaluate the efficacy and safety of intraarterial lidocaine administration for intra- and postoperative pain control in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods: The in vivo concentrations of lidocaine were determined in tumor tissues after VX2 rabbit models for hepatic tumor were administered with intra-arterial lidocaine–epirubicin–lipiodol emulsion. A prospective randomized controlled clinical trial was performed, enrolling 70 consecutive patients who underwent TACE. Patients were randomized into two groups: Group A received an immediate bolus intraarterial lidocaine injection before TACE, and Group B received a lidocaine–epirubicin–lipiodol emulsion during TACE. Pain intensity was compared between the two groups using a visual analog scale (VAS) score before (Tbefore) and at 0 h (T0), 4 h (T4), 8 h (T8), 24 h (T24), 48 h (T48), and 72 h (T72) after the procedure. Adverse events and intake of analgesics were evaluated and compared between the two groups.Results: The concentrations of lidocaine in tumor tissues were higher in experimental group than in control group at T0.5 (P=0.004), T1 (P=0.038), T4 (P=0.036), and T8 (P=0.029). In the clinical trial, VAS scores in Group B were significantly lower than in Group A at T0 (P=0.006), T4 (P=0.001), T8 (P=0.002), and T24 (P=0.005). The tramadol intake in Group B was significantly lower than in Group A (P=0.021). No significant difference was observed regarding the incidence of adverse events between the two groups.Conclusion: This study demonstrated the effectiveness and safety of intraarterial lidocaine administration using the W/O technique in controlling intra- and post-TACE pain.Keywords: carcinoma, hepatocellular, chemoembolization, therapeutic, lidocaine hydrochloride, pain management

Various anaesthetic agents have been used in dentistry for the extraction of teeth. The most commonly used local anaesthetic agent is lidocaine hydrochloride. Recently, articaine hydrochloride came into existence because of its versatile properties and longer duration of action. Due to lack of study of effects of articaine on various systems, the present study is aimed to compare the anaesthetic efficacy of articaine and lidocaine with adrenaline during the extraction of mandibular molars. A total of 100 patients was randomly divided into two groups (50 each) and clinical variables such onset and duration of anaesthesia, blood pressure, oxygen saturation, pulse rate, and pain perception were recorded at different time intervals using a visual analogue scale. The statistical analysis was performed using SPSS version 22.0. Mean and standard deviations, frequency distribution analysis, and the chi squared test were performed to calculate variables and a p0.05 was considered significant. Statistically significant differences were obtained regarding mean time of onset of anaesthesia (p0.001), mean duration of the anaesthetic effect (p0.001), and pain perception for the articaine group. No significant results were obtained for blood pressure, oxygen saturation, or pulse rate. During the deposition of articaine, patients reported less pain than with lidocaine. Articaine hydrochloride helped to achieve increased anaesthetic success in dental applications over lidocaine hydrochloride in terms of fast time of onset, longer duration, and less pain, all of which were attributed to its greater diffusion properties.

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.

Background High-intensity ultrasound has been used to induce acoustic cavitation in the skin and subsequently enhances skin permeability to deliver hydrophobic topical medications including lidocaine. In contrast, instead of changing skin permeability, pulsed application of low-intensity focused ultrasound (FUS) has shown to non-invasively and temporarily disrupt drug-plasma protein binding, thus has potential to enhance the anesthetic effects of hydrophilic lidocaine hydrochloride through unbinding it from serum/interstitial α1-acid glycoprotein (AAG). Methods FUS, operating at fundamental frequency of 500 kHz, was applied pulse-mode (55-ms pulse duration, 4-Hz pulse repetition frequency) at a spatial-peak pulse-average intensity of 5 W/cm2. In vitro equilibrium dialysis was performed to measure the unbound concentration of lidocaine (lidocaine hydrochloride) from dialysis cassettes, one located at the sonication focus and the other outside the sonication path, all immersed in phosphate-buffered saline solution containing both lidocaine (10 µg/mL) and human AAG (5 mg/mL). In subsequent animal experiments (Sprague-Dawley rats, n = 10), somatosensory evoked potential (SSEP), elicited by electrical stimulations to the unilateral hind leg, was measured under three experimental conditions—applications of FUS to the unilateral thigh area at the site of administered topical lidocaine, FUS only, and lidocaine only. Skin temperature was measured before and after sonication. Passive cavitation detection was also performed during sonication to evaluate the presence of FUS-induced cavitation. Results Sonication increased the unbound lidocaine concentration (8.7 ± 3.3 %) from the dialysis cassette, compared to that measured outside the sonication path (P F(2,27) = 3.2 − 4.0, P Conclusions Unbinding lidocaine from the plasma proteins by exposure to non-thermal low-intensity ultrasound is attributed as the main mechanism behind the observation.

Darbo tikslas: sumodeliuoti polimerinę plėvelę su lidokaino hidrochloridu dengimui ant mikroadatų, siekiant veiksmingos lidokaino hidrochlorido skvarbos į odą. Darbo objektas: polimerinėmis plėvelėmis dengtos mikroadatos. Darbo aktualumas: tradiciniai lidokaino hidrochlorido patekimo į organizmą injekcijomis būdai sukelia skausmą pacientams, mechaniškai pažeidžia audinius, atsiranda mikrobinės infekcijos rizika. Polimerinėmis plėvelėmis dengtų mikroadatų panaudojimas yra vertinamas, kaip racionali alternatyva injekcijoms bei priemonė pasiekti veiksmingą vaistinių medžiagų tiekimą į odą, todėl tokie tyrimai laikomi aktualiais. Metodai: polimerinių plėvelių gamyba liejimo metodu; fizikinių – cheminių, mechaninių savybių įvertinimas (masės, storio, tirpumo, pH, likutinės drėgmės, lipnumo, plyšimo jėgos ir atstumo iki plyšimo); lidokaino hidrochlorido skvarbos nustatymas ultra efektyviosios skysčių chromatografijos metodu. Darbo uždaviniai: suformuoti polimerinę plėvelę iš polivinilo alkoholio, karboksimetilceliuliozės natrio druskos ir plastifikatoriaus; ištirti polimerinių plėvelių fizikines – chemines ir mechanines savybes su lidokaino hidrochloridu ir atrinkti tinkamiausią mikroadatų padengimui; įvertinti skirtingų mikroadatų poveikį lidokaino hidrochlorido skvarbai į odą (ex vivo) iš polimerinių tirpalų; nustatyti lidokaino hidrochlorido skvarbą į odą (ex vivo) panaudojus polimerinėmis plėvelėmis dengtas mikroadatas. Darbo rezultatai: suformuota polimerinė plėvelė iš polivinilo alkoholio ir karboksimetilceliuliozės natrio druskos 1:3 santykiu, su propilenglikoliu 1:20 santykiu. Į atsirinktas polimerines plėveles buvo įterpta skirtingų koncentracijų 5 %, 7 %, 10 % lidokaino hidrochlorido ir ištirtos polimerinių plėvelių fizikinės – cheminės ir mechaninės savybės. Polimerinių plėvelių masė nuo 0,135-0,142 g, storis 154,200–161,800 µm, tirpumas 5,170–5,375 min, likutinė drėgmė 6,118–6,626 %, pH reikšmė 6,397 6,521,viršutinis lipnumas nuo 0,614–0,856 N, apatinis nuo 0,590–0,956 N, plyšimo jėga 7,259–8,105 N, atstumas iki plyšimo 7,922–8,317 mm. Po šių savybių ištyrimo pasirinkta polimerinė plėvelė su 10 % lidokaino hidrochloridu pagal didžiausią viršutinį (0,856 N) ir apatinį (0,956 N) lipnumą,likutinę drėgmę (6,626 %), plyšimo jėgą (8,105 N), atstumą iki plyšimo (8,317 mm). Didžiausia lidokaino hidrochlorido skvarba iš polimerinių tirpalų, panaudojus 800 µm ilgio ir 200 µm pločio ir 600 µm ilgio ir 200 µm pločio mikroadatas. Mažiausia lidokaino hidrochlorido skvarba panaudojus,400 µm ilgio ir 200 µm pločio mikroadatas. Didžiausia lidokaino hidrochlorido skvarba į odą,panaudojus polimerinėmis plėvelėmis dengtas 600 µm ilgio ir 200 µm pločio mikroadatas. Mažiausia lidokaino hidrochlorido skvarba į odą, panaudojus 800 µm ilgio ir 200 µm pločio polimerinėmis plėvelėmis dengtas mikroadatas. Išvados: suformuota polimerinė plėvelė iš polivinilo alkoholio ir karbosimetilceliuliozės natrio druskos su propilenglikoliu pasižymėjo tinkamomis savybėmis, kad būtų galima įterpti modelinę vaistinę medžiagą – lidokaino hidrochloridą. Į polimerines plėveles įterpus skirtingus lidokaino hidrochlorido kiekius ir ištyrus fizikines – chemines savybes, polimerinių plėvelių savybės pasikeitė. Įvertinus lipnumą, drėgmę, plyšimo jėgą, atstumą iki plyšimo, pasirinkta polimerinė plėvelė su 10 % lidokaino hidrochloridu. Didžiausia lidokaino hidrochlorido skvarba į odą (ex vivo) iš polimerinių tirpalų panaudojus 800 µm ilgio ir 400 µm pločio bei 600 µm ilgio ir 200 µm mikroadatas. Mažiausia lidokaino hidrochlorido skvarba iš pažeistos odos panaudojus 400µm ilgio ir 200 µm pločio mikroadatas. Įvertinus lidokaino hidrochlorido rezultatus, dengti polimerinėmis plėvelėmis pasirinktos 800 ilgio ir 400 µm pločio bei 600 µm ilgio ir 200 µm pločio mikroadatos. Vaistinės medžiagos kiekis prasiskverbęs į dermą, po odos pažeidimo 600 µm ilgio ir 200 µm pločio mikroadatomis, statistiškai reikšmingai nesiskyrė, skvarbai įtakos neturėjo mikroadatų ilgis., The aim of the study: to model a polymer film with lidocaine hydrochloride for coating on microneedles to achieve effective penetration of the lidoacaine hydrochloride into the skin. Research object : polymer-coated microneedles. Relevance: traditional methods of injecting lidocaine hydrochloride into the body cause pain to patients, mechanically damage to tissues and risk of microbial infection. To use of polymer-coated microneedles is considered a rational alternative to injections and means to achieve an effective delivery of drugs to the skin and such studies are considered relevant. Methods: polymer films production by solvent casting method; evaluation of physical – chemical and mechanical properties (mass, thickiness, time of dissolution, pH, humidity, stickiness, tensile force, distance to rupture point); determination penetration of the lidocaine hydrochloride into the skin by ultra high-performance liquid chromatography method. Main tasks: to form a polymer film from polyvinyl alcohol, carboxymethylcellulose sodium salt and plasticizer; to study the physical – chemical and mechanical properties of polymer films with lidocaine hydrochloride and to select the most one suitable for coating on microneedle; to evaluate the effect of different microneedles on the dermal penetration (ex vivo) of lidocaine hydrochloride from polymer solutions; to determine the dermal penetration (ex vivo) of lidocaine hydrochloride using polymer-coated microneedles. Results: formed a polymeric film from polyvinyl alcohol, carboxymethylcellulose sodium salt in a ratio 1:3 with propylene glycol in a ratio 1:20. Diffferent concentrations of 5 %, 7 % and 10 % lidocaine hydrochloride were added to the selected polymer films and the physicochemical and mechanical properties of the polymer films were investigated. Weight of the polymer films from 0,135 to 0,142 g, thickness from 154,200 to 161,800 µm, time of dissolution from 5,170 to 5,375 min humidity from 6,118 to 6,626 %, pH value from 6,397 to 6,521, top stickiness from 0,614 to 0,856 N, bottom from 0,590 to 0,956 N, tensile force from 7,259 to 8,105 N, the distance to the rupture point from 7,992 to 8,317 mm. After testing these properties a polymer film with 10 % lidocaine hydrochloride was selected according to the highest top (0,856 N) and bottom (0,956 N) stickiness, humidity (6,626 %) and tensile force (8,105 N), the distance to the rupture point (8,317 mm). The highest penetration of lidocaine hydrochloride from polymer solutions into the skin was using 800 µm lenght and 400 µm width and 600 µm lenght and 600 µm lenght and 200 µm width microneedles. The minimum penetration of lidocaine hydrochloride was using 400 µm lenght and 200 µm width microneedles. The highest dermal penetration of lidocaine hydrochloride was using 600 µm lenght and 200 µm width polymer-coated microneedles. The minimum dermal penetration of lidocaine hydrochloride was using 800 µm lenght and 400 µm width microneedles. Conclusions: the polymer film formed from polyvinyl alcohol and carboxymethylcellulose sodium salt with propylene glycol was with suitable properties for the incorporation of the model drug–lidocaine hydrochloride. After incorporating different amounts of lidocaine hydrochloride into the polymer films and investigated their physicochemical and mechanical properties, properties of the polymer films have changed. A polymer film with 10 % lidocaine hydrochloride was selected after evaluation of stickiness, humidity, tensile force, the distance to the rupture point. The highest penetration of lidocaine hydrochloride into the skin (ex vivo) from polymer solutions was using 800 µm lenght and 400 µm width and 600 µm lenght and 200 µm width microneedles. Minimum penetration of lidocaine hydrochloride from the damaged skin was using 400 lenght and 200 µm width microneedles. After evaluating the results of lidocaine hydrochloride for film coating were selected 800 µm lenght and 400 µm width and 600 µm lenght and 200 µm width microneedles. The amount of drug penetrated into the dermis after skin damage with 600 µm lenght and 200 µm lenght microneedles did not differ statistically significiantly, penetration was not affected by the lenght of the microneedles.

Darbo tikslas: Sumodeliuoti ir optimizuoti hidroksietilceliuliozės-polietileno oksido plėvelės sudėtį ir įvertinti jų fizikines, mechanines savybes ir biofarmacines charakteristikas. Baigiamojo magistro projekto tyrimų objektas: Hidroksietilceliuliozės-polietileno oksido sudėties plėvelės. Aktualumas: Periodonto ligų ir burnos gleivinės ligų (opų) sukeltam skausmui mažinti užtikrinant tikslų ir tiesioginį vietinių anestetikų (lidokaino hidrochlorido) dozavimą, naudojant kaip alternatyvą polimerines plėveles. Rezultatai: Eksperimentinio planavimo metu sugeneruotos 9 plėvelių sudėtys (hidroksietilceliuliozės-polietileno oksido bendras kiekis 0,4 g santykiu 2:1, 3:1 ir 4:1, PEG 400 kiekis santykiu 1:1, 1:2 ir 1:3) ir įvertintos fizikinės, mechaninės savybės: pH 6,80–7,04; tirpimo trukmė 22,3–29,8 min; drėgmės kiekis 7,7–15,9 %; lipnumas 0,248–0,477 N; tvirtumas 9,1–29,4 N ir elastingumas 9,2–14,7 mm. Nuo plastifikatoriaus PEG 400 kiekio priklausė plėvelių masė, storis, drėgmės kiekis, lipnumas, tvirtumas ir elastingumas. Į atrinktos optimalios plėvelės sudėtį (hidroksietilceliuliozės-polietileno oksido bendras kiekis 0,4 g santykiu 4:1, PEG 400 kiekis 1,2 g) buvo įterptas lidokaino hidrochloridas. Jo įterpimas statistiškai reikšmingai (p, The aim of the major thesis: To model and optimize the composition of hydroxyethylcellulosepolyethylene oxide film and to evaluate their physical, mechanical and biopharmaceutical properties. The object of research of the final master's project: Hydroxyethylcellulose-polyethylene oxide films. Relevance of the master thesis: To reduce the pain caused by periodontal diseases and oral mucosal diseases (ulcers) by providing accurate and direct dosing of local anesthetics (lidocaine hydrochloride) using polymer films as an alternative. Results: During the experimental planning, 9 film compositions were generated (total hydroxyethylcellulose-polyethylene oxide content 0,4 g in the ratio 2:1, 3:1 and 4:1, PEG 400 content in the ratio 1:1, 1:2 and 1:3) and physical and mechanical properties were evaluated: pH 6,80–7,04; dissolution time 22,3–29,8 min; moisture content 7,7–15,9 %; stickiness 0,248–0,477 N; strength 9,1–29,4 N and elasticity 9,2–14,7 mm. The weight, thickness, moisture content, tack, strength and elasticity of the films depended on the amount of plasticizer PEG 400. Lidocaine hydrochloride was incorporated into the composition of the selected optimal film (hydroxyethylcellulose-polyethylene oxide total content 0,4 g 4:1, PEG 400 content 1,2 g). Its incorporation reduced the moisture content (from 8,7 to 7,7 %), stickiness (from 0,477 to 0,273 N), strength (from 9,1 to 6,0 N), but prolonged it significantly (p

Background. Purulent wound healing is a pressing surgical challenge relevant in 30−35% of patient cases. To the more, wound infectious agents elaborate resistance to available drugs warranting the development of new drug combinations exserting a multidirectional effect on the wound process.Objective. Using a purulent wound model to experimentally evaluate the efficiency of a new multicomponent wound coating comprised of polyethylene oxide and carboxymethylcellulose sodium-immobilised dioxidine, methyluracil, metronidazole and lidocaine hydrochloride in comparison with a legal approved wound coating drug preparation of beeswax and propolis-based dioxidine ointment.Methods. The antimicrobial activity range (disk-diffusion method) and local anaesthetic effect (Rainier’s method) of the developed wound coating have been assessed. The healing process was studied in a purulent wound model with 72 Wistar rats divided between two equal groups. The following methods were applied: visual wound inspection (wound cleansing time, absence of wound-surrounding tissue oedema, granulation and epithelisation), planimetric parameter estimation (wound area, healing rate, wound area reduction ratio), wound contamination and pH measurement, wound section cell morphometry (granulocyte, macrophage, lymphocyte and fibroblast counts, cell index estimation). Daily dressings were applied for 15 days.Results. The developed wound coating exhibited high efficiency against Gram-positive and Gram-negative bacteria in the zone of inhibition tests. Its local anaesthetic effect was significantly superior to the approved drug by the duration of action. The wound area reduction was 94.2 (93.7; 94.8)% in the experimental group and 86 (84.2; 88.8)% in the control (differences statistically significant) already on day 10. A maximal healing rate in both groups was registered in phase 1 of the wound process being 1.4 times higher in experiment compared to the control. The wound contamination was significantly lower in experiment vs. control on day 8 (p = 0.0075). Wound pH negatively correlated with the fibroblast count and positively — with the contamination level.Conclusion. The study demonstrates high efficiency of the developed wound coating against infectious agents and its positive healing impact via reducing phase 1 and stimulating proliferation in phase 2 of the wound process.

This study aims to investigate the effect of compound topical anesthetic (CTA) application combined with photobiomodulation therapy (PBMT) on the level of pain perceived during placement of miniscrews and 24 h post the procedure in the buccal side of the maxillary bone. This randomized, prospective, single-center, split-mouth, double-blinded study included 25 subjects (12 males and 13 females, aged 16 to 35). Two anesthetic techniques before implantation were performed including Profound gel +PBM with 980 nm diode laser and local anesthesia with 2% lidocaine hydrochloride. Then, the miniscrews with the size of 1.6 mm in diameter and 8 mm in length were placed with a hand driver in the buccal side of the maxillary bone. The pain immediately after miniscrew placement (T1), also 12 h (T2), and 24 h (T3) post the procedure were collected by visual analog scale (VAS). Data were analyzed by SPSS version 22. There were no statistically significant differences in mean VAS scores within or between CTA combined with PBMT or injection applications, immediately after miniscrew placement (P = 0.75), 12 h after miniscrew placement (P = 0.4), and 24 h after miniscrew placement (P = 1.0). Compound topical anesthetic combined with PBMT provided adequate local anesthesia for the placement of miniscrews in the buccal side of the maxillary bone.

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 properties of sodium hyaluronate (HA), such as hygroscopicity, flexibility, the ability to form hydrogels, as well as biocompatibility and biodegradability, are beneficial for the applications in pharmaceutical technology, cosmetics industry, and aesthetic medicine. The aim of this study was to prepare HA-based hydrogels doped with active pharmaceutical ingredient (API): a cationic drug—lidocaine hydrochloride or anionic drug—sodium. The interaction between the carrier and the implemented active pharmaceutical substances was evaluated in prepared systems by applying viscometric measurements, performing release tests of the drug from the obtained formulations, and carrying out FTIR and DSC. The data from release studies were analyzed using the zero-, first-, and second-order kinetics and Higuchi, Korsmeyer-Peppas, and Hixon-Crowell models. The respective kinetic parameters: the release rate constants, the half-release time and, in the case of the Korsmeyer-Peppas equation, the n parameter were calculated. The variability between the obtained release profiles was studied by calculating the difference (f1) and the similarity factor (f2) as well as employing statistical methods. It was revealed that the incorporation of the drugs resulted in an increase in the viscosity of the hydrogels in comparison to the respective drug-free preparations. The dissolution study showed that not entire amount of the added drug was released from the formulation, suggesting an interaction between the carrier and the drug. The FTIR and DSC studies confirmed the bond formation between HA and both medicinal substances.

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

Background: The pain caused by the injection of local anesthetic has been reported as one of the main complaints of dental patients. Topical anesthetics are widely used drugs in dentistry, mainly to control pain associated with the needle penetration in the administration of local anesthesia. Objective: The present study aimed to evaluate (5%,7.5% and 10%) concentrations of lidocaine/prilocaine agent, compared to the common 10% lidocaine hydrochloride spray in the oral cavity. Materials and Methods: This was a split-mouth double-blind, randomized clinical trial pilot study. We randomized 15 patients, ages 35 to 64 years, with American Society of Anesthesiologists I and II with severe chronic periodontitis who were referred to the dental clinic for surgery, to receive 4 topical anesthetics (5%, 7.5%, and 10%) lidocaine prilocaine emulsion and 10% lidocaine hydrochloride topical anesthetic agent before local infiltration. Primary outcomes were assessing drug safety and pain level that measured by assessment of visual analog scale (VAS) scores of pain during LA injection in the first premolar and second molar in each maxillary quadrant in 15 patients corresponding to the posterior superior alveolar nerve (PSA) and secondary outcome was the relationship between age and gender regarding pain perception, and a total of 60 regions were analyzed. Results: Results revealed that there was no statistically significant difference between lidocaine hydrochloride and (5%,7.5% and 10%) lidocaine prilocaine in terms of pain reduction when the 4 different compounds were compared. According to Spearman's rank correlation coefficient and Friedman test, the age and gender of the patients had an insignificant correlation with the anesthetic effects of the four studied solutions. Conclusion: Based on these results, age and gender have insignificant effects on the pain scores and it can be said that the four solutions do not have significant differences regarding their anesthetic effects; also, we did not find any adverse reactions by using 7.5% and 10% lidocaine/prilocaine agent.

Acute otitis media is a common disease in children and accounts for about 2% of the total child morbidity. In the largest percentage of cases, acute otitis is usually successfully resolved, but its relapses increase the possibility of complications and lead to higher treatment costs, as well as lower quality of life for both the patient and his or her family in general. Therapy of acute otitis media depends on the stage of disease development and clinical manifestations and is aimed at early resolution of inflammatory process and prevention of disease progress and complications development. Pathogenetic therapy is shown at the 1 st and 2 nd stages of development of acute otitis media and is based on restoration of auditory tube function and normalization of nasal breathing (unloading – intranasal therapy). As a local analgesic therapy for acute otitis media in children, ear drops containing non-opioid analgesic antipyretic drug phenazone and lidocaine, consisting of a combination of phenazone (40 mg) and lidocaine hydrochloride (10 mg), are most commonly used. Phenazone is a nonsteroidal anti-inflammatory drug and has an anti-inflammatory effect, typical for non-selective inhibitors of cyclooxygenase, while lidocaine has a local analgesic effect. Based on the clinical trials conducted, it was recommended to include combined topical drugs as a local analgesic and anti-inflammatory drug with effective action and good tolerability in all age groups into the combined therapy of acute preperforative otitis media.

Introduction: Among various carrier materials capable of drug controlled-release, silica xerogels have been found to be noteworthy for loading and sustaining drug release. These silica xerogels were synthesized through sol-gel technology using Tetraethylortosilicate (TEOS) as a silica precursor. Methods: This study was an experimental basic research, which aimed to characterize the effect of adding chitosan to silica xerogels on Morphology, surface area and topography as well as mechanical behavior of the hybrid films. Furthermore, the lidocaine hydrochloride was incorporated on to the hybrid chitosan-silica xerogels and drug release behavior of the hybrid xerogels was evaluated and compared with pure silica xerogels. In addition, the covalent bond between chitosan chains and silica network was verified by FTIR; MTT assay was performed to evaluate cytotoxicity of the final system. Results: The release profile of hybrid xerogels showed biphasic mode of release and approximately 71 % accumulative release rate. Chitosan slightly decreased burst effect and release rate, but extended release period in comparison with silica xerogel. Moreover, blending of chitosan and TEOS enhanced tensile elongation and reduced the average pore size of TEOS-based xerogels. Conclusion: In conclusion, this in vitro study showed that the sol–gel method is useful for entrapping lidocaine hydrochloride in the pores of xerogels and its controlled release. Likewise, blending of chitosan and TEOS improves tensile mechanical properties of resulted biocompatible films. Hence, the final organic-inorganic films are capable to be applied as a coating or thin films in biomedical applications.

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.

ObjectiveThis study investigated the risk of contamination of lidocaine hydrochloride 5 per cent w/v and phenylephrine hydrochloride 0.5 per cent w/v topical solution after modification of the application technique.MethodsThis paper reports a prospective basic sciences study involving 22 study samples and 1 control sample of the lidocaine hydrochloride and phenylephrine hydrochloride topical anaesthetic spray. The samples were assessed for microbiological contamination after a single use on patients using a modified application technique. The modification involves keeping the nozzle (actuator) pressed down whilst withdrawing the spray to at least 30 cm (1 ft) from the patient, before releasing the nozzle (actuator) and subsequently reapplying the spray.ResultsThree of the 23 samples confirmed bacterial growth in the bottle contents, but there was no growth in any of the samples from the pump. These bacteria are considered to be contaminants.ConclusionThere is a potential to use the lidocaine hydrochloride 5 per cent w/v and phenylephrine hydrochloride 0.5 per cent w/v topical solution as a multi-use spray by changing the actuator between patients. This would have significant beneficial cost implications without the attendant infection control risk.

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.

Background Disturbances in pancreatic microcirculation, beginning with vasoconstriction, are crucial in early pancreatitis and progression to necrotizing pancreatitis. Thus, vascular-targeted treatment aiming to restore a sufficient level of microcirculation through vasodilation would possibly reduce the severity of pancreatitis. Lidocaine is an anti-arrhythmic and local anesthetic drug, which also acts as a vasodilator at higher concentrations. Objectives To evaluate the efficacy of intra-arterial infusion of lidocaine into the celiac trunk in treatment of cerulein-induced acute pancreatitis. Material and methods Wistar rats (n = 20) were randomly divided into 2 equal groups: the control group (NaCl group, n = 10) and the study group (lidocaine group, n = 10). All subjects underwent surgical intervention with intra-arterial infusion of 0.9% NaCl (control group) or 1% lidocaine hydrochloride (study group) into the celiac trunk. Blood samples were collected 5 times at regular intervals from each rat for amylase and lipase measurements. Histopathological analysis of the pancreas was performed. Results A total number of 16 rats (control group n = 7, study group n = 9) were included. In the postoperative course, the study group (lidocaine group) revealed lower values of serum amylase and lipase levels compared to the control group (NaCl group), except the values at the 1st treatment point, which appeared 1 h after intraoperative drug injection. Significantly lower treatment endpoint levels of pancreatic enzymes were seen in the lidocaine group. Moreover, no differences were observed between the 1st and the last treatment point in the control group; however, these differences were significant for both enzymes in the study group. Histopathology revealed reduced pancreatitis severity in the study group compared to the controls. Conclusions Intra-arterial lidocaine infusion into the celiac trunk decreases pancreatitis severity. What is more, this study demonstrates the relevance of early vasodilation in the therapy of acute pancreatitis.

Background: Lidocaine hydrochloride is frequently used for management of painful wounds. This prospective, multicentre study examined the effects of 5% lidocaine cream on wound pain relief. Material and methods: The study included 78 patients with painful wounds treated with 5% Lidocaine cream for two weeks in two Italian Hospitals. Patients’ perception of pain was recorded by, using the 5-point Visual Rate Scale and the 11-point Numerical Pain Rating Scale. All medications and adverse events were evaluated in a daily diary. The primary outcome of the study was establishing the wound pain relief based on the results of 5-VRS and pain intensity based on the 11-NPRS testing from baseline to the end of treatment. Clinical aspects and adverse events were also collected. Results: Seventy-eight patients had a median age of 67.5 years (range 18-96 years). 62.8% were women. The wounds included traumatic wounds (n = 39), venous ulcers (n = 25), post-surgical wounds (n = 6) pyoderma gangrenosum (n = 6), vasculitis (n = 1) and pressure ulcer (n = 1). The intensity of pain significantly decreased from the baseline level established at the beginning of treatment (mean score 6.7 − 1.90) - to the level at end of treatment (3.0 − 2.23-; p < 0.0001). 9 patients prematurely stopped the treatment for healing (n = 4), wound improvement (n = 2) and adverse events related to the treatment. (n = 3). 13 patients presented a total of 25 adverse events, 4 of them were related to the treatment. Conclusion: The treatment of painful wounds with 5% Lidocaine Cream for 14 days resulted in reduced pain intensity, and showed high safety and tolerability.

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

Background/Aims: Morphine causes state-dependent learning that its mechanism and brain-related structures are not fully understood. This study aimed to determine whether lidocaine reversible inactivation of the central nucleus of the amygdala (CeA) could affect acquisition, consolidation, and retrieval of morphine state-dependent learning. Methods: One hundred twenty male Wistar rats were allocated into 15 experimental groups. Subcutaneous administration of morphine (5 mg/kg) induced morphine state-dependent learning. Intra-CeA injection of Lidocaine hydrochloride was performed 5 min before each morphine session for transient inactivation of the CeA. The step-through latency and the time spent in the dark compartment were measured using passive avoidance learning task. Results: Our results showed that pretraining, posttraining, and pretest inhibition of the CeA severely impaired acquisition, consolidation, and retrieval of morphine state-dependent learning. Conclusion: These data revealed the involvement of the CeA in different stages of memory and morphine state-dependent learning.

Purpose Nasolabial folds (NLFs) are one of the most noticeable signs of facial aging. NLFs negatively affect self-confidence and social acceptance often leading to a person’s desire to improve their appearance using dermal fillers. The hyaluronic acid injectable gel implant Princess® FILLER Lidocaine (PFL) is a minimally invasive easy to administer the product. In this investigation, we assessed the safety and efficacy of PFL to correct moderate to severe NLFs over a 36-week period. Methods Adult women and men with moderate to severe NLFs received one injection of PFL to both NLFs. After 2 weeks, a touch-up treatment could be performed, if deemed necessary by the investigator. The change in NLF severity was assessed using the Nasolabial Fold Severity Rating Scale (NFL-SRS) developed by Croma-Pharma and the Global Aesthetic Improvement Scale (GAIS). Results Out of 60 analyzed subjects, 59 (98.3%) had improved their NLF severity by at least 1 grade on the NFL-SRS at week 4, 58 subjects (96.7%) at weeks 24 and 36. All subjects showed aesthetic improvement (GAIS), at weeks 4 and 24. The investigator judged the aesthetics as very much improved (score of 1) in 45 (75.0%) at week 4, 48 (80.0%) at week 24, and in 39 of 60 subjects, respectively (65.0%) at week 36. Thirty-six weeks post-initial treatment, 56 of 60 subjects (93.3%) were very satisfied or satisfied with the treatment. Adverse device effects (ADEs) were mild or moderate and resolved at latest 25 days post-onset. The most commonly reported ADEs were injection site hematoma and injection site pain. Conclusion PFL was safe and effective in reducing the severity of NLFs. Most subjects were (very) satisfied with the treatment outcome throughout a 36 weeks investigation period.

Doris Grablowitz,1 Monika Sulovsky,2 Sonja Höller,3 Zrinka Ivezic-Schoenfeld,3 Souyet Chang-Rodriguez,3 Martin Prinz3 1Medizinisch Ästhetisches Zentrum Wien, Wien 1010, Austria; 2YUVELL® Fine Aesthetics, Wien 1010, Austria; 3Croma-Pharma GmbH, Leobendorf 2100, AustriaCorrespondence: Martin PrinzCroma-Pharma GmbH, Industriezeile 6, Leobendorf 2100, AustriaTel +43 2262 684 68-0Fax +43 2262 684 68-165Email martin.prinz@croma.atPurpose: Nasolabial folds (NLFs) are one of the most noticeable signs of facial aging. NLFs negatively affect self-confidence and social acceptance often leading to a person’s desire to improve their appearance using dermal fillers. The hyaluronic acid injectable gel implant Princess® FILLER Lidocaine (PFL) is a minimally invasive easy to administer the product. In this investigation, we assessed the safety and efficacy of PFL to correct moderate to severe NLFs over a 36-week period.Methods: Adult women and men with moderate to severe NLFs received one injection of PFL to both NLFs. After 2 weeks, a touch-up treatment could be performed, if deemed necessary by the investigator. The change in NLF severity was assessed using the Nasolabial Fold Severity Rating Scale (NFL-SRS) developed by Croma-Pharma and the Global Aesthetic Improvement Scale (GAIS).Results: Out of 60 analyzed subjects, 59 (98.3%) had improved their NLF severity by at least 1 grade on the NFL-SRS at week 4, 58 subjects (96.7%) at weeks 24 and 36. All subjects showed aesthetic improvement (GAIS), at weeks 4 and 24. The investigator judged the aesthetics as very much improved (score of 1) in 45 (75.0%) at week 4, 48 (80.0%) at week 24, and in 39 of 60 subjects, respectively (65.0%) at week 36. Thirty-six weeks post-initial treatment, 56 of 60 subjects (93.3%) were very satisfied or satisfied with the treatment. Adverse device effects (ADEs) were mild or moderate and resolved at latest 25 days post-onset. The most commonly reported ADEs were injection site hematoma and injection site pain.Conclusion: PFL was safe and effective in reducing the severity of NLFs. Most subjects were (very) satisfied with the treatment outcome throughout a 36 weeks investigation period.Keywords: hyaluronic acid, dermal filler, lidocaine hydrochloride, mid to deep dermis, facial wrinkles, injection

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)...

Li-Zhou Wang,1,&ast; Xiao-Xia Hu,2,&ast; Xiang-Chun Shen,2,3 Tian-Cheng Wang,4 Shi Zhou1 1Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2The State Laboratory of Functions and Application of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 4Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Cheng WangDepartment of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86 15073190153Email 421176806@qq.comShi ZhouDepartment of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of ChinaTel +86 13809477708Email zhoushi@gmc.edu.cnObjective: To investigate the sustained release of lidocaine from a lidocaine–epirubicin–lipiodol emulsion created by water-in-oil (W/O) technique in vivo and evaluate the efficacy and safety of intraarterial lidocaine administration for intra- and postoperative pain control in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods: The in vivo concentrations of lidocaine were determined in tumor tissues after VX2 rabbit models for hepatic tumor were administered with intra-arterial lidocaine–epirubicin–lipiodol emulsion. A prospective randomized controlled clinical trial was performed, enrolling 70 consecutive patients who underwent TACE. Patients were randomized into two groups: Group A received an immediate bolus intraarterial lidocaine injection before TACE, and Group B received a lidocaine–epirubicin–lipiodol emulsion during TACE. Pain intensity was compared between the two groups using a visual analog scale (VAS) score before (Tbefore) and at 0 h (T0), 4 h (T4), 8 h (T8), 24 h (T24), 48 h (T48), and 72 h (T72) after the procedure. Adverse events and intake of analgesics were evaluated and compared between the two groups.Results: The concentrations of lidocaine in tumor tissues were higher in experimental group than in control group at T0.5 (P=0.004), T1 (P=0.038), T4 (P=0.036), and T8 (P=0.029). In the clinical trial, VAS scores in Group B were significantly lower than in Group A at T0 (P=0.006), T4 (P=0.001), T8 (P=0.002), and T24 (P=0.005). The tramadol intake in Group B was significantly lower than in Group A (P=0.021). No significant difference was observed regarding the incidence of adverse events between the two groups.Conclusion: This study demonstrated the effectiveness and safety of intraarterial lidocaine administration using the W/O technique in controlling intra- and post-TACE pain.Keywords: carcinoma, hepatocellular, chemoembolization, therapeutic, lidocaine hydrochloride, pain management

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.

BackgroundWe investigated the role of epinephrine in prolonging the localization of lidocaine on the oral mucosa and inhibiting its absorption in the blood of rats.MethodsWe used 7–8-week-old pathogen-free Wistar male rats (n = 128) for our study. We divided them into the control group administered with14C-labeled lidocaine hydrochloride gel only and the study group administered with14C-labeled lidocaine hydrochloride gel with epinephrine. The medications were administered in the palatal mucosa of the rats. The amount of mucosa, palatine bone, and serum lidocaine was measured by radioactivity using a liquid scintillation counter and was observed using autoradiograms.ResultsInitially, there was no significant difference in the lidocaine levels between the lidocaine and lidocaine with epinephrine groups in the palatal mucosa (751.9 ± 133.8 vs. 669.8 ± 101.6 ng/mg [2 min]). After 4 min, the values were significantly lower in the lidocaine with epinephrine group (1040.0 ± 142.8 vs. 701.2 ± 109.0 ng/mg [20 min]). After 40 min, the lidocaine level became significantly higher in the lidocaine with epinephrine group (586.8 ± 112.4 vs. 1131.3 ± 155.2 ng/mg [40 min]). Similar results were observed in the palatine bone and serum.ConclusionEpinephrine prolonged the localization of lidocaine applied to the mucosa and inhibited its absorption into the bloodstream of rats. Clinical studies are required to evaluate the use of epinephrine-containing topical anesthetics on the oral mucosa.

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.

Darbo tikslas: sumodeliuoti ir optimizuoti kokybės reikalavimus atitinkančias polivinilo alkoholio ir karboksimetilceliuliozės natrio druskos mišinio plėveles su lidokaino hidrochloridu ir atlikti biofarmacinį vertinimą. Darbo uždaviniai: sumodeliuoti ir optimizuoti polivinilo alkoholio ir karboksimetilceliuliozės natrio druskos mišinio plėvelių sudėtis pagal pasirinktus kokybės parametrus; įvertinti atrinktų plėvelių fizikines-chemines ir mechanines savybes; įvertinti polivinilo alkoholio ir karboksimetilceliuliozės natrio druskos mišinio plėvelių su lidokaino hidrochlorido fizikines-chemines ir mechanines savybes; įvertinti lidokaino hidrochlorido atpalaidavimą iš polivinilo alkoholio ir karboksimetilceliuliozės natrio druskos mišinio plėvelių. Tyrimų objektas: Polivinilo alkoholio ir karboksimetilceliuliozės natrio druskos mišinio plėvelės. Aktualumas: Pacientų diskomforto ar psichologinių baimių ir dermatologinių produktų trūkumų sprendimas kuriant ir gaminant polimerines plėveles. Metodai: eksperimentinių plėvelių sudėties modeliavimas; plėvelių gamyba liejimo būdu; fizikinių-cheminių savybių įvertinimas (masės vienodumas, storio vienodumas, pH, tirpinimo testas, drėgmės nustatymas); mechaninių savybių įvertinimas (plyšimo jėgos ir lipnumo nustatymas); lidokaino hidrochlorido kiekio vienodumas plėvelėse; lidokaino hidrochlorido atpalaidavimas in vitro; ultra efektyvios skysčių chromatografijos metodas. Rezultatai: į atrinktas plėvelių sudėtis (karboksimetilceliuliozės natrio druska ir polivinilo alkoholis santykiu 3:1 ir 1,2-propandiolio kiekis buvo 2,0 g ar 2,5 g) buvo įterptas lidokaino hidrochloridas. Šių plėvelių fizikines-chemines savybes: pH vertė 6,4–6,5, drėgmė 5–6,2% ir tirpumas buvo 35–43 min. Mechaninės savybės: plyšimo jėga 6–9 N, atstumas iki plyšimo 6–9 mm ir lipnumas 0,308–0,444 N. Įterpus lidokaino hidrochloridą į atrinktos sudėties plėveles fizikinės-cheminės savybės išliko panašios, išskyrus mechanines savybes, kurios sumažėjo (plyšimo jėga, atstumas iki plyšimo ir lipnumas). Atlikus in vitro tyrimą nustatyta, kad iš polimerinių plėvelių lidokaino hidrochlorido buvo atpalaiduota 1260–1327 μg/cm2. Išvados: Pasirinkti kokybės parametrai leido sumodeliuoti ir atsirinkti plėveles. Tyrimo metu nebuvo gautas statistiškai reikšmingas matematinis modelis pagal, kurį būtų galima prognozuoti fizikines-chemines ir mechanines savybes. Įvertinus kokybės parametrus buvo gautos plėvelės tinkamos naudoti ant odos. Plėvelės yra tinkamos lidokaino hidrochloridą tiekti į organizmą, The aim of work: modeling and optimization quality-compliant polyvinyl alcohol and carboxymethylcellulose sodium salt blend films with lidocaine hydrochloride and perform biopharmaceutical assessment. Main tasks: modeling and optimization polyvinyl alcohol and carboxymethylcellulose sodium salt blend films based on the selected parameters; to evaluate the physical-chemical and mechanical properties of selected films; to evaluate the physico-chemical and mechanical properties of polyvinyl alcohol and carboxymethylcellulose sodium salt blend films; to evaluate release of lidocaine hydrochloride from of polyvinyl alcohol and carboxymethylcellulose sodium salt blend films. Research object: polyvinyl alcohol and carboxymethylcellulose sodium salt blend films. Actuality: polymeric films are a solution of patient discomfort or psychological fears and deficiencies of dermatological products. Methods: experimental films composition optimization; films production for solvent casting method; evaluation of physico-chemical properties (uniformity of mass and thickness, pH, time of dissolution, determination of humidity) and mechanical properties (determination of tensile force and stickiness); uniformity of lidocaine hydrochloride in films; in vitro release of lidocaine hydrochloride; ultra-high performance liquid chromatography method. Results: to selected composition films (carboxymethylcellulose sodium salt and polyvinyl alcohol ratio 3:1 and 1 2-propanediol quantity 2,0 g or 2,5 g) were to inserted lidocaine hydrochloride. The physico-chemical properties of these films were: pH value from 6.4 to 6.5, the moisture content ranges from 5 to 6.2 % and time of dissolution from 35 to 43 min. The mechanical properties of these films were: tensile force from 6 to 9 N, distance to rupture point from 6 to 9 mm ant stickiness from 0,308 to 0,444 N. The physico-chemical properties of selected composition films inserted lidocaine hydrochloride remained the same but mechanical properties decreased (tensile force, distance to rupture point and stickiness). In vitro studies lidocaine hydrochloride was released from polymer films from 1260 to 1327 μg/cm2. Conclutions: the selected qualitative parameters allowed to model and select the films. In these studies were not get statistic significant mathematical model which to predict physico-chemical and mechanical properties. After evaluating qualitative properties of films were suitable for use on the skin. Polymer films are suitable for lidocaine hydrochloride release.