Search

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. [ABSTRACT FROM AUTHOR]

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 pathological bacteria. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (in <5 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. [ABSTRACT FROM AUTHOR]

Fluorescent carbon dots (CDs) were synthesized through hydrothermal treatment of an easily available fish scales precursor. The as-prepared CDs exhibit good water-solubility, wavelength-tunable fluorescence nature with fluorescence quantum yield of 9%, high photostability and resistance against common ions and biomolecules, thus enables the application as viable fluorescent nanoprobes for detection of pharmaceuticals molecules. The fluorescence of CDs can be efficiently quenched by lidocaine hydrochloride (LH) through static quenching, hence the CDs can serve as a simple and rapid fluorescent probe for determination of LH pharmaceutical. The fluorescent CDs probe demonstrated a wide linear range (0.185–1.295 mmol L −1 ) and a low detection limit (0.054 mmol L −1 ). The CDs also demonstrates low cytotoxicity, which enables the accurate fluorescent detection of LH in human serum. [ABSTRACT FROM AUTHOR]

The application of aggregation behavior of a surface active ionic liquids (SAILs), 1-dodecyl-3-methylimidazolium chloride [C 12 mim][Cl] and 1-tetradecyl-3-methylimidazolium chloride [C 14 mim][Cl] in drug delivery of lidocaine hydrochloride has been investigated from surface tension and fluorescence measurements at 298.15 K and from conductance at 288.15, 298.15 and 308.15 K. Critical aggregation concentration ( CAC ), degree of ionization ( α ), and various thermodynamic parameters like Gibbs free energy of aggregation (∆ G agg . ° ) standard enthalpy of aggregation (∆ H agg . ° ) and standard entropy of aggregation (∆ S agg . ° ) are calculated using conductivity measurements. The surface activity of the ILs in various mixed solvents are examined from surface tension measurements by calculating various surface parameters like maximum surface excess concentration (Г max ), minimum surface area per ionic liquid molecule (A min ), adsorption efficiency (pC 20 ), effectiveness of surface tension reduction ( Π cac ) surface tension at CAC ( γ cac ), p (packing parameter), and CAC at different compositions. Fluorescence measurements have been employed to get detailed insight of the local microenvironment of the aggregates, and critical aggregation concentration ( CAC ). Decrease in the CAC values was observed with the increase in the amount of drug which is attributed to the balancing between electrostatic and hydrophobic interactions. This shows that the spontaneity of aggregation process of IL increases with the increase in the concentration of drug. [ABSTRACT FROM AUTHOR]

The current study investigated the effect of temporary inhibition of amygdala in response to metabolic changes caused by stress in female mice. Unilateral and bilateral amygdala cannulation was carried out, and after a week of recovery, 2% lidocaine hydrochloride was injected into the mice amygdalae five minutes before the induction of stress. A communication box was employed to induce stress for four consecutive days and plasma corticosterone, food and water intake, weight changes, and anorexia were measured as stress-induced metabolic changes. Results demonstrated that stress, increases stress, increased plasma corticosterone concentrations, weight, food, and water intake. Temporary inhibition of the amygdala slightly decreased plasma corticosterone concentrations, but did not fully reduce the effect of stress. The bilateral injection of lidocaine hydrochloride to the amygdala reduced the effect of stress and reduced water intake and weight. Unilateral injection of lidocaine hydrochloride into the left and right amygdala reduced food intake. In conclusion, the present study demonstrated that the left side and right side of amygdala nuclei play a different role in metabolic responses in stress. [ABSTRACT FROM AUTHOR]

Buccal administration of sumatriptan succinate might be an interesting alternative to the present administration routes, due to its non-invasiveness and rapid onset of action, but because of its low permeability, a permeation enhancement strategy is required. The aim of this work was then to study, in-vitro , buccal iontophoresis of sumatriptan succinate. Permeation experiments were performed in-vitro across pig esophageal epithelium, a recently proposed model of human buccal mucosa, using vertical diffusion cells. The iontophoretic behavior of the tissue was characterized by measuring its isoelectric point (Na + transport number and the electroosmotic flow of acetaminophen determination) and by evaluating tissue integrity after current application. The results obtained confirm the usefulness of pig esophageal epithelium as an in-vitro model membrane for buccal drug delivery. The application of iontophoresis increased sumatriptan transport, proportionally to the current density applied, without tissue damage: electrotransport was the predominant mechanism. Integrating the results of the present work with literature data on the transport of other molecules across the buccal mucosa and across the skin, we can draw a general conclusion: the difference in passive transport across buccal mucosa and across the skin is influenced by permeant lipophilicity and by the penetration pathway. Finally, buccal iontophoretic administration of sumatriptan allows to administer 6 mg of the drug in 1 h, representing a promising alternative to the current administration routes. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) hydrogels cross-linked with the tetrahydroxyborate anion possess textural and rheological properties that can be used as novel drug-loaded vehicles for application to traumatic wounds. However, addition of soluble drug substances causes concentration-dependent phase separation and rheological changes. The aim of this work was to investigate the effect of adding a local anaesthetic, but keeping the concentration low in an attempt to prevent these changes. Cross-linked hydrogels prepared from three grades of poly(vinyl alcohol) were characterised rheologically. Temperature sweep studies showed an elevated complex viscosity upon moving from 25 °C to 80 °C, which remained high for 48 h following completion of the cycle. Adhesion to model dermal surfaces achieved a maximum of 2.62 N cm −2 and were greater than that observed to epidermal substrates, with a strong dependence on the rate of detachment used during testing. An optimised formulation (6% w/w PVA (31–50; 99) and 2% w/w THB) containing lidocaine hydrochloride loaded to an upper maximum concentration of 1.5% w/w was assessed for phase separation and drug crystallisation. After six months, crystallisation was present in formulations containing 0.7% and 1.5% lidocaine HCl. Changes in pH in response to increases in lidocaine loading were low. Drug release was shown to operate via a non-Fickian process for all three concentrations, with 60% occurring after approximately 24 h. It can be concluded that using a low concentration of lidocaine hydrochloride in hydrogels based on poly(vinyl alcohol) will result in crystallisation. Furthermore, these hydrogels are unlikely to induce rapid anaesthesia due to the low loading and slow release kinetics. [ABSTRACT FROM AUTHOR]

Cav3.1 is a low-voltage-activated (LVA) calcium channel that plays a key role in regulating intracellular calcium ion levels. In this study, we observed the effects of lidocaine hydrochloride on the pshRNA-CACNA1G-SH-SY5Y cells that silenced Cav3.1 mRNA by RNA interference, and investigated the roles of p38 MAPK in these effects. We constructed the pNC-puro-CACNA1G-SH-SY5Y cells and pshRNA-CACNA1G –SH-SY5Y cells by the RNA interference. All the cells were cultured with or without 10 mM lidocaine hydrochloride for 24 h. The cell morphology, cell viability, Cav3.1 and p38 protein expression, cell apoptosis rate and intracellular calcium ion concentration were detected. We found that all cells treated with 10 mM lidocaine hydrochloride for 24 h showed cellular rounding, axonal regression, and cellular floating. Compared with the cells in SH-SY5Y+Lido group and NC+Lido group, those in the RNAi+Lido group showed similar changes, but of smaller magnitude. Additionally, following lidocaine hydrochloride all cells displayed increased Cav3.1 and p38 MAPK protein, apoptosis rate, and intracellular calcium ion levels; however,these changes in the RNAi+Lido group were less pronounced than in the SH-SY5Y+Lido and NC+Lido groups. The cell viability decreased following lidocaine hydrochloride treatment, but viability of the cells in the RNAi+Lido group was higher than in the SH-SY5Y+Lido and NC+Lido groups. The results showed that Cav3.1 may be involved in neuronal injury induced by lidocaine hydrochloride and that p38 MAPK phosphorylation was reduced upon Cav3.1 gene silencing. [ABSTRACT FROM AUTHOR]

Skin penetration enhancers (SPEs) are commonly employed in pharmaceutical and personal care products. These compounds transiently alter the barrier properties of the skin and we have previously investigated the effects of specific SPEs on skin barrier function in vivo . In the present study the effects of incorporation of an active pharmaceutical ingredient (API), lidocaine hydrochloride (LID HCl) in the SPEs previously studied were investigated. Solutions of LID HCl were prepared and applied to the volar forearm of human subjects with occlusion for 24 h. Subsequently, tape stripping and trans epidermal water loss (TEWL) measurements were conducted for treated and control sites. The activities of the desquamatory proteases, kallikrein 5 (KLK 5) and kallikrein 7 (KLK 7) and API content were also measured from the tape strips. The propylene glycol (PG) formulation increased TEWL significantly ( p < 0.05) compared with the other SPEs and a mixture of the SPEs. However, only the isopropyl myristate (IPM) solution altered protease activity with a significant observed increase in kallikrein 5 (KLK 5). Incorporation of LID HCl appeared to ameliorate the effects of some of the SPEs on TEWL measurements compared with our previous study. Overall uptake of LID HCl into skin from the various formulations correlated very well with changes in TEWL. The findings should have implications for the choice of SPEs in topical and transdermal formulations, particularly where the skin barrier function of patients is already impaired for example in atopic eczema or psoriasis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Successive spectrophotometric resolution for severely overlapped spectra. [•] Each component could be obtained alone as its D0 by CM only, or RS & SRS–CM. [•] Each component could be obtained alone as its D1 by CM only or by DS & SDS–CM. [•] They were applied for the analysis of their pharmaceutical formulation. [•] Validated according to the ICH guidelines & compared to the official methods. [Copyright &y& Elsevier]

Abstract: This study reveals and highlights the importance of the electrospinning set-up to avoid the occurrence of ionic interaction between drugs during the preparation of dual drug loaded electrospun fibrous materials. Poly(L-lactide) (PLA)-based fibrous materials containing diclofenac sodium (DS) and lidocaine hydrochloride (LHC) were prepared by dual spinneret electrospinning of two separate solutions each containing one drug only [(PLA/DS and PLA/LHC)] and compared with materials obtained by electrospinning of a common solution (PLA/DS/LHC) using a single spinneret. Interestingly, the dual spinneret approach allowed the ionic interaction between DS and LHC to be obviated. This was evidenced by the absence of NaCl crystals in the case of (PLA/DS+PLA/LHC) membranes as proven by scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD). The XRD and differential scanning calorimetric analyses revealed that the drugs were in the amorphous state regardless of the method of preparation of the fibrous materials. It was found that PLA/DS/LHC and (PLA/DS+PLA/LHC) fibrous materials exhibited antimicrobial activity against Staphylococcus aureus and were cytocompatible with human mesenchymal stem cells. [Copyright &y& Elsevier]

The renewable fatty acid-based surface-active ionic liquids (SAILs) containing ethyl-substituted imidazolium head groups were prepared and structurally analyzed by Fourier transform infrared spectroscopy (FTIR), 1HNMR and 13CNMR spectroscopy. The products were named as; 3-ethyl-1-(2-dodecanoyl oxy) ethylimidazolium bromide [C 12 Eeim]Br, 3-ethyl-1-(2-tetradecanoyl oxy) ethylimidazolium bromide [C 14 Eeim]Br and 3-ethyl-1-(2-hexadecanoyl oxy) ethylimidazolium bromide [C 16 Eeim]Br. The critical micelle concentration (cmc) values of the three SAILs have been evaluated using conductivity measurements, probe-less UV–visible spectroscopy and fluorescence spectroscopy. The obtained cmc values were compared with the earlier reported non-functionalized SAILs such as [C n mim]Br and [C n eim]Br where n = 12, 14, 16. The values were found to be 3–9 times lower mainly due to the presence of ester chain and also ethyl substituted imidazole ring. Thermodynamic parameters were evaluated by conductivity data at three different temperatures. Further, the aggregation behavior of SAILs with anesthetic drug, lidocaine hydrochloride (LC) has been studied using fluorescence. The fluorescence and UV–visible studies showed strong synergistic interactions operating between SAILs and drug molecules involving H bonding and cation-π interactions. The interactions grew stronger with the elongation of SAIL-chain length (12–16C). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements suggested the formation of vesicles in SAIL-LC mixtures. These studies may thus offer an effective candidate which would serve as vectors for drug molecules in terms of their enhanced solubilization, permeability and target-specific delivery. [Display omitted] • A series of fatty acid-imidazolium-based SAILs were synthesized and characterized by multiple spectroscopic techniques. • Thermodynamic parameters showed that the process of micellization is exothermic and entropy-driven. • The spectroscopic studies confirmed the strong synergistic interactions between SAIL-LC mixtures. • The microscopic studies suggested the vesicle formation in binary mixtures of SAIL and drug molecules. [ABSTRACT FROM AUTHOR]

Abstract: Transactivation transcriptional activator (TAT) peptides were conjugated on the octadecyl-quaternized, lysine-modified chitosan to form polymeric liposomes (TAT-PLs) with cholesterol for improving transdermal delivery of local anesthetic lidocaine hydrochloride (LID). In this study, the LID loaded TAT-conjugated polymeric liposomes (LID-TAT-PLs) have been successfully prepared. LID-TAT-PLs were characterized by determination of their particle size, polydispersity, morphology, drug encapsulation efficiency, drug release behavior in vitro, and storage-stability. The skin permeation of LID-TAT-PLs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and penetration of TAT-PLs was visualized by confocal laser scanning microscopy (CLSM). The results showed that LID-TAT-PLs were spherical in solution, with substantially smaller mean diameter (154.7±10.7nm), higher encapsulation efficiency (80.05±2.64%) and better stability in contrast to conventional liposomes (CLs). From the in vitro skin permeation results, transdermal flux of LID-TAT-PLs was approximately 4.17 and 1.75 times higher than that of LID solution and LID CLs (P <0.05). CLSM studies also confirmed that TAT-PLs reached viable layers of the skin. Hence, the results indicate that LID-TAT-PLs are effective and potential alternative for the LID transdermal formulation. [Copyright &y& Elsevier]

Abstract: We investigated the enhancement effect of chemical enhancers and iontophoresis on the in vitro transdermal and transbuccal delivery of lidocaine HCl (LHCl), nicotine hydrogen tartrate (NHT), and diltiazem HCl (DHCl) using porcine skin and buccal tissues. Dodecyl 2-(N,N-dimethylamino) propionate (DDAIP), dodecyl-2-(N,N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane), and azone (laurocapram) were used as chemical enhancers. The study results showed that the application of iontophoresis at either 0.1mA or 0.3mA significantly enhanced transdermal and transmucosal delivery of LHCl, NHT and DHCl. It was also demonstrated that iontophoresis had a more pronounced enhancement effect on transdermal delivery than on transbuccal delivery of LHCl, NHT and DHCl. In addition, DDAIP HCl was found to be the most effective enhancer for transbuccal delivery of LHCl and NHT. [Copyright &y& Elsevier]

Abstract: A liquid chromatographic (LC) method was developed to analyze a formulation (mouthwash) containing lidocaine hydrochloride, hydrocortisone and nystatin. A single LC method with UV detection was developed. A Waters Symmetry C18 HPLC column (150mm× 4.6mm, 5μm) was used as stationary phase and the assay was performed with gradient elution using mobile phases containing methanol – 0.1M NaH2PO4 with a pH that was previously adjusted to 4.5 with dilute phosphoric acid. The sample pretreatment was performed by treating the formulation with methanol followed by filtration. After method development, the influence of the different chromatographic parameters on the separation, the interference of other active compounds and excipients, linearity, accuracy, repeatability and intermediate precision were investigated. The method was shown to be selective, linear, accurate, precise and repeatable. Finally, the content of the compounds in the formulation was determined. [Copyright &y& Elsevier]

Abstract: Transdermal delivery is an attractive but challenging solution for delivery of drugs. The sea anemone possesses a sophisticated injection system, which utilizes built-in high osmotic pressures. The system is folded within microcapsules and upon activation it injects a long, needle-like tubule of submicron diameter that penetrates the target in a fraction of a second. Here we show that this natural injection system can be adapted for active topical drug delivery once it is isolated from the cells, formulated into a topical gel, and uploaded with the desired drug. The formulated injectors retained their physical characteristics and were capable of penetrating the skin, achieving immediate delivery of a hydrophilic compound. We demonstrate quantitative rapid delivery of lidocaine hydrochloride as a function of microcapsular and drug concentrations. The adaptation of natural injectors for drug delivery combines the benefits of short topical application with rapid delivery of physical devices, thereby presenting a promising alternative for transdermal drug delivery. [Copyright &y& Elsevier]

Abstract: The present study focused on the intercalation of lidocaine hydrochloride (LC), an antiarrhythmic local anesthetic drug into montmorillonite (MMT) as a controlled release drug carrier. The intercalation compound (MMT-LC) was characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, particle size, electrokinetic mobility and thermal analysis. MMT-LC was compounded with alginate (AL) to form a hydrogel composite and to study its release response in gastric environments. The in vitro release experiments revealed that LC was released from MMT/AL in a controlled way which was pH dependent. [Copyright &y& Elsevier]

Abstract: Lidocaine hydrochloride (LC-HCl) is widely used as a local anesthetic, while various adverse effects of LC-HCl, such as seizures have also been reported. Lidocaine is reported to inhibit various channels and receptors including GABAA receptors. Although the GABAA receptor-mediated response depends on Cl− equilibrium potential (E Cl), little is known about the effect of LC-HCl on E Cl. In the present study, we investigated the effect of LC-HCl on GABA-induced currents in cultured rat hippocampal neurons with gramicidin-perforated patch–clamp recording which is known to keep the intracellular Cl− concentration intact. LC-HCl inhibited outward GABA-induced currents with depolarizing shift of the GABA reversal potential (E GABA). The LC-HCl-induced positive E GABA shift was not observed with conventional whole-cell patch–clamp method which cannot retain intact intracellular Cl− concentration. The LC-HCl action on E GABA was inhibited by either furosemide, a blocker of both Na+-K+-Cl− cotransporter (NKCC) and K+-Cl− cotransporter (KCC), or an increase in extracellular K+ concentrations. Neither bumetanide, a specific inhibitor of NKCC, nor Na+-free external solution had any effect on the LC-HCl-induced E GABA shift. QX-314, a membrane impermeable lidocaine derivative, failed to shift E GABA to positive potential. Furthermore, LC-HCl caused a depolarizing shift of E GABA in cultured GT1-7 cells expressing KCC2 but failed to change E GABA in GT1-7 cells without expression of KCC2. These results suggest that the LC-HCl-induced positive E GABA shift is due to a blockade of KCC2. Together with the direct LC-HCl action to GABAA receptors, the positive E GABA shift induced by LC-HCl reduces the GABAergic inhibition in the central nervous system. [Copyright &y& Elsevier]

Abstract: Polyol sugars, displaying a plurality of hydroxyl groups, were shown to modulate tetrahydroxyborate (borate) cross-linking in lidocaine hydrochloride containing poly(vinyl alcohol) semi-solid hydrogels. Without polyol, demixing of borate cross-linked PVA hydrogels into two distinct phases was noticeable upon lidocaine hydrochloride addition, preventing further use as a topical system. d-Mannitol incorporation was found to be particularly suitable in circumventing network constriction induced by ionic and pH effects upon adding the hydrochloride salt of lidocaine. A test formulation (4% w/v lidocaine HCl, 2% w/v d-mannitol, 10% w/v PVA and 2.5% w/v THB) was shown to constitute an effective delivery system, which was characterised by an initial burst release and a drug release mechanism dependent on temperature, changing from a diffusion-controlled system to one with the properties of a reservoir system. The novel flow properties and innocuous adhesion of PVA–tetrahydroxyborate hydrogels support their application for drug delivery to exposed epithelial surfaces, such as lacerated wounds. Furthermore, addition of a polyol, such as d-mannitol, allows incorporation of soluble salt forms of active therapeutic agents by modulation of cross-linking density. [Copyright &y& Elsevier]

Abstract: In this paper, there was developed a sensitive, precise and accurate reversed-phase liquid chromatographic (RP-HPLC) method and validated for simultaneous determination of lidocaine hydrochloride, dexamethasone acetate (DA) and calcium dobesilate (CD) in suppositories and ointment. Also there was achieved a parallel analysis of buthylhydroxyanisol, as a preservative, and hydroquinone, as a degradation product of calcium dobesilate, present in these dosage forms. The relative standard deviation (RSD) values for all five compounds indicated a good precision and accuracy of the RP-HPLC method. Method is selective, sensitive and reproducible with good recovery values and can be applied in simultaneous determination of all mentioned compounds. [Copyright &y& Elsevier]

Abstract: The purpose of the present study was to evaluate the effect of sucrose esters (particularly, sucrose laureate and sucrose oleate in Transcutol®) on the percutaneous penetration of a charged molecule as a function of ionization. We have investigated the influence of these sucrose esters on the in vitro diffusion profiles of lidocaine hydrochloride, a weak ionizable base (pK a =7.9), at different pH values, using porcine ear skin as the barrier membrane. As expected, lidocaine flux in the absence of an enhancer, increased from pH 5 to 9 with a corrresponding increase in the level of the unionized base. However, when skin was pretreated with 2% laureate in Transcutol (2% L-TC), drug permeation was higher at pH 5.0 and 7.0 than at 9.0. A different trend was observed in experiments with 2% oleate in Transcutol (2% O-TC), where skin flux was maximal at a more basic pH, when the degree of ionization is low. The results suggest that sucrose laureate enhances the penetration of the ionized form of the drug (12-fold greater flux relative to control), whereas sucrose oleate is more effective in promoting permeation of the unionized species. The structural properties of the sucrose esters as well as the degree of ionization of the drug are important characteristics affecting the transdermal flux of lidocaine. [Copyright &y& Elsevier]

Abstract: We investigate the controlled release of lidocaine hydrochloride from the doped silica-based xerogels. In the xerogel preparation, tetraethoxysilane (TEOS), methyltriethoxysilane (MTES), and propyltriethoxysilane (PTES) are used as precursors, and a nonionic surfactant Igepal CO 720 is used as a dopant. The experimental results suggest that the release of lidocaine hydrochloride can be easily controlled by partially substituting TEOS with the organosilanes, and/or by adding the dopant. Adding the organosilane precursors lowers the release of both the drug and the surfactant in the order of TEOS, MTES/TEOS, and PTES/TEOS xerogels. The release from the PTES/TEOS xerogels is much lower than that from the other xerogels. The release of lidocaine hydrochloride is obviously suppressed by the addition of Igepal CO 720, while the release of Igepal CO 720 is slightly promoted by the addition of the drug. The overall release process is found to be diffusion-controlled, and the release behaviors can be well explained by considering the effects of the textual properties of the xerogels and the interactions among the drug, the surfactant, and the xerogel matrices. [Copyright &y& Elsevier]

Thermal gelation of Poloxamer 407 lidocaine hydrochloride gels was characterized by rheological studies. Lidocaine, a local anesthetic used for treatment of acute and chronic pain, presents short duration action; thus a long-action single-dose injection would be of clinical importance. Poloxamer 407 gel can extend the release and the action of lidocaine. In the present work, aqueous gels with lidocaine containing different concentrations of Poloxamer 407 and additives like inorganic salts (NaCl, NaH2PO4, Na2CO3) and PEG 400 were obtained. Viscosity measurements and the optimal sol–gel transition temperature were obtained by these rheological studies. Poloxamer 407 gels are viscoelastic materials because they have elastic modulus (G′), characteristic of solid materials, and viscous modulus (G″), characteristic of liquid materials. Poloxamer 407 gels are pseudoplastic; therefore, when shear deformed, their viscosity decreases. Increase of the polymer concentration increases the viscosity of the gels, which can change the releasing process of lidocaine from the gel. The sol–gel transition temperature was decreased by increasing the polymer concentration and by the presence of additives. The rheological behaviour of Poloxamer gels characterized in this work can be useful for understanding further studies of drug release. [Copyright &y& Elsevier]

Novel wound dressings were prepared using electrospun nanofibrous PLLA mats loaded with aluminum chloride (AlCl 3), gentamicin sulphate (GS) and/or lidocaine hydrochloride (LHc) as a hemostatic, antibiotic, and local anesthetic drug, respectively. Structural characterization of the prepared mats was performed using FTIR spectroscopy, whereas morphological characteristics were determined using SEM micrographs of the fibers. For mats loaded with AlCl 3 , the majority of the fibers diameters were in the range [400–500 nm]. The wettability of the mats was investigated using contact angles method. Hemostasis tests have shown that all the prepared mats have better hemostatic efficiency than gauze bandage. However, mats loaded with only AlCl 3 30%w/w have the best hemostatic performance with a decrease in blood clotting time of 80% and an increase in blood absorption capacity of 178% in comparison with gauze bandage. GS release kinetics in PBS solution was investigated. The experimental results showed that the release kinetics follows Korsmeyer-Peppas model with a correlation factor R2 = 0.999 and n = 0.1. [Display omitted] • PLLA/Drugs mats via electrospinning technique were successfully prepared. • Electrospun PLLA/aluminum chloride for hemostatic application was first introduced. • In vitro release kinetics study of gentamicin sulphate loaded on PLLA fibers. [ABSTRACT FROM AUTHOR]

• The VTMM is an effective way to quantitatively evaluate the influence of drugs and other factors on neural networks. • LC−HCl had excitatory and inhibitory biphasic effect on the electrical excitability of neural networks, while Mor−HCl had inhibitory effect. • The combined analysis showed that the V Th and the average neurite length of hippocampal neuronal networks were strongly negatively correlated. Lidocaine hydrochloride (LC−HCl) and morphine hydrochloride (Mor−HCl) are two kinds of most prevalently used anesthetics. However, their influences on electrical excitability of hippocampal neuronal networks and hippocampal brain slices were rarely studied. Previously, our group have assessed the influence of acetylcholine, alcohol and temperature change on the excitability of neural networks with the so-called Voltage Threshold Measurement Method (VTMM) based on microelectrode array (MEA). In this paper, we will study the influence of LC−HCl and Mor−HCl on the electrical excitability of neural networks and the morphological features of neurons, and discuss the relations between the changes of electrical excitability of neural networks and the morphological changes of neurons. The results of VTMM showed: The voltage threshold (V Th) of hippocampal neuronal networks and hippocampal brain slices first increased and then decreased as the LC−HCl concentration increased. The V Th of hippocampal neuronal networks and hippocampal brain slices increased as the Mor−HCl concentration increased. The results of HCS experiments showed: The neurite length change of cultured hippocampal neuronal networks increased first and then decreased with increased LC−HCl concentration, but decreased as the Mor−HCl concentration increased. The combined analysis of VTMM and HCS experiments showed that under effects of the two drugs, the V Th and the hippocampal neurite length were strongly negatively correlated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Three green, simple, precise, accurate and sensitive spectrophotometric methods were developed for the determination of a binary mixture of lidocaine hydrochloride (LDC) and cetylpyridinium chloride (CPC) in the presence of dimethylaniline (DMA). In the three methods, the interference of DMA spectrum is eliminated using the ratio subtraction method. Method (A) depended on determining LDC and CPC by measuring the first derivative of the ratio spectra (1DD) at 271.0 and 268.4 nm, respectively. Method (B) was the ratio difference (RD), based on dividing the absorption spectrum of the binary mixture by a standard spectrum of CPC or LDC, then measuring the amplitude difference of the ratio spectra (∆P) between 231.2 and 240.0 nm for LDC and between 242.8 and 258.0 nm for CPC. Method (C) based on the application of dual wavelength coupled with the isoabsorptive point method. This was achieved by measuring the absorbance difference (∆A) between 243.0 and 268.6 nm for the determination of LDC, followed by application of isoabsorptive point method comprised of measurement the total content of the mixture of LDC and CPC at their isoabsorptive point at 240.0 nm. The content of CPC was obtained by subtraction. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of LDC and CPC in presence of DMA. The proposed methods displayed useful analytical characteristics for the determination of LDC and CPC in bulk powder and their combined dosage form. The obtained results were statistically compared with those obtained by the official methods, showing no significant difference with respect to accuracy and precision. Unlabelled Image • Three simple and eco-friendly spectrophotometric methods were successfully applied. • Analysis of a binary mixture in the presence of an impurity with overlapped spectra. • Validated according to the ICH guidelines & compared to the official methods. • The methods were applied for the analysis of dosage form without prior separation. • Easily implemented in QC labs lacking liquid chromatographic instruments. [ABSTRACT FROM AUTHOR]

• Ball-milling modified glutinous rice starch – chitosan composite films were fabricated and characterized for the first time. • Chitosan ratios affected the mechanical, swelling, erosion, and release behaviors significantly. • Permeation across porcine mucosa indicates the enhancement effect of chitosan. The fabrication and characterization of ball-milling modified glutinous rice starch (MGRS):chitosan (CS) composite films were demonstrated. Effect of CS ratios (2:1, 1:1, 1:2 MGRS:CS) on the film properties was investigated. Lidocaine hydrochloride was used as a model hydrophilic drug. ATR-FTIR confirmed hydrogen bond formation between MGRS and CS. XRD indicated an amorphous state of all fabricated films. The uniform and comparable thickness, weight, and drug contents of all fabricated films were obtained. The presence of CS did not affect the mucoadhesiveness of MGRS films. The increase in tensile strength and decreases in elongation and folding endurance were observed with 1:2 MGRS:CS films. The film swelling and drug release decreased with the CS ratio. Drug permeation across porcine mucosa indicated the enhancement effect of CS, whereby the permeation flux of 1:2 MGRS:CS composite increased by 3 folds. In conclusion, the MGRS:CS composite could be useful for buccal delivery of hydrophilic drug. [ABSTRACT FROM AUTHOR]

A chitosan-pectin (CS-PEC) biopolymeric hydrogel wound dressing was investigated for lidocaine delivery. Here we demonstrate for the first time the feasibility of three-dimensional (3D) printed CS-PEC hydrogel incorporating the local anaesthetic drug lidocaine hydrochloride (LDC) as a potential wound dressing candidate. The hydrogels were prepared by physical crosslinking of CS and PEC polysaccharides. The scaffolds were printed using an extrusion-based 3D printer using a mechanical positive displacement dispensing system followed by lyophilisation. The 3D printed hydrogels showed good printability, dimensional integrity and self-adhesion to skin. The high swelling ratio and water absorption of 3D printed hydrogels indicated suitability for absorbing exudates and maintaining a moist wound healing environment. Fourier transform infrared (FTIR) spectroscopy results indicated that the CS-PEC hydrogel was formed by hydrogen bonds. Incorporation of LDC in the hydrogel did not interfere with its functional stability. In vitro drug release studies of LDC over 6 h fitted the Korsmeyer-Peppas model. This work demonstrates the possibility of a 3D printed hydrogel as a suitable candidate for wound dressings. Unlabelled Image • A new 3D printing hydrogel ink based on pectin and chitosan can be used to develop tailor-made medicated wound dressings. • Lidocaine can be incorporated into the scaffold providing immediate pain relief. • The 3D printed hydrogels had good printability, dimensional integrity and adhesive properties. • The water absorption capacity of hydrogels are suitable for absorbing exudates and maintaining a moist environment. [ABSTRACT FROM AUTHOR]

Abstract: Lipid rafts have been implicated in the signaling processes. Anesthesia has been postulated to represent a transient, drug-induced interruption of signal transduction. In examining the effects of lidocaine on lipid rafts, we found that the agent abolished raft formation in a reversible manner in an erythrocyte membrane model. Our results suggested that raft-related signal transduction is involved in the anesthetic mechanism. [Copyright &y& Elsevier]