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Biomedical subjects

G Frutos

Publications and source records attributed to G Frutos.

16 recordsLinked to original sources
PubMed2004

Nonlinear mixed-effects model for the dissolution assays of drugs.

Sustained or controlled release delivery systems can achieve predictable and reproducible drug release rates. With the aim of optimizing the bioavailability of conventional drugs with minimum side effects, new drug delivery systems continue to attract much attention. This research has been addressed to investigate in vitro metoclopramide release behavior from inert polymeric matrix tablets. Model-dependent and model-independent approaches are commonly used to investigate the release process and a fitted model results for each experimental condition. The aim of this work was to study the release characterization of the whole batch, therefore, we have developed a population model, taking into account the differences between tablets, experimental conditions, heterogeneity, and autocorrelation of residuals. The study of dissolution profiles was carried out using a mixed-effect model, which has provided a satisfactory tool for this kind of data.

Models, Chemical↗
PubMed2003

Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose.

Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult.

Anti-Bacterial Agents↗
PubMed2002

Release of gentamicin sulphate from a modified commercial bone cement. Effect of (2-hydroxyethyl methacrylate) comonomer and poly(N-vinyl-2-pyrrolidone) additive on release mechanism and kinetics.

The influence of the (2-hydroxyethyl methacrylate) (HEMA) monomer addition as a comonomer to the cement liquid component and of a polymer, poly(N-vinyl-2-pyrrolidone) (PVP) to the solid component of a standard CMW-1 bone cement on gentamicin sulphate (GS) on its drug release properties have been studied. The addition of HEMA modifies the habit of the delivery curves. The incorporation of PVP into the cement matrix, apparently, did not very much modify the shape of the HEMA modified cement release curves, but led to a remarkable increase of the maximum amount of GS released. This effect was proportional to the PVP concentration incorporated. From the matrix composition and SEM data, a model based on the morphology of the matrix has been proposed. The cumulative amount of GS released by each slab Mt is most adequately fitted and represented by the equation Mt = c + at 1/2 + b[1 - exp(-nt)], which corroborates that the release occurs according to the model proposed. by means of three discrete mechanisms, namely: (i) a short-term initial elution due to the imperfections in the poly(methyl methacrylate) covering of the most external GS beads, burst effect by the buffer solution; (ii) followed by a fracture by stress cracking in an active media of the coated GS beads located on the external surface of the matrix where water molecules enter to dissolve GS molecules releasing them into the buffer solution by a diffusion-controlled process; and (iii) a third process in which the buffer solution penetrates into the internal voids and cracks creating a series of channels in a labyrinthic structure, which may facilitate the access of water molecules to the plastic-coated GS beads within the bulk matrix. This third process is enhanced by the incorporation of PVP beads as dissolved molecules within the matrix. This water-soluble additive is leachable, generating a highly porous structure in the cement. This HEMA and PVP modified cement may be used as a drug delivery system to modulate the GS release rate.

Anti-Bacterial Agents↗
PubMed2001

Gentamicin bone cements: characterisation and release (in vitro and in vivo assays).

Due to the extended use of acrylic bone cements, its necessary to develop improved formulations in order to resolve their many drawbacks. The present work was conducted to make a physical-chemical characterisation of this kind of acrylic cement in order to introduce future changes in the formulations to: (1) improve or at least maintain their mechanical properties; (2) diminish their toxicity, and (3) control the drug release (rate and amount). From the dissolution method we can conclude that the preparation method (with or without pressure) of specimens is not responsible for the erratic release. The cumulative amount of gentamicin released was fitted to a semi-empirical equation to explain the possible release mechanism. The powder size, shape and distribution that could affect several properties of bone cement were studied with the aid of different techniques such as SEM, laser diffraction spectroscopy, and powder X-ray diffraction. From SEM micrographs, it was possible to observe that the surfaces of the specimens were very irregular with numerous small craters that may serve as conduits for eluting the antibiotic. An 'in vitro' drug diffusion model is proposed to elucidate the drug release mechanism. Finally an 'in vivo' study was performed to evaluate the antibiotic release to the neighbouring bone sites.

Acrylic Resins↗
PubMed2001

In vitro release of metoclopramide from hydrophobic matrix tablets. influence of hydrodynamic conditions on kinetic release parameters.

There has been growing interest in the subject of drug delivery and the design and evaluation of controlled-release systems. The simplest way to control the release of an active agent is to disperse it in an inert polymeric matrix. Controlled-release systems are of interest because they are technologically simple, relatively cheap, and practically unaffected by physiological changes. In this study, a new matrix system was formed by an active principle, metoclopramide hydrochloride, scattered into a biocompatible hydrophobic polymerical mesh, polyamide 12, to achieve sustained and controlled delivery of metoclopramide hydrochloride. This research was conducted to investigate the in vitro drug release behavior from these new inert polymeric matrix tablets. The drug release process was investigated both experimentally and by means of mathematical models. Different models were applied for the evaluation of drug release data. On the basis of our results, a biexponential equation was proposed, Q=Qfast(1)(1 - e(-Kfast t)) + Qslow(2)(1 - e(-Kslow t)), in an attempt to explain the mechanism responsible for the release process. Additionally, the influence of the experimental conditions of the dissolution devices, such as rate of flow and pH of dissolution medium, on the parameters that characterize the release mechanism was studied, and it was found that the main factor was the hydrodynamic condition of rate of flow.

Algorithms↗
PubMed2000

Validation and in vitro characterization of antibiotic-loaded bone cement release.

Antibiotic-loaded polymeric bone cement is used in orthopedic surgery to deliver local high concentrations of antibiotics to the tissues. The precise mechanism by which antibiotic is released from the polymeric matrix is still not very well known. This research was conducted to investigate the in vitro drug release behavior of antibiotic from acrylic bone cement. A spectrophotometric method for the quantitative analysis of gentamicin sulfate using o-phtaldialdehyde as a derivatizing reagent was thoroughly validated, in order to assure a minimum quality level of the measures. The method proved to be quick, reliable, less expensive than methods such as polarization fluorescence immunoassay and others, and therefore more convenient for the routine analysis of the numerous samples generated during in vitro liberation assays. The release of gentamicin from commercial CMW1 acrylic bone cement samples was investigated following proposed in vitro release experiments.

Algorithms↗
PubMed2000

A validated quantitative colorimetric assay for gentamicin.

A colorimetric procedure was developed for the quantification of gentamicin. The method was based on the ninhydrin reaction with primary and secondary amines present in the gentamicin. This reaction produces a purple colour. The effects of several factors including pH, ninhydrin concentration and reaction time were investigated to optimize the assay method. Using the assay protocol, the absorption of the gentamicin-ninhydrin mixtures at 400 nm had a linear relationship with the gentamicin concentration ranging from 30 to 120 microg/ml. The colorimetric gentamicin assay reported herein is of great practical value because it is reproducible, sensitive, simple and extremely inexpensive.

Colorimetry↗
PubMed2000

Enhancement of the mydriatic response to tropicamide by bioadhesive polymers.

The aim of this work was to evaluate how the addition of mucoadhesive polymers to aqueous solutions affects the ocular response of tropicamide (0.2%; w/v). The polymer solutions tested were carboxymethylcellulose sodium salt (CMC-Na; 1%; w/v), hyaluronic acid sodium salt (HA-Na; 0.1%; w/v) and polyacrylic acid (PAA; 0.2%; w/v). Polymeric solutions were compared to a nonviscous formulation (AS). In vitro mucoadhesion measurements were expressed as a percentage of the adhesion force mucin-mucin, considering this one as 100% mucoadhesion. The values ofmucoadhesion obtained were 172%, 127%, 103% and 87.6% for formulations with CMC, PAA, HA and AS, respectively. The mydriatic response of tropicamide was determined in adult male New Zealand rabbits, weighing 1.7-2 Kg, by pupil diameter measurements at different times after instillation. The area under the mydriatic response-time curve (AUC 0-6 hr) was interpreted as an indication of the bioavailability of tropicamide in each vehicle. The AUC 0-6 hr was related to the in vitro mucoadhesion for each formulation. Tropicamide solutions with CMC-Na and PAA resulted in mucoadhesion and AUC 0-6 hr values approximately 1.9 and 1.4 times higher than AS. Although the solution with HA-Na was less mucoadhesive than PAA, the hyaluronic acid solution resulted in a higher AUC mydriasis/time value. Formulations with HA-Na and PAA presented values of surface tension close to that observed in the lacrimal fluid, with the Imax (maximum pupil diameter) being higher than for CMC-Na and AS. Greater than 90% of the mydriatic effect disappeared 4.5 hr after instillation for PAA and AS. Nevertheless, the mydriatic effect remained up to 5.5 hr for HA-Na and CMC-Na. HA-Na solution enhanced the bioavailability oftropicamide, presenting a value of mucoadhesion similar to the reference mucin-mucin.

Acrylic Resins↗
PubMed1993

Characterization of 5-fluorouracil loaded liposomes prepared by reverse-phase evaporation or freezing-thawing extrusion methods: study of drug release.

Entrapment of the anti-tumoral drug 5-fluorouracil (5-FU) in unilamellar liposomes prepared by freeze-thawing extrusion technique (FATVET) and the reverse-phase evaporation method (REV) from natural (bovine brain) sphingomyelin (SM) and synthetic distearoylphosphatidylcholine (DSPC) phospholipids was studied. Reverse-phase evaporation vesicles obtained from DSPC sized through polycarbonate membranes of 0.2 micron pore size were found to entrap roughly double amounts of drug than did extruded liposomes (0.1 micron pore size); however, s-REV in these preparations were more heterogenous in vesicle size than FATVET. The rate of in vitro drug release from the liposomes was found to be dependent of the bilayer composition and the method used to prepare the vesicles. The permeability coefficient P obtained was approx. 10(-11) m/s. The results suggest that 5-FU release is kinetically controlled by an interfacial process seemingly dependent on the surface activity of the drug. Also, the physical state of the bilayer determines the retention capacity of the vesicles. Thus, liposomes consisting of distearoylphosphatidylcholine whose acyl chains were in a gel state at the working temperature (37 degrees C) retained 70% of encapsulated 5-FU after 1 h, whereas liposomes composed of natural bovine brain sphingomyelin retained only 15% over the same period.

Animals↗
PubMed1992

Fluorescence quenching of human serum albumin by xanthines.

A study of the fluorescence quenching of human serum albumin (HSA) by caffeine, theophylline and theobromine, based on temperature dependence, has shown that it is predominantly static. This quenching mechanism is due to the formation of a xanthine-HSA non-fluorescent complex. The Stern-Volmer equation let us determine the association constants. It seems that the quenching of the protein fluorescence depends on the number and position of the methyl groups. The temperature dependence of the association constant is used to estimate the values of the thermodynamic parameters involved in the interaction of the drugs with HSA. All three binding processes are exothermic and probably hydrophobic, and hydrogen bonds play a significant role in the stabilization of such complexes. The enthalpy and entropy changes observed appear to compensate each other to produce a relatively small Gibbs free energy.

Caffeine↗
PubMed1991

Chlorpheniramine binding to human serum albumin by fluorescence quenching measurements.

The binding of chlorpheniramine to human serum albumin has been studied by fluorescence quenching, as a function of temperature; the experimental data could only be fitted to the Stern-Volmer modified equation. A statistical analysis of the results was performed in order to determine the significance of the constants calculated by this equation, as well as their thermodynamic parameters. The chlorpheniramine binding to human serum albumin accounts for almost half of the binding of this antihistaminic agent to human plasma proteins.

Chlorpheniramine↗
PubMed1985

[In vitro combination of mercaptopurine and human serum albumin].

Through the use of the fluorescence absorbance technique, the parameters that define the association between the antineoplastic drug mercaptopurine and human serum albumin were determined for a concentration range for the ligand between 6 X 10(-5) and 10(-7) moles/L, keeping the concentration of the macromolecule fixed at 0.5 X 10(-6) moles/l. Given the structure of the macromolecule under study and the experimental conditions used, we established an association model with two different kinds of binding sites.

Drug Interactions↗