Biomechanical considerations on macromorphology of endosseous dental implants.

The aim of the present study is to define the optimal thread form and why the macroscopic shape of the dental intra-osseous implant interacts with the biological environment thus conditioning its lifespan and long-term success.

Static and fatigue resistance of two types of implant/abutment connectors.

The aim of this study is to determine in an experimental way through mechanical tests the static, fatigue and torque resistance of two types of implant/abutment connectors with diameters of 3.4–5.2 mm.

Instant loading with intraoral welding technique and PRAMA implants: a new prosthetic approach.

When splinting multiple implants passive fit of the framework should be achieved to avoid excessive force distribution on the implants. Recently, a protocol was suggested for immediate loading of multiple implants by welding a titanium bar to implant abutments directly in the oral cavity so as to create a customized, precise and passive metal-reinforced provisional restoration. The intraoral welding technique subsequently proves to be a successful option in the full-arch immediate restorations of the mandible and maxilla. The aim of this article is to present a case report in which a new prosthetic approach, using trans-mucosal implants, is described. Dental implants are instantly loaded with a provisional prosthesis supported by an intraoral welded titanium framework to obtain a precise passive fit of the immediate loaded prosthesis.

The importance of immediately loaded immediate post-extractive implants in esthetical rehabilitation: case series.

The aim of this paper was to estimate, in a retrospective way, integration of hard and soft tissues in immediately loaded immediate postextractive implants. Benefits of this technique could be: single stage surgery, biological saving of tissues, aesthetic management of edentulism, good integration of both hard and soft tissues. Immediate loading of a postextractive implant seems also to produce a positive effect on the quality of perimplant soft tissues. The implants used in the present study have some advantages such as high auto-threading and auto-tapping ability, progressive increase of the thickness of the threads, at the apical and coronal level. All these features have helped to obtain a high primary stability.

Capillary electrophoretic analysis of the antibiotic vancomycin in innovative microparticles and in commercial formulations.

A new fast capillary electrophoretic method has been developed for the analysis of the glycopeptide antibiotic vancomycin in formulations. An electrophoretic run is completed within 3.0 min; fused silica capillaries (100 microm i.d., 8.5 cm effective length and 48.5 cm total length) and a background electrolyte consisting of 12.5 mM, pH 2.5 phosphate buffer are used. The applied voltage is -20.0 kV; samples are injected by pressure (30 mbar x 3 s) at the anodic end of the capillary. The method was successfully applied to innovative controlled release microparticles consisting of a coated albumin core containing vancomycin. A simple procedure has been developed to obtain complete vancomycin extraction from microparticles using a 5% (w/v) sodium dodecyl sulphate aqueous solution. The method has been validated in terms of linearity, precision and accuracy. Good linearity was found in the 0.25-5.00 microg/mL range. Satisfactory precision was obtained, with relative standard deviation values always lower than 3.9%; accuracy was satisfactory, with recovery values between 97.8 and 102.2%. The method is also suitable for vancomycin determination in commercial capsules.

Use of vancomycin chiral stationary phase for the enantiomeric resolution of basic and acidic compounds by nano-liquid chromatography.

In this paper we studied the potentiality of nano-liquid chromatography (nano-LC) for the enantiomeric resolution of both basic and acidic compounds of pharmaceutical interest using a vancomycin modified silica stationary phase. Experiments were carried out in a fused silica capillary of 75 microm I.D. packed with chiral modified silica particles of 5 microm diameter, the detection, was done on-line at 195 nm. Enantiomeric resolution of alprenolol, atenolol, metoprolol, oxprenolol, pindolol, propranolol (basic compounds) and some acidic analytes, namely 2-[(5'-benzoyl-2'-hydroxy)phenyl]propionic acid (DF1738Y), 2-[(4'-benzoyloxy-2'-hydroxy)phenyl]propionic acid (DF1770Y), ketoprofen, indoprofen and suprofen was studied by nano-LC utilizing mobile phases containing methanol-acetonitrile-ammonium formate or acetate. The effect of mobile phase composition (buffer type and concentration, organic modifier type and concentration) on chiral resolution (Rs), retention factor (k) and retention time (tR) was also investigated. Good enantiomeric resolution was achieved for basic compounds utilizing the mobile phase containing 90% (MeCN-MeOH)/5% water/5% of 100 mM ammonium acetate pH 4.5. Acidic compounds such as DF1738Y and DF1770Y were better resolved at lower pH 3.5 while ketoprofen, indoprofen and suprofen exhibited the highest resolution at pH 4.5; in this case the mobile phase contained MeOH or MeCN (90%), 5% buffer and 5% of water. The nano-LC method was validated using R-(+)-propranolol as an internal standard finding good repeatability, detection limit, correlation coefficient and recovery and applied to the assay of a pharmaceutical formulation containing a racemic mixture of metoprolol.

Direct determination by capillary electrophoresis of cardiovascular drugs, previously included in liposomes.

The lipophilicity of some cardiovascular drugs was determined by capillary electrophoresis (CE). Mexiletine, amlodipine and indapamide, the drugs considered, were in contact with liposomial vescicles for 2, 4 or 6 h. After the contact time the drugs, penetrated into liposomial vesicles, were determined by CE using phosphate buffer (pH 6.3 or 7.4) or borate buffer (pH 9). The lipophilicity of three drugs was determined considering the drug percentage penetrated into liposomial vesicles. The found lipohilicity order was amlodipine > mexiletine > indapamide.

Analysis of diltiazem and its related substances by HPLC and HPLC/MS.

Diltiazem (DTZ) is an optically active calcium channel blocker having a benzodiazepine structure. The drug used in therapy is (+)-cis-diltiazem with configuration (2S,3S). To describe the analytical profile of DTZ different stationary phases (RP-18, RP-8, monolithic support) were tested. The best separation of DTZ from A, B, E and F was obtained using as stationary phase a RP-8 or a monolithic RP-18. The characterization of impurities was carried out using two analytical systems, HPLC and HPLC/MS.

Micellar electrokinetic chromatography for determination of drug partition in phospholipids.

The lipophilicity of pipemidic, nalidixic and oxolinic acids was determined by forming phospholipidic micelles directly in an electrophoretic capillary. Phosphatidylcholine derivatives, namely L-alpha-dilauroyl phosphatidylcholine (DLPC) or L-alpha-dimiristoyl phosphatidylcholine (DMPC), were added in the run buffer (50 mM phosphate buffer at pH 7.4). To obtain a mixed micelle, phospholipidic derivatives and sodium cholate were together added in the run buffer. Considering the increasing of migration time when phosphatidylcholine derivative is added in the run buffer, Ks can be determined and then quinolones lipophilicity.

Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors.

This review surveys the separation of enantiomers by capillary electrophoresis using cyclodextrins as chiral selector. Cyclodextrins or their derivatives have been widely employed for the direct chiral resolution of a wide number of enantiomers, mainly of pharmaceutical interest, selected examples are reported in the tables. For method optimisation, several parameters influencing the enantioresolution, e.g., cyclodextrin type and concentration, buffer pH and composition, presence of organic solvents or complexing additives in the buffer were considered and discussed. Finally, selected applications to real samples such as pharmaceutical formulations, biological and medical samples are also discussed.

Identification of chiral drug isomers by capillary electrophoresis.

Separation of optical isomers of compounds of pharmaceutical interest by capillary electrophoretic techniques is reviewed. The direct and indirect separation method, as well as the main resolution mechanisms and the parameters influencing the stereoselectivity are discussed considering capillary zone electrophoresis, micellar electrokinetic chromatography, isotachophoresis and electrochromatography. Several chiral selectors have been successfully used in CE for chiral separation, including cyclodextrins and their derivatives, modified crown-ethers, proteins, antibiotics, linear saccharides and chiral surfactants. Only applications in the pharmaceutical field with the most important experimental conditions are summarised in the Tables reported in this paper. The chiral analyses of drugs in real samples like biological fluids or pharmaceutical formulations are also reported.

Controlling enantioselectivity in chiral capillary electrophoresis with inclusion-complexation.

The separation of chiral compounds is of key importance in different fields of application, e.g., pharmaceutical, industrial, forensic, biological, clinical etc. Capillary electrophoresis (CE) is a powerful analytical method applied in chiral analysis and inclusion-complexation is one of the most frequently used mechanism to improve the selectivity of the enantiomeric separation. Cyclodextrins and their derivatives or modified crown-ethers have been successfully applied in CE for the enantiomeric separation of a wide number of analytes. This review surveys the separation of enantiomers by CE when chiral selectors, forming inclusion-complexation, are used. The control of enantioselectivity can be done carefully by considering several experimental parameters such as chiral selector type and concentration, pH, ionic strength and concentration of the background electrolyte, electroosmotic flow, organic modifier etc. The review presents a list of the latest separation of enantiomers by CE where inclusion-complexation plays a key role in the stereoselective separation mechanism.

Chiral analysis by capillary electrophoresis using antibiotics as chiral selector.

The separation of chiral compounds by capillary electrophoresis (CE) is a very interesting field of research in different areas such as pharmaceutical, environmental, agricultural analysis etc. The separation of two enantiomers can be achieved in CE using a chiral environment interacting with the two analytes on forming diastereoisomers with different stability constants and thus different mobilities. A wide number of chiral selectors have been employed in CE and among them glycopeptide antibiotics exhibited excellent enantioselective properties towards a wide number of racemic compounds. Vancomycin, ristocetin A, rifamycins, teicoplanin, kanamycin, streptomycin, fradiomycin, and two vancomycin analogues, added to the background electrolyte (BGE), are the antibiotics studied by CE running the separation in untreated and/or coated fused-silica capillary. Due to adsorption and absorption phenomena, some drawbacks can be expected when using bare fused-silica capillary, e.g., changes of electroosmotic flow (EOF), broaden peaks, reduced efficiency and low sensitivity. Coated capillary and counter current mode can be the solution to overcome the above mentioned problems. This review surveys the separation of enantiomers by CE when macrocyclic antibiotics are used as chiral selector. The enantioselectivity can be easily controlled modifying several parameters such as antibiotic type and concentration, pH, ionic strength and concentration of the background electrolyte, organic modifier etc. The paper also presents a list of the latest chiral separations achieved by CE where antibiotics were used as chiral selector.

Capillary electrochromatography and capillary electrochromatography-electrospray mass spectrometry for the separation of non-steroidal anti-inflammatory drugs.

In this study capillary electrochromatography (CEC) was utilized for the separation of ten non-steroidal anti-inflammatory drugs (NSAIDs). Experiments were carried out in a commercially available CE instrument using a packed capillary with RP-18 silica particles where the stationary phase completely filled the capillary. The mobile phase consisted of a mixture of ammonium formate buffer pH 2.5 and acetonitrile. Selectivity and resolution were studied changing the pH and the concentration of the buffer, the acetonitrile content mobile phase and the capillary temperature. The optimum experimental conditions for CEC separation of the studied drug mixture were found using 50 mM ammonium formate pH 2.5-acetonitrile (40:60) at 25 degrees C. The CEC capillary was coupled to an electrospray mass spectrometer for the characterization of the NSAIDs. A mobile phase composed by the same buffer but with a higher concentration of acetonitrile (90%) was used in order to speed up the separation of analytes.

Analysis of hydroquinone and some of its ethers by using capillary electrochromatography.

Capillary electrochromatography (CEC) was used for the analysis of relevant compounds in cosmetic preparation. Hydroquinone (HQ) and some of its ethers (methyl-, dimethyl-, benzyl-, phenyl-, propyl-HQ derivatives) were analyzed by using an octadecylsilica (ODS) stationary phase packed in fused-silica capillary (100 microm I.D.; 30 cm and 21.5 cm total and effective lengths, respectively). 20 mM Ammonium acetate pH 6-acetonitrile (50-70%) were the mobile phases used for the experiments. The acetonitrile (ACN) content strongly influenced the resolution of the studied compounds as well as the efficiency and the retention factor. Baseline resolution for the studied analytes was achieved at both the lowest and the highest percentage of ACN, the last one providing the shortest analysis time. Mobile phase containing 70% of ACN was therefore used for the analysis of an extract of skin-toning cream declared to contain HQ. Good repeatability of both retention times, peak areas and peak areas ratio (Asample/Ainternational standard) was found. The calibration graphs were linear in the concentration range studied (5-90 microg/ml) with correlation coefficients between 0.9975 and 09991. The analysis of the cosmetic preparation revealed the presence of HQ (1.72%, w/w) and of two additional peaks (not identified).

Capillary zone electrophoresis separations of enantiomers present in complex ionic matrices with on-line isotachophoretic sample pretreatment.

Analytical capabilities of capillary zone electrophoresis (CZE) with on-line coupled capillary isotachophoresis (ITP) sample pretreatment in the column-coupling capillary electrophoresis equipment to separate and determine enantiomers present in multicomponent ionic matrices were studied. Tryptophan was used as a model analyte in the ITP-capillary zone electrophoresis experiments performed in this context while a 90-component model mixture of UV-light absorbing organic anions and urine served as multicomponent sample matrices. Various working modes in which the on-line coupled capillary isotachophoresis-capillary zone electrophoresis combination in the column-coupling separation system can operate were employed in the anionic regime of the separation with direct injections of the samples. Advantages and limitations of these working modes in the separations of enantiomers present in model and urine matrices were assessed. Experiments with model mixtures of tryptophan enantiomers revealed that the two were resolved in the capillary zone electrophoresis stage with the aid of alpha-cyclodextrin also when their concentration ratio in the sample was 1:200 while the concentration of L(-)-tryptophan was 25 nmol/l. The limits of detection for the enantiomers were at approximately 10 nmol/l (approximately 1.5 ng/ml) concentrations for a 220 nm detection wavelength of the UV detector employed in the capillary zone electrophoresis stage and for a 30 microliters sample load. A high sample load capacity of the on-line coupled capillary isotachophoresis stage was effective in separating the samples corresponding to 3-6 microliters volumes of undiluted urine. The results from the runs with urine samples showed that only the capillary isotachophoresis-capillary zone electrophoresis combination with a post-column on-line coupled capillary isotachophoresis sample clean-up (responsible for a removal of more than 99% of the sample anionic constituents migrating in the on-line coupled capillary isotachophoresis stack and detectable in the capillary zone electrophoresis stage) provided a universal alternative for the detection and quantitation of the model analyte (L(-)-tryptophan).

Micellar electrokinetic chromatography for the simultaneous determination of ketorolac tromethamine and its impurities. Multivariate optimization and validation.

A simple, fast and selective micellar electrokinetic chromatographic (MEKC) method for the simultaneous assay of ketorolac tromethamine and its known related impurities (1-hydroxy analog of ketorolac, 1-keto analog of ketorolac and decarboxylated ketorolac), in both drug substance and coated tablets, is described. The compounds were detected at 323 nm, and flufenamic acid (FL) and tolmetin (TL) were chosen as internal standards to quantify ketorolac tromethamine and impurities, respectively. The multivariate optimization of the experimental conditions was carried out by means of the response surface study, considering as responses the resolution values and analysis time. The optimized background electrolyte (BGE) consisted of a mixture of 13 mM boric acid and phosphoric acid, adjusted to pH 9.1 with 1 M sodium hydroxide, containing 73 mM sodium dodecyl sulfate (SDS). Optimal temperature and voltage were 30 degrees C and 27 kV. Applying these conditions, all compounds were resolved in about 6 min. The related substances could be quantified up to the 0.1% (w/w) level. Validation was performed, either for drug substances and drug product, evaluating selectivity, robustness, linearity and range, precision, accuracy, detection and quantitation limits and system suitability.

Use of vancomycin silica stationary phase in packed capillary electrochromatography. II. Enantiomer separation of venlafaxine and O-desmethylvenlafaxine in human plasma.

A capillary electrochromatography method, using vancomycin chiral stationary phase packed capillary, was optimized for the simultaneous chiral separation of the antidepressant drug venlafaxine and its main active metabolite O-desmethylvenlafaxine. Simultaneous baseline enantiomeric separation of the two compounds was obtained using a mobile phase composed of 100 mM ammonium acetate buffer pH 6/water/acetonitrile (5:5:90, v/v). The electrokinetic injection for sample introduction provided a limit of quantitation for both the compounds of 0.05 microg/ml racemate concentration suitable for the analysis of venlafaxine and metabolite in biological samples. The acetonitrile mobile phase concentration was found to modulate the analytes elution times, the enantiomeric resolution and the efficiency of the separation. The column was tested for repeatability and linearity showing RSD values (%) in the range of 0.13-0.24, 2.47-3.66 and 1.35-2.50 for migration time, sample/internal standard peak area ratio and enantiomeric resolution, respectively and correlation coefficients higher than 0.9990. The method was applied to the analysis of clinical samples of patients under depression therapy showing a stereoselective metabolism for venlafaxine.

Simultaneous stereoselective analysis by capillary electrophoresis of tramadol enantiomers and their main phase I metabolites in urine.

Capillary zone electrophoresis was successfully applied to the enantiomeric resolution of racemic tramadol and its six phase I metabolites using carboxymethylated beta-cyclodextrin (CMB) added to the background electrolyte (BGE). Baseline resolution of tramadol and its metabolites was obtained in less than 30 min using a 50 mM phosphate buffer (pH 2.5) containing 5 mM of CMB. Chiral determinations of tramadol and its main three metabolites, O-demethyltramadol (M1), N-demethyltramadol (M2) and O-demethyl-N-demethyltramadol (M5), were performed in urine after a simple double liquid-liquid extraction of 200 microliters of biological material. In the tested concentration range (0.5-20 micrograms/ml, except for M2: 0.5-10 micrograms/ml) coefficients of correlation superior than 0.994 were obtained. Within-day variation determined on three different concentrations for each enantiomers showed accuracies ranging from 95.4% to 103.2%. The relative standard deviation (RSD) of these assays was determined to be less than 10.0%. Day-to-day variation presented accuracies ranging from 96.3% to 106.5% with a RSD less than 9.0%. After oral administration of 100 mg of tramadol hydrochloride to an healthy volunteer, the urinary excretion was monitored during 30 h. About 15% of the dose was excreted as unchanged tramadol. The enantiomeric ratios of all the excreted analytes, T, M1, M2 and M5, were found to be very different to 1.0, showing that a stereoselective metabolism of tramadol clearly occurred.

Simultaneous stereoselective analysis of tramadol and its main phase I metabolites by on-line capillary zone electrophoresis-electrospray ionization mass spectrometry.

On-line combination of partial filling capillary electrophoresis and electrospray ionization mass spectrometry was demonstrated for the simultaneous enantioseparation of tramadol and its main phase I metabolites. The partial filling technique was efficient at avoiding MS contamination by the chiral selector. Different experimental factors were investigated, including the chiral selector nature and concentration, plug length as well as the separation temperature. The best enantioseparation of the investigated compounds was achieved with a coated polyvinyl alcohol capillary and a 40 mM ammonium acetate buffer, pH 4.0, adding sulfobutyl ether beta-cyclodextrin (2.5 mg/ml) as the chiral selector. The charged cyclodextrin not only allowed enantioseparation of tramadol and its metabolites, but also improved the selectivity of compounds with the same molecular mass. Finally, CE-electrospray ionisation-MS was successfully applied to the stereoselective analysis of tramadol and its main metabolites in plasma after a simple liquid-liquid extraction.