Biomedical subjects

A C Calpena

Publications and source records attributed to A C Calpena.

9 recordsLinked to original sources

PubMed2005

Rapid human skin permeation and topical anaesthetic activity of a new amethocaine microemulsion.

We developed a fast-acting, topical, 4% (w/w) amethocaine microemulsion and tested its in vitro permeation in isolated human skin. Comparison with a commercial amethocaine gel (Ametop((R)) ) was performed using Franz diffusion cells. Permeability coefficient (k(p)), flux (J) and percentage permeation after 10 h of microemulsion application were, in all cases, 1.5 times higher than those of the gel. The values obtained for the P(1) parameter [1], 1.06.10(-2) cm (microemulsion) and 0.724.10(-2) cm (gel) indicate that the microemulsion excipients favour amethocaine deposition in the skin, increasing the permeability coefficient, amount of drug retained in the skin, and the flux achieved. Analgesic activity was also examined in rats made hyperalgesic or allodynic after carrageenan-induced inflammation. The rats were distributed into four groups (n = 5-9 per group), each group receiving topically either amethocaine microemulsion, amethocaine gel (Ametop), amethocaine subcutaneous infiltration or nothing (controls). In edematous paws, anti-hyperalgesic activity appeared at 4.2 and 13.8 min after application of amethocaine microemulsion and gel, respectively. These effects are lower than after 0.5% w/w amethocaine infiltration. Amethocaine microemulsion was the only topical formulation with an anti-allodynic effect, although this effect was less than with amethocaine infiltration. These results suggest that microemulsion could be a valuable formula for improving amethocaine permeation and thus bringing rapid pain relief.

Administration, Topical↗

PubMed2004

Comparative study of morphine diffusion from sustained release polymeric suspensions.

In recent years, great efforts have been devoted to the design of drug delivery systems. Many polymeric excipients have been studied in order to make drug release fit the desired profiles. The aim of this work was to design a morphine oral suspension, as sustained release pharmaceutical formulations. To this end, two different ethylcellulose suspensions were prepared: one with the drug incorporated during synthesis (suspension A) so that the drug was inside the polymeric microparticles. In the second group of suspensions the drug was incorporated after synthesis (suspension B), thus resulting in the drug being adsorbed on the surface. The analytical technique used, spectrophotometry, showed that suspensions A were able to spontaneously encapsulate approximately 92% of the drug, whereas suspensions B adsorbed only 15% dose on the particle surface. Moreover, the diffusion results obtained with Franz-cells showed that suspensions A offered the possibility of easy control of the release rate of the active substance. This system transfers morphine hydrocloride during 24 h in accordance with a Weibull kinetic model. This dosage form presents the clinical advantage of less frequent dosing, with increased quality of life for patients. This report documents the suitability of our ethylcellulose polymeric suspension for encapsulated morphine with a controlled release rate.

Analgesics, Opioid↗

PubMed1999

Influence of the formulation on the in vitro transdermal penetration of sodium diclofenac. Evaluation of the topical and systemic anti-inflammatory activity in the rat.

A study on the transdermal permeation through human skin was performed with a series of 6 semisolid formulations (A-F) containing 1% sodium diclofenac (CAS 15307-79-6) (w/w). A commercially available drug preparation was tested as a reference. Based on permeation characteristics, a study on the topical and systemic anti-inflammatory activities of three formulations (A, F and the reference formulation) was conducted using the model of erythema induced by UV radiation in hairless rats. This is expected, together with the index of topical anti-inflammatory activity to allow the selection of the most suitable formulation for dermal application. The following representative parameters were measured in the permeation study: amount of diclofenac permeated at 24 h, flow, lag time and amount of drug retained in skin at 24 h. Of the formulations tested, diclofenac formulated in the reference formulation showed the highest values of amount of diclofenac permeated at 24 h, amount of drug retained in skin at 24 and flow. As regards the skin inflammation test, no significant differences (p < 0.05) are seen between the topical and systemic anti-inflammatory activities of the three formulations tested. However, in absolute value, formulation F shows a lower systemic activity, which would prevent potential side effects of diclofenac. Since the topical anti-inflammatory index obtained for this formulation was > 1, it is concluded that a good therapeutic performance could be obtained in the treatment of local inflammation with diclofenac by using formulation F.

Administration, Cutaneous↗

PubMed1997

Structure-absorption relationships of a series of 6-fluoroquinolones.

The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally.

Animals↗

PubMed1994

A comparative in vitro study of transdermal absorption of antiemetics.

Transdermal absorption of a series of antiemetics (alizapride, bromopride, clebopride, domperidone, metoclopramide, metopimazine, and scopolamine) was studied in vitro with the skin of hairless rats as the membrane. The aim of the study was to determine the permeation parameters [transdermal permeability rate constant (Kp), lag time, and flux] as a measure of the intrinsic permeability of these drugs across the skin, with a view to predicting their potential therapeutic formulation in Transdermal Therapeutic Systems. A linear correlation was established between the log Kp values corresponding to the antiemetics studied and their melting point (r = 0.8120, p < 0.05). The logarithm of Kp for the antiemetics studied can be predicted from the logarithm of the intrinsic partition coefficient (n-octanol-water) by a parabolic function (r = 0.9284, p < 0.01). Bromopride showed the shortest lag time (19.73 h), whereas clebopride was the most suitable drug as a candidate for formulation in transdermal delivery systems.

Administration, Cutaneous↗

PubMed1993

Influence of the chromatographic capacity factor (log k') as an index of lipophilicity in the antibacterial activity of a series of 6-fluoroquinolones. Relationship between physico-chemical and structural properties and their hydrophobicity.

The aim of this study was to establish the influence of lipophilicity on the antibacterial activity (log 1/MIC50) of 22 fluoroquinolones and to assess the influence of their electronic, steric and topological properties on their hydrophobicity. The lipophilicity of the compounds, expressed as the chromatographic capacity factor (log k'), was determined by ion-pair reversed-phase HPLC. On the basis of the mathematical models developed, an attempt was made to confirm the mechanism of interaction of the quinolones with DNA-gyrase proposed previously.

Anti-Infective Agents↗

PubMed1992

Gastric, intestinal and colonic absorption of a series of beta-blockers in the rat.

Gastric, intestinal and colonic absorption rates of a series of eleven beta-blockers (alprenolol hydrochloride, atenolol, bunolol hydrochloride, penbutolol sulphate, pronethalol hydrochloride, metoprolol, oxprenolol, bevantolol, bufuralol, propranolol hydrochloride and timolol maleate) were estimated using Doluisio's method. The gastric absorption rate was very low and the absorption rate constant could not be assessed accurately in all cases. In the small intestine, the absorption rate constants, Ka, at pH 6.2 ranged between 0.38 h-1 for atenolol and 4.28 h-1 for penbutolol. In the colon, the rate of drug absorption at pH 7.5 ranged between 0.12 h-1 for atenolol and 2.15 h-1 for penbutolol. In most cases, colonic absorption rate constants were of the same order as those obtained in the small intestine, demonstrating the good penetrability through colonic membrane of the series studied. The relationship between absorption rate constants found in the small intestine and colon and the partition constant ([1/Rf]-1), was studied for this non-homologous series of beta-blocker drugs. In both cases, the functional hyperbolic absorption model proposed by Wagner and Sedman [1973] was the most representative.

Absorption↗

PubMed1991

Skin density in the hairless rat. Evidence of regional differences.

Skin densities of different regional sites have been determined in the hairless rat. The following regional sites have been considered: abdominal, dorsal, foreleg, rearleg, pectoral, neck (ventral and dorsal) and scrotal. Skin density values were determined by means of an hydrostatic balance. The dorsal regional site and the neck dorsal show the highest density values (1.076 and 1.070 respectively). The scrotal regional site shows the lowest density value 1.041. The abdominal density mean value (1.054) was not different from the foreleg, rearleg, pectoral and neck (ventral) regional sites. The knowledge of these density values will be useful to estimate skin/vehicle partition coefficients.

Animals↗

PubMed1991

Intestinal absorption of a series of 6-fluoquinolone derivatives: a comparative study.

The intestinal absorption rate constants of the five 6-fluoquinolones (norfloxacin, ciprofloxacin, pefloxacin, CNV 8802 and CNV 8804), have been estimated in the rat (n = 5) by means of an "in situ" intestinal perfusion method. Remaining 6-fluoquinol one concentrations in the perfusion liquid at fixed time (15, 30, 45, 60, 75, 90 and 120 minutes) were determined using a HPLC procedure with UV detection. Absorptions rate constants were estimated according to first order kinetics. A simple non-linear correlation between Ka and log K' on the one hand and a multiple linear correlation between Ka and the structural theoretical parameters: molar volume, dipolar moment and the charge associated to nitrogen 18 on the other, were performed. Only a correlation between Ka values as dependent variable versus dipolar moment and molecular volume values has been obtained, but this correlation is not statistically significant (p = 0.1808) and not accurate enough to have predictive value.

4-Quinolones↗