Biomedical subjects

A Fini

Publications and source records attributed to A Fini.

At least 19 recordsLinked to original sources

PubMed2001

Improvement of the synthesis of diphenylmethyl 7beta-(o-hydroxy)benzylideneamino-3-hydroxymethyl-3-cephem-4-carboxylate.

The title product (I) is synthesized currently from 7-aminocephalosporanic acid, and diphenyldiazomethane (DDM) is used as a protective reagent of the acid function for further reactions. When DDM was prepared from benzophenone hydrazone by reaction with chloramine T, it was resulted impure by p-toluenesulfonamide, formed as side product, which cannot be removed during the final purification step carried out according to the literature procedure. Two simple methods are proposed here to obtain I with the suitable degree of purity necessary for a drug.

Benzene↗

PubMed2001

Interaction between indomethacin and heavy metal ions in aqueous solution.

The interaction between indomethacin anions and heavy metal ions, such as cadmium, zinc and copper(II) ions, was studied in aqueous solution by polarographic techniques. Indomethacin anions form complexes with these heavy metal ions: the complex formed with cadmium ions is sparingly soluble, while more soluble and also stronger complexes are formed with zinc and copper(II). At high concentrations, where indomethacin anions undergo self-aggregation, these last compounds are solubilised. This property is briefly discussed and compared to that of bile salts. In the presence of calcium ions, indomethacin forms a poorly soluble salt and no evidence was detected for the formation of complex species.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Channeling agent and drug release from a central core matrix tablet.

A new oral dosage form for controlled and complete release of drug after a predetermined lag time is described. The system, designed to exploit the relatively constant small intestine transit time, consists of a drug-containing core coated with a polymeric matrix formed by a channeling agent (NaCl, mannitol, and Emdex) and an inert polymer (Eudragit RS100). The lag time was found to be dependent on type and particle size of the channeling substances used. Also, rheological properties of the binary mixtures (channeling substance--polymer) can affect the lag time periods. On the other hand, the release kinetics were found to be influenced significantly by excipient type and particle size. Results obtained from in vitro dissolution testing demonstrated that this device potentially could be used to deliver drugs orally for up to once-a-day dosing at controllable rates.

Administration, Oral↗

PubMed2000

Percolation thresholds in ultrasound compacted tablets.

Twenty matrix systems with different KCl content (as drug model, from 10 to 90% w/w) and Eudragit RS-PM (as inert excipient) were prepared using an ultrasound-assisted press and a traditional eccentric machine. The release behavior from both types of matrices was examined; the kinetic parameters for the release (intrinsic dissolution) and the technological properties of the final tablets (total porosity) were used to estimate the percolation threshold for the drug model and the excipient in both systems. For the systems compacted by ultrasound (US) the estimated value for the excipient percolation threshold ranges from 13.4 to 20.2% v/v (lower than that found for traditional tablets), that agrees with a continuum percolation model suggesting the presence of a continuum phase inside the tablet. This depends on a thermoplastic deformation of Eudragit RS-PM under ultrasound, that destroyed the particulate system of the excipient and transform it into a continuum medium. The percolation threshold for KCl ranged from 58.6 to 61.0% v/v for US and from 26.7 to 42.2% v/v for the traditional tablets. The higher value for ultrasound compacted tablets can be explained by the difficulty of KCl to outcome from a matrix containing insoluble phase that surrounds KCl crystals.

Excipients↗

PubMed2000

A rapid procedure to prepare cefotaxime.

A rapid procedure is reported for the synthesis of cefotaxime, by acylation of the 7-amino cephalosporanic acid with the 2-mercaptobenzothiazolyl thioester of (Z)-2-[2-aminothiazol-4-yl]-2-methoxyimino acetic acid (MAEM) that is a commercial reagent. The reaction was carried out at room temperature for 1 h, obtaining 95% yield. 2-Mercaptobenzothiazole was recovered as a side-product with a high purity and yield. The proposed method differentiates from those reported previously for a shorter time and very mild reaction condition, as well as for a ready for use reagent.

Cefotaxime↗

PubMed2000

Synthesis of (Z)-2-(2-formamido-4-thiazolyl)-2-(substituted alkoxyimino) acetic acids.

(Z)-2-(2-formamido-4-thiazolyl)-2-(substituted alkoxyimino) acetic acids were synthesized by a new method based on the following sequence of reactions: treatment of the tert-butyl acetoacetate with sodium nitrite, alkylation of the oxime formed with an appropriate alkyl halide, halogenation of methyl alpha-keto group and simultaneous cleavage of tert-butyl ester with sulfuryl chloride, protection of the obtained acid function with diphenyldiazomethane, formation of the 2-aminothiazole ring by the Hantzsch method with thiourea, formylation of the amino group and selective final cleavage of the diphenylmethyl ester by treatment with trifluoroacetic acid and anisol. The developed procedure allows the synthesis of (Z)-2-(2-formamido-4-thiazolyl)-2-(substituted alkoxyimino) acetic acids, with an ester function in the alkoxyimino group employing a simple method and obtaining higher yields in comparison with the habitually used classic method.

Acetates↗

PubMed1999

Formation of ion-pairs in aqueous solutions of diclofenac salts.

In this work we studied the ability of the diclofenac anion to form ion-pairs in aqueous solution in the presence of organic and inorganic cations: ion-pairs have a polarity and hydrophobicity more suitable to the partition than each ion considered separately and can be extracted by a lipid phase. The cations considered were those of the organic bases diethylamine, diethanolamine, pyrrolidine, N-(2-hydroxyethyl) pyrrolidine and N-(2-hydroxyethyl) piperidine; the inorganic cations studied were Li(+), Na(+), K(+), Rb(+), Cs(+). Related to each cation we determined the equilibrium constant (K(XD)) for the ion-pair formation with the diclofenac anion in aqueous solution and the water/n-octanol partition coefficient (P(XD)) for each type of ion-pair formed. Among the alkali metal cations, only Li(+) shows some interaction with the diclofenac anion, in agreement with its physiological behaviour of increasing clearance during the administration of diclofenac. The influence of the ionic radius and desolvation enthalpy of the alkali metal cations on the ion-pair formation and partition was briefly discussed. Organic cations promote the formation of ion-pairs with the diclofenac anion better than the inorganic ones, and improve the partition of the ion-pair according to their hydrophobicity. The values of the equilibrium parameters for the formation and partition of ion-pairs are not high enough to allow the direct detection of their presence in the aqueous solution. Their formation can be appreciated in the presence of a lipid phase that continuously extracts the ion-pair. Extraction constants (E(XD)=P(XD) times K(XD)) increase passing from inorga to organic cations. This study could help to clarify the mechanism of the percutaneous absorption of diclofenac in the form of a salt, a route where the formation of ion-pairs appears to play an important role.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Description and preliminary evaluation of a new ultrasonic atomizer for spray-congealing processes.

A new atomizer that operates with ultrasonic energy is described. This apparatus is intended to obtain microparticulate drug delivery systems through spray-congealing or spray-drying technologies. In this work, some experimental results are reported on model systems submitted to spray-congealing. The formulations under examination contained theophylline and fenbufen as model drugs and stearic acid, carnauba wax, Cutina HR(R) and Compritol 888 ATO(R) as low melting excipients. Non-aggregate and spherical-shaped microparticles were obtained with all the materials tested; moreover, they had smooth surface and good flowability. The particle sizes depend on the amount of drug present and in each case the maximum size value of the distribution frequency was found to be 375 mu. In vitro release of the drug depends on its solubility and on the excipient lipophilicity. The results suggest that the ultrasound-assisted atomizer could be proposed as a possible alternative to traditional atomizers used for spray-congealing in the pharmaceutical field.

Chemistry, Pharmaceutical↗

PubMed1999

Dehydration and rehydration of a hydrate diclofenac salt at room temperature.

The salt diclofenac/N-(2-hydroxyethyl) pyrrolidine crystallizes from water as a dihydrate, while it precipitates from organic solvents anhydrously: the two salts have different crystal structures. Dehydration of the dihydrate salt was carried out in a desiccator over silica gel at room temperature: the process occurs with the retention of the crystal structure. Slight changes observed in the diffractograms suggest, that soon after dehydration, a phase transition starts, slowly due to the low temperature of the process. The reaction was followed determining the loss of weight as a function of time and by thermal analysis, since the dihydrate and the dehydrate forms have different thermograms, but similar diffractograms. The reaction was complete after 24 h. The analysis of the experimental data suggests a kinetic process related to a one-dimensional diffusion of the crystallization water molecules outwards the solid particles. At room temperature, the dehydrate material rapidly back-absorbs the two molecules of crystallization water from the atmosphere moisture. The interaction with water of the different forms of the salt was discussed as a function of their solid structures as well as of the complex equilibria present in aqueous solution: these can explain previous apparently anomalous results.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Effect of the temperature on a hydrate diclofenac salt.

The salt Diclofenac/N-(2-hydroxyethyl) pyrrolidine when crystallizes from water forms a di-hydrate, which looses the crystallization water molecules on heating or in the presence of silica gel, undergoing a phase transition. The two processes were followed at room temperature, at 40 and 50 degrees C by thermal analysis and analyzing the dimensional parameters obtained by scanning electron microscopy as a function of the changes occurring in the solid state. The fractal dimension of the particle surface (DS) was determined for the di-hydrate, the anhydrate and the anhydrous forms: DS values are close together suggesting that the processes modify only slightly the external morphology of the particles. The reactive dimension (DR) to dissolution suggests that the salt after the thermal treatment has a dissolution behaviour identical to that observed for the salt obtained from organic solvents. The two processes de-hydration and phase transition can be carried out at relatively low temperature, suggesting an important pathway to obtain the anhydrous form starting from the di-hydrate one.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Effects of ultrasound-assisted compaction on Ketoprofen/Eudragit S100 mixtures.

Ketoprofen alone and in binary mixtures with Eudragit S100 was compacted by an ultrasound-assisted (US) tableting machine at an energy ranging from 50 to 400 J. The final material was analysed by TLC and HPLC: no decomposition product of the active agent was found. IR spectra and HSM revealed the absence of any interaction between the two components. Thermal analysis (DSC) evidenced that ketoprofen inside the mixtures was transformed into an amorphous state, documented by the decreasing of the DeltaHfus as the Eudragit/ketoprofen ratio increases and as US energy increases. While pure ketoprofen recovers its crystalline state quickly after the US treatment, the presence of Eudragit was found to slow down or possibly to prevent the regeneration of the crystallinity.

Acrylic Resins↗

PubMed1998

Study of the antioxidant effect of several selenium and sulphur compounds.

Four selenium derivatives (sodium selenate, sodium selenite, selenourea and selenomethionine) and the sulphur analogues (sodium sulfate, sodium sulfite, thiourea and methionine), together with urea, were examined by means of polarography to study their reactivity towards superoxide ion O2. In order that experimental results could be applied to physiological conditions and to control the electroreduction of oxygen, most reactions were carried out in model systems (in the presence and in the absence of triphenyl phosphine oxide and at increasing pH) which are briefly described and discussed. Sodium sulfite and thiourea react with molecular oxygen; selenourea originates an anodic wave, although under other pH conditions. Other compounds (selenate, selenite, seleno-methionine and methionine) display an interesting antioxidant capacity because they catalyse the disproportion of the superoxide ion, as documented by the increase in the limiting current. Methionine appears to be particularly efficient in this respect, since it retains its catalytic ability in a poorly protic environment. Experimental results support the view that exogenous compounds, administered for particular purposes, can display unanticipated, and sometimes positive, side effects.

Antioxidants↗

PubMed1998

[Prevalence of goiter and urine iodine in a school population in an area of the Bolognese Apennines].

We evaluated goiter prevalence and urinary iodine excretion (UIE) in schoolchildren living in three villages of the Appennines in the Bologna district-Castel d'Aiano (CA), Gaggio Montano (GM) and Pietracolora (PC). 175 age-matched schoolchildren living in the urban area of Bologna were considered as control group. In the control area the presence of goiter was documented in 11 out of 175 subjects (6.3%). In the mountain area the presence of goiter was documented in 42 out of 233 subjects (18%) (p < 0.0001 vs control area). In the urban control area the UIE was 159 micrograms/l (median; range 19-298). In the mountain area the UIE was 119 micrograms/l (median; range 10-286) (p < 0.001 vs control area). We observed the highest prevalence of goiter and UIE levels < 100 micrograms/l only in the village of PC, which is still characterized by geographical isolation and rural economy.

Biomarkers↗

PubMed1998

Myocardial perfusion, glucose utilization and oxidative metabolism in a patient with left bundle branch block, prior myocardial infarction and diabetes.

A diabetic patient affected by insulin-dependent diabetes, significant stenosis of left anterior descending (LAD) coronary, thrombolyzed myocardial infarction and complete left bundle branch block (LBBB) was examined by PET. Myocardial perfusion, glucose utilization and oxidative metabolism were evaluated by 13N-ammonia, 18F-fluorodeoxyglucose (FDG) and 11C-acetate, respectively. Despite severe damage in 18F-FDG uptake in the septum, with a septum-to-lateral ratio (S/L R) equal to 0.38, the oxidative metabolism in this area, evaluated quantitatively by dynamic acquisition, was relatively preserved (S/L R = 0.82), with a distribution similar to perfusion (S/L R = 0.87). These data reveal selective damage in glucose utilization in the septum in LBBB, unrelated to perfusion reduction and with preserved oxidative metabolism. Moreover, our experience could suggest an overestimation of the necrotic area by 18F-FDG in LBBB patients.

Acetic Acid↗

PubMed1997

Interaction of iron(II) with bile salts.

Iron(II) ions react with small aggregates of cholate, glycocholate, chenodeoxycholate, and deoxycholate to form soluble and colloidal compounds. Taurocholate under conditions used does not react with the Fe2+ ion. Small aggregates of dihydroxy bile salts (predominating in the premicellar region, at concentrations of the bile salt above 1 mmol dm-3) have a larger affinity for Fe2+ compared to those formed from cholate anions. In their interactions with small aggregates of cholate anions, the Fe2+ ion shows an affinity comparable to that of Cu2+ and Cd2+ and somewhat larger than that of Zn2+. Small aggregates of cholate show a higher ability to mask Fe2+ than those of taurocholate and glycocholate. Interaction of glycocholic acid anions with Fe2+ ions is sufficient to prevent iron(II) precipitation.

Anions↗

PubMed1997

Fractal analysis of beta-cyclodextrin-indomethacin particles compacted by ultrasound.

An association between indomethacin and beta-cyclodextrin (beta-CD) was obtained by compacting a 1:2 molar physical mixture by ultrasound. The product prepared by this technique was compared with the initial physical mixture and with materials having the same composition but prepared by a simple compaction and kneading process. The samples examined by scanning electron microscopy revealed morphological differences related to the methods of preparation. In particular the material obtained by ultrasound had a smooth surface and on milling produced particles of uniform size; moreover EDAX analysis (energy dispersion analysis by X-rays) also revealed a homogeneous distribution of the two components in each particle examined. Surface fractal dimension of the surface of these particles is very low, suggesting the presence of a regular and smooth surface whereas the sample obtained by kneading had a higher value. The reactive dimension related to dissolution was much higher than the corresponding surface dimension in all cases and had comparable values for all samples regardless of the techniques used. This behavior was attributed to the hydrophilicity of beta-CD, which levels the differences during dissolution and which could be originated by surface imperfections. Experimental results suggested that the material obtained by ultrasound had a dissolution rate comparable to that measured with the kneaded material. The use of ultrasound, however, can both reduce the production time and improve the homogeneity of the association between indomethacin and beta-CD.

Cyclodextrins↗

PubMed1996

Interaction between trace elements: selenium and cadmium ions.

The interaction between several inorganic and organic selenium-containing compounds (selenite, selenate, selenourea and selenomethionine) and Cd2+ ions was studied by polarography. The changes in polarographic currents and half-wave potentials of the metal ions as a function of the Se-derivative concentration were followed. Experimental results suggest a different behaviour depending on the oxidation state of selenium. Any interaction between selenate and Cd2+ ions can be excluded. In the case of selenite, the presence of complexes in the solution was demonstrated. The shift in the Cd2+ reduction half-wave potential when a relatively high concentration of selenourea is present indicates formation of complexes, while the decrease in limiting current reflects the limited solubility of the complex itself. Results concerning selenomethionine suggest a very weak interaction with Cd2+ ions. These preliminary results are discussed in comparison with previous findings in cellular systems and may prove helpful in understanding cadmium ion toxicity and the in vivo altered distribution of various metal ions following the administration of selenium compounds.

Cadmium↗

PubMed1996

Fractal analysis of sodium cholate particles.

A fractal analysis was carried out on the powder particles of two samples of sodium cholate. A commercial sample had very irregular particles agglomerated, and accordingly the fractal dimension of the surface was 2.98, suggesting a noteworthy roughness of the particle surface; scanning electron microscopy showed that this was due to irregularities caused by a disordered agglomeration of very small particles, resulting in larger particles showing polygonal and smooth but limited facets. A second sample was obtained by recrystallization from ethanol of the commercial sodium cholate and contained large and regular particles, with very smooth surfaces. The fractal dimension therefore was accordingly low. Despite these differences, the two samples had similar, high reactive dimension values to dissolution (2.96 and 2.76, respectively), suggesting that the surfactant behavior of sodium cholate is an important parameter in driving the dissolution of the solid particles and leveling the surface defects.

Cholic Acid↗