Deformability properties of timolol-loaded transfersomes based on the extrusion mechanism. Statistical optimization of the process.

The purpose of this work was to analyze the deformability properties of different timolol maleate (TM)-loaded transfersomes by extrusion. This was performed because elastic liposomes may contribute to the elevation of amount and rate of drug permeation through the corneal membrane. This paper describes the optimization of a transfersome formulation by use of Taguchi orthogonal experimental design and two different statistical analysis approaches were utilized. The amount of cholesterol (F1), the amount of edge-activator (F2), the distribution of the drug into the vesicle (F3), the addition of stearylamine (F4) and the type of edge-activator (F5) were selected as causal factors. The deformability index, the phosphorous recovery, the vesicle size, the polydispersity index, the zeta potential and percentage of drug entrapped were fixed as the dependent variables and these responses were evaluated for each formulation. Two different statistical analysis approaches were applied. The better statistical approach was determined by comparing their prediction errors, where regression analysis provided better optimized responses than marginal means. From the study, an optimized formulation of TM-loaded transfersomes was prepared and obtained for the proposed ophthalmic delivery for the treatment of open angle glaucoma. It was found that the lipid to surfactant ratio and type of surfactant are the main key factors for determining the flexibility of the bilayer of transfersomes. From in vitro permeation studies, we can conclude that TM-loaded transfersomes may enhance the corneal transmittance and improve the bioavailability of conventional TM delivery.

Surface functionalizing of a lipid nanosystem to promote brain targeting: step-by-step design and physico-chemical characterization.

The use of lipid nanosystems as drug delivery to the central nervous system may be advantageous over the current strategies. The aim of this study was to develop and characterize functionalized liposomes for treatment of brain diseases. The covalent method of coupling IgG to liposomes via the derivatized lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide](MPB-PE) was investigated. Optimized coupling conditions are shown to result in the efficient conjugation of IgG to liposomes containing low concentrations of MPB-PE (3/1 SH:IgG). The qualitative analysis has shown that after the extrusion process, more homogeneous populations of vesicles have been obtained with a nanometric size suitable to be effective to further anchor the protein. Negative values of zeta potential demonstrate that they are stable systems. Lyophilization was used to maintain the stability of the formulation. These very interesting results encourage further investigations to formulate peptide- and protein-loaded immunoliposomes, making targeting of liposomes as an attractive approach for brain drug delivery.

Molecularly imprinted polymer for selective determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid using LC-MS/MS in urine and oral fluid.

The use of molecularly imprinted polymers (MIPs) for solid phase extraction (MISPE) allows a rapid and selective extraction compared with traditional methods. Determination of Δ(9)-tetrahydrocannabinol (THC) and 11-nor-Δ(9)-tetrahydrocannabinol carboxylic acid (THC-COOH) in oral fluid (OF) and urine was performed using homemade MISPEs for sample clean-up and liquid chromatography tandem mass spectrometry (LC-MS/MS). Cylindrical MISPE shaped pills were synthesized using catechin as a mimic template. MISPEs were added to 0.5 mL OF or urine sample and sonicated 30 min for adsorption of analytes. For desorption, the MISPE was transfered to a clean tube, and sonicated for 15 min with 2 mL acetone:acetonitrile (3:1, v/v). The elution solvent was evaporated and reconstituted in mobile phase. Chromatographic separation was performed using a SunFire C18 (2.5 µm; 2.1 × 20 mm) column, and formic acid 0.1% and acetonitrile as mobile phase, with a total run time of 5 min. The method was fully validated including selectivity (no endogenous or exogenous interferences), linearity (1-500 ng/mL in OF, and 2.5-500 ng/mL in urine), limit of detection (0.75 and 1 ng/mL in OF and urine, respectively), imprecision (%CV <12.3%), accuracy (98.2-107.0% of target), extraction recovery (15.9-53.5%), process efficiency (10.1-46.2%), and matrix effect (<-55%). Analytes were stable for 72 h in the autosampler. Dilution 1:10 was assured in OF, and Quantisal™ matrix effect showed ion suppression (<-80.4%). The method was applied to the analysis of 20 OF and 11 urine specimens. This is the first method for determination of THC and THC-COOH in OF using MISPE technology.

Accuracy of working length measurement: electronic apex locator versus cone-beam computed tomography.

AIM: To compare the accuracy of working length (WL) determination using the Raypex 6(®) electronic apex locator and cone-beam computed tomography (CBCT). METHODOLOGY: A total of 150 extracted human teeth were decoronated and randomly assigned to five groups (n = 30). WL was measured with the Raypex 6(®) at both the 'constriction' and the 'apex' marks under dry conditions (group 1) or with 2.5% NaOCl, distilled water or Ultracain(®) (groups 2-4). The radiological WL (group 5) was calculated from bucco-lingual and mesio-distal CBCT sections. Differences between electronic, CBCT measurements and actual length (AL) were calculated. Positive and negative values, respectively, indicate measurements falling short or long of AL. Two-way anova and the Bonferroni and Welch tests were used to compare mean differences amongst groups. The chi-squared and Fisher's exact tests were used to compare percentages of precise, ±0.5 and ±1.0 mm of the AL measurements amongst the experimental groups. Statistical analysis was performed at α = 0.05. RESULTS: Mean differences with respect to AL ranged from 0.26 to -0.36 mm and from 0.05 to 0.18 mm, respectively, for the electronic measurements at the 'constriction' mark and 'apex' mark. CBCT measurements were an average of 0.59 mm shorter than AL. Percentages of electronic measurements falling within ±0.5 mm of the corresponding AL referred to the 'apex' mark were greater than at the 'constriction' mark, but the differences were only significant in group 4 (with Ultracain(®) ). Percentages of CBCT measurements falling within ±0.5 mm of AL (46.7%) were significantly lower than electronic measurements, regardless of the condition of the root canal. In 30-38.5% of the measurements taken at the 'apex' mark and in 3.4-13.3% of those at the 'constriction' mark, the file tip extended beyond the foramen. CONCLUSIONS: Electronic measurements were more reliable than CBCT scans for WL determination. The Raypex 6(®) was more accurate in locating the major foramen than the apical constriction under the experimental set-up.

Robust optimization of alginate-Carbopol 940 bead formulations.

Formulation process is a very complex activity which sometimes implicates taking decisions about parameters or variables to obtain the best results in a high variability or uncertainty context. Therefore, robust optimization tools can be very useful for obtaining high quality formulations. This paper proposes the optimization of different responses through the robust Taguchi method. Each response was evaluated like a noise variable, allowing the application of Taguchi techniques to obtain a response under the point of view of the signal to noise ratio. A L(18) Taguchi orthogonal array design was employed to investigate the effect of eight independent variables involved in the formulation of alginate-Carbopol beads. Responses evaluated were related to drug release profile from beads (t(50%) and AUC), swelling performance, encapsulation efficiency, shape and size parameters. Confirmation tests to verify the prediction model were carried out and the obtained results were very similar to those predicted in every profile. Results reveal that the robust optimization is a very useful approach that allows greater precision and accuracy to the desired value.

The impact of COVID-19 on European tourists' attitudes to air travel and the consequences for tourist destination evoked set formation.

We study how risk conditions derived from the COVID-19 pandemic may impact on both the desire to travel and intention to visit of tourists and, therefore, on different stages of the destination choice process. We analyse 5134 million flight searches and 379 million flight picks during 2020 for the 17 largest European tourism source markets. An unweighted index number is employed to measure the average variation for searches and picks, for the year 2020, in relation to the reference base period (year 2019). This is done for air travel in general and to Spain specifically. The study then proceeds to conduct an analysis of 17 international travel destinations that are in the evoked sets of the two largest outbound markets in Europe (Germany and UK). We also identify which markets are most favourable to Spain. The research design can inform cost-efficient marketing decisions in a situation of high uncertainty.

International air travel attitude and travel planning lead times across 45 countries in response to the COVID-19 pandemic.

This paper explores global differences in travel risk perception based on i) attitudes towards travel abroad, and ii) the time required to plan travel. Baseline data from 2019 is compared with data from 2020, the first year of the COVID-19 pandemic. A methodology based on Big Data is developed through the Skyscanner metasearch engine, working with 20,756 million flight searches and 1979 million flight picks worldwide. We conduct an exploratory analysis by region, followed by a cluster analysis of 45 countries. We argue that the findings respond to uncertainty avoidance, with clear differences between Europe, America and Asia-Pacific. This knowledge has marketing implications for tourist destinations in terms of what marketing messages to convey and the best time to introduce marketing campaigns for each country or group of countries, so that the opportunity for reactivation of tourism is maximised.

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

Dissolving efficacy of eucalyptus and orange oil, xylol and chloroform solvents on different root canal sealers.

AIM: To evaluate the solubility of five root canal sealers in orange oil, eucalyptol, xylol and chloroform solvents. METHODOLOGY: The solubility of RoekoSeal, Sealer 26, Epiphany, Endomethasone and EZ-Fill sealers was assessed in orange oil, eucalyptol, xylol, chloroform and distilled water. Seventy-five samples of root canal sealers were prepared and then divided into five groups for immersion in solvent for 2, 5 or 10 min. The means of loss weight were determined for each material in each solvent at all immersion periods, and the values were compared by factorial analysis of variance (anova) and SNK multiple comparisons. RESULTS: In the orange and eucalyptus oil groups, there was no significant difference among RoekoSeal, Sealer26, Epiphany and EZ-Fill at the three immersion periods (P > 0.05). With xylol, no significant differences were found at 5 and 10 min (P > 0.05) for each root sealer. Orange and eucalyptus oil solvents were as effective as chloroform at 2 min in dissolving all the root sealers. CONCLUSIONS: Xylol was the most effective solvent followed by the chloroform and the essential oils (eucalyptol and orange oil). Orange oil behaved in a similar way to eucalyptus oil.

Early versus conventional nutritional intervention in head and neck cancer patients before radiotherapy: benefits of a fast-track circuit.

BACKGROUND/OBJECTIVES: Radiotherapy (RT) is a component of therapy for head and neck cancer (HNC) with a negative nutritional impact. Our aim was to compare an early versus a conventional nutritional intervention. SUBJECTS AND METHODS: Retrospective study of HNC patients undergoing RT. Evolution before and after the establishment of a fast-track circuit was evaluated. A conventional group (CG) made up of patients submitted to the nutrition unit during RT after nutritional deterioration, was compared to an early group (EG) represented by patients included in a fast-track circuit, starting nutritional follow-up before the beginning of RT. Only patients with preserved oral intake were involved. Demographic, nutritional and clinical variables were analyzed. Data of hospitalizations and deaths were collected up to three months after RT. RESULTS: 135 subjects constituted the EG and 39 the CG. At baseline, the prevalence of malnutrition was lower in the EG (31.9% vs 69.5%, p = 0.0001), as was the need for nutritional supplements (40% vs 79.5%, p = 0.0001) or nasogastric tube (0% vs 12.8%, p = 0.0001) in comparison to the CG. Three months after RT, there were less patients with oral nutritional support in the EG (79.1% vs 96.9%, p = 0.018), and the number of emergency visits (0.75 vs 1.1 episodes per patient, p = 0.021) and hospitalizations was also lower in this group (29% vs 59%, p = 0.044). CONCLUSIONS: The fast-track approach made early intervention possible. Therefore, patients maintained a better nutritional status, needed less nutritional support and their evolution improved, with a significant decrease in hospitalizations.

Liquid chromatographic methods to analyze hindered amines light stabilizers (HALS) levels to improve safety in polyolefins.

A chromatographic method using ultra performance LC with ultraviolet spectrophotometry detection system (UPLC-UV-visible (UV/Vis)) (UPLC, ultra performance LC) was developed to determine Chimassorb 944 and Tinuvin 770, high- and low-molecular mass hindered amine light stabilizers, respectively. The use of a bridge ethylene hybrid-based particles C(18) UPLC column, being compatible with a buffered mobile phase adjusted to pH 11.5, was used to achieve a satisfactory elution of possible non-ionizated units of polymeric Chimassorb 944. In addition, a HPLC with positive ion mode ESI and hybrid linear ion trap (LTQ) Fourier transform (FT) Orbitrap MS detection system (HPLC-UV/Vis-ESI-LTQ(FT)Orbitrap) was used for screening and identification purposes. Reliable determinations of monomeric units of Chimassorb 944 and molecule of Tinuvin 770 were achieved by HPLC-ESI(+)-LTQ FT Orbitrap MS method using scan mode. Quality parameters of UPLC-UV/Vis method were evaluated. Obtained LODs and LOQs were 3.41 and 11.4 mg/L for Tinuvin 770 and 0.83 and 2.78 mg/L for Chimassorb 944, respectively. Satisfactory quality parameters of this chromatography method provided the chance to count on a good tool to know the compliance with legal requirements.

Application of liquid chromatography in polymer non-ionic antistatic additives analysis.

This article investigates the applicability of HPLC-UV, ultra performance LC-evaporative light-scattering detection (UPLC-ELSD), HPLC-ESI(+)-MS and HPLC-hybrid linear ion trap (LTQ) Orbitrap MS for the analysis of different non-ionic antistatic additives, Span 20, Span 60, Span 65, Span 80, Span 85 (sorbitan fatty acid esters), Atmer 129 (glycerol fatty acid ester) and Atmer 163 (ethoxylated alkylamine). Several alkyl chain length or different degrees of esterification of polyol derivatives can be present in commercial mixtures of these polymer additives. Therefore, their identification and quantification is complicated. Qualitative composition of the studied compounds was analysed by MS. HPLC-UV, UPLC-ELSD and HPLC-LTQ Orbitrap MS methods were applied to the quantitative determination of the different Spans, Atmer 129 and Atmer 163, respectively. Quality parameters of these methods were established and no derivatization was necessary.

Positively and negatively charged liposomes as carriers for transdermal delivery of sumatriptan: in vitro characterization.

BACKGROUND: The influence of liposome composition, lamellarity, preparation method, and charge on the encapsulation efficiency, size, polydispersity, and surface charge of sumatriptan liposomes was studied. For this purpose, we studied multilamellar, unilamellar, and frozen and thawed liposomes. Positively or negatively charged liposomes were obtained using both phosphatidylcholine and cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal formulations were characterized by confocal laser scanning microscopy and optical microscopy for vesicle formation, morphology, and lamellarity by dynamic laser light scattering for size distribution and polydispersity, and electrophoretic mobility for zeta potential determination. To obtain more information about the sumatriptan encapsulation, dynamic dialysis technique was employed. The sumatriptan amount was quantified by high-performance liquid chromatography. RESULTS: Overall obtained results showed that liposomes may be interesting carriers for sumatriptan succinate. Statistical analysis evidenced that the preparation method does not affect the evaluated characterization parameters. However, the presence of charge inducer agents modified these characteristics. Highest loading efficiency of sumatriptan was exhibited for positively charged liposomes containing 6.58:10.34:3.73 mmolar ratio for phosphatidylcholine : cholesterol : stearylamine. The mean size was affected by the charge inducer, being smaller in positively charged liposomes. Logically, surface charge of liposomes varied as a function of the employed charged agent. Also, interesting results were obtained when vesicles were loaded with sumatriptan, showing a statistical significance between all pairs, comparing the formulations with and without drug. CONCLUSION: Results obtained revealed that the presence of sumatriptan into the vesicles has a different behavior in negatively and positively charged liposomes.

Topographical evaluation of the major apical foramen in permanent human teeth.

AIM: To determine the distance from the anatomical root apex to the major apical foramen and the position of the major foramen on the root apex. METHODOLOGY: Crowns of 926 human teeth were sectioned at the cementum-enamel junction. Specimens were mounted on microscope slides for measurement parallel to the long axis of the teeth. The major foramen was identified as the largest-diameter opening at the root apex. A total of 1331 root specimens were evaluated using an optical stereomicroscope to an accuracy of 0.01 mm at 40 x (+/-10) magnification. The distance from the anatomical apex to the most apical point of the major foramen was measured, and its location (central, buccal, lingual, mesial and distal) was recorded. RESULTS: The mean distance between the major foramen and the anatomical root apex was 0.69 mm; the mean distance was larger in posterior teeth (0.82 mm) and smaller in anterior teeth (0.39 mm). A wide range of anatomical apex to major foramen distances were observed in all tooth groups: the greatest distance was in maxillary molars (0.95 mm) followed by mandibular pre-molars (0.87 mm) and mandibular molars (0.80 mm). The major foramen was at the tip of the root in 40% of teeth. The most frequent deviations of the foramen were to the buccal (20%) and distal (14%). CONCLUSION: In this sample of teeth without apical resorption the distance between the major foramen and the anatomical root apex was always <1 mm. Deviation of the major foramen from the anatomic apex varied widely amongst tooth groups.

A zinc oxide-modified hydroxyapatite-based cement favored sealing ability in endodontically treated teeth.

OBJECTIVES: To evaluate the effectiveness of different endodontic canal sealers for dentin permeability reduction and to determine the viscoelastic performance of root dentin after their application. METHODS: Cervical, medial and apical root dentin surfaces were treated with two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite); an epoxy resin- based canal sealer, AH Plus; and gutta-percha. Root dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM, Young's modulus and Nano-DMA analysis were also performed, at the inner and outer zones of dentin. RESULTS: Dentin treated with oxipatite showed the lowest microleakage among groups with hermetically sealed tubules and zinc-based salt formations. Samples treated with oxipatite showed the highest Ei at the cervical dentin third among groups, at 6 m of storage. Oxipatite promoted the highest complex modulus and tan delta values at the inner zone of both cervical and medial root dentin. Calcypatite favored the lowest tan delta outcomes at the inner zone of apical dentin at 6 m. CONCLUSIONS: Specimens treated with oxipatite showed the highest sealing ability, based on the highest Young's modulus and dentin mineralization, achieved by closing dentinal tubules, voids and pores that reinforced the inner zone of root dentin. The homogeneity of viscoelastic properties among the different root dentin thirds favored the energy dissipation without creating zones of stress concentration and micro-cracking which would have challenge micropermeability. Thereby, among the tested materials oxipatite is proposed as canal filling material and sealer in endodontics. CLINICAL SIGNIFICANCE: Oxipatite could be considered a good candidate for root canal filling material and sealer due to its improved long-term sealing ability and to the advanced remineralization, and so to the enhanced energy dissipation achieved at the inner zone of the radicular dentin.

Combination of thoracic blocks as a main anesthetic tecnique in modified radical mastectomy for patients with severe respiratory disease. / Combinación de bloqueos torácicos como método anestésico principal en mastectomía radical modificada para pacientes con compromiso respiratorio severo.

The addition of ultrasound to locoregional anaesthesia in the last few years has led to the description of various fascial thoracic blocks with analgesic purposes: PECS 1 and 2 block, serratus plane block, serratus intercostal fascial block, blockade in the plane of the thoracic transverse muscle..., which have been added to other well-known nerve blocks, such as thoracic paravertebral block or intercostal block. In this sense, locoregional anaesthesia has been universally recommended in patients with severe respiratory processes in order to avoid ventilatory support and subsequent weaning that considerably increases postoperative morbidity and mortality rates. However, as regards thoracic wall and axillary hollow, there are very few references which detail the use of nerve or fascial blocks as a main anaesthetic method. Two extreme cases are presented of multi-pathological patients with serious respiratory disease who successfully underwent a modified radical mastectomy plus surgery in the axillary space using a combination of ultrasound-guided thoracic blocks that allowed surgery without general anaesthesia, avoiding mechanical ventilation, and maintaining spontaneous breathing throughout the surgical procedure. The main indications of the anaesthetic blocks used are described, focusing on the performance of the technique and underlining, in a novel way, the possibility of facing aggressive surgery at the level of the armpit with only locoregional anaesthesia.

High-performance liquid chromatography analysis of ten dyes for control of safety of commercial articles.

Two high-performance liquid chromatographic methods, with ultraviolet-visible spectrophotometry detection (HPLC-UV/Vis) and with tandem mass spectrometry triple quadrupole interfaced with positive ion mode electrospray ionization detection (HPLC-ESI+-QqQ-MS/MS), for determination and quantification of ten commercial dyes are proposed for control in commercial products. Multiple peaks observed for some of the studied dyes in HPLC-UV/Vis chromatograms forced to obtain structural information by HPLC-ESI-MS/MS method with scan mode. The quality parameters of the two proposed chromatographic methods were evaluated for different requirements of normative, showing detection (LODs) and quantification (LOQs) limits around 60-890 and 200-2990 microg L(-1) for HPLC-UV/Vis, and 4.54-14.3 and 15.0-47.6 microg L(-1) for HPLC-ESI+-QqQ-MS/MS.

Wet granulation as innovative and fast method to prepare controlled release granules based on an ion-exchange resin.

The goal of this work was to evaluate the suitability of wet granulation as an innovative and fast method for the preparation of granules containing a drug-resin complex (resinate), having cholestyramine as resin and potassium diclofenac (KD) as drug. Resinate and granules were prepared directly by steam granulation in high shear mixer (method A), using two different amount of resin (granules 1 and 2). For comparison granules 1 were also prepared by conventional batch method followed by steam granulation (method B). All granules showed quite irregular shape, main size fractions between 75 and 500 microm, good flowability and uniform KD distribution. Granules 1A exhibited controlled release profiles at pH 7.4, while granules 2A showed a burst effect due to KD free crystals. FT-IR studies confirmed the complete complexation between resin and KD during the granulation process with method A for granules 1. Finally, the dissolution test of granules 1A in different media revealed a controlled drug release in 12 h, providing the utility of this system for enteric drug delivery. Granules 1B evidenced similar characteristics to those of granules 1A; the drawback of the multistep procedure was related to the long processing time.

Development and validation of a reverse-phase liquid chromatographic method for the assay of lidocaine hydrochloride in alginate-Gantrez microspheres.

A simple, fast and reliable reverse-phase high-performance liquid chromatographic (HPLC) method was developed for the assay of lidocaine hydrochloride (LH) in Gantrez-alginate microspheres. Separation was achieved in a LiChrospher C18 column, using a mobile phase consisting of acetonitrile:ammonium acetate (0.0257 M) adjusted to pH 4.85 with acetic acid, in the ratio 70:30 (v/v) and a flow rate of 0.6 mL/min. The detection was made with a diode array detector measuring at the maximum for the compound. The validation study demonstrated that the method was precise, accurate and linear over the concentration range of analysis with a limit of detection of 0.001 mg/mL. The limit of quantification was 0.002 mg/mL. Linear regression analysis in the range of 0.8-2.4 mg/mL gave correlation coefficients higher than 0.995. The method developed was applied to the analysis of lidocaine in microsphere samples in order to evaluate in next papers, the encapsulation efficiency of different formulations.

Decalcifying effect of 15% EDTA, 15% citric acid, 5% phosphoric acid and 2.5% sodium hypochlorite on root canal dentine.

AIM: To evaluate and compare ex vivo the decalcifying effect of 15% EDTA, 15% citric acid, 5% phosphoric acid and 2.5% sodium hypochlorite on root canal dentine. METHODOLOGY: Two 2-mm-thick slices were cut from the coronal third of the root of 10 human incisors. Each slice was sectioned into two equal parts. Specimens were assigned to one of four groups (n = 10) for immersion in 20 mL of either 15% EDTA, or 15% citric acid, 5% phosphoric acid or 2.5% NaOCl, for three time periods (5, 10 and 15 min). The concentration of Ca(2+) extracted from the dentine was measured by atomic absorption spectrophometry. The amount of calcium extracted was analysed using the Kruskal-Wallis test for global comparisons and the Mann-Whitney U-test for pairwise comparisons. RESULTS: In the three time periods, 15% EDTA and 15% citric acid extracted the largest amount of calcium, with no significant differences between them. The 2.5% NaOCl solution extracted insignificant amounts of calcium, whereas 15% EDTA extracted 86.72% of the calcium in the first 5 min, and 15% citric acid and 5% phosphoric acid had a similar pattern of calcium removal (77.03% and 67.08% in first 5 min, respectively). CONCLUSIONS: Solutions of 15% EDTA, 15% citric acid and 5% phosphoric acid decalcify root dentine, with most calcium extracted during the first 5 min of action. The efficacy of 15% citric acid and 15% EDTA solutions was significantly greater than that of 5% phosphoric acid solution at each time period (5, 10 and 15 min).