PubMed Health⌕ Search

Biomedical subjects

A M Rabasco

Publications and source records attributed to A M Rabasco.

At least 19 recordsLinked to original sources
PubMed2005

Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes.

The main objective of the present work was to compare the dermal delivery of minoxidil (Mx), a lipophilic drug from ethosomes versus classic liposomes, containing different cholesterol (CHOL) concentrations. All the systems were characterized for shape, lamellarity, particle size and entrapment efficiency percentage (EE), by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser diffraction and ultracentrifugation or dialysis methods, respectively. Multilamellar vesicles (MLVs) were obtained and one to six lamellae were visualized by CLSM. The presence of ethanol in the formulations affects the particle size in terms of reducing this parameter. In addition, it was possible to appreciate the influence of CHOL on the vesicle size, because it was increased, as CHOL concentration was higher. When the EE was determined by two different methods (ultracentrifugation and dialysis methods), a clear losing of entrapped drug by the ultracentrifugation method was observed, because the strong energy transmitted to the samples disrupted vesicles. Vesicles were non-occlusively applied on rat skin and the permeation pattern of the different systems, depth into the skin and the main permeation pathway were studied by using beta-carotene as a fluorescent probe. CLSM studies showed that ethosomal systems were much more efficient at delivering the fluorescent substance into the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solutions.

Androstanes↗
PubMed2004

Characterization of ibuproxam binary and ternary dispersions with hydrophilic carriers.

This work investigates the possibility of increasing the dissolution properties of ibuproxam (a poorly water-soluble anti-inflammatory drug) using hydrophilic carriers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), or urea, alone or in combination. Phase-solubility studies showed that the carrier solubilizing power was in the order PEG>PVP>urea and evidenced a synergistic effect in drug solubility improvement when using carrier combinations. Binary and ternary systems, at 20/80 or 20/40/40 (w/w) drug/carrier(s) ratios, prepared by coevaporation of their ethanolic solutions or by cogrinding physical mixtures in a high-energy vibrational micromill, were characterized by differential scanning calorimetry (DSC), hot stage microscopy (HSM), and scanning electron microscopy (SEM) analyses. The results of dissolution tests (USP paddle method), in terms of Dissolution Efficiency, indicated that ternary systems were up to 35% more effective than the corresponding binary preparations and coevaporated products were up to 45% more efficacious than the corresponding coground ones. The IBUX-PEG-PVP coevaporated was the best product, allowing a more than three-times increase in Dissolution Efficiency with respect to drug alone; moreover, t50% (> 60 min for pure ibuproxam) was < 10 min, and 90% dissolution was achieved after 30 min, whereas only 40% was obtained after 60 min for pure drug. The best performance of this system was attributed to a joined effect of the strong amorphizing power of PVP (as demonstrated by solid state analyses) with the high solubilizing efficacy of PEG (as emerged from phase-solubility studies). The drug dissolution rate from solid dispersions remained practically unchanged after one-year storage at room temperature in closed containers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Study of glimepiride-b-cyclodextrin complex.

The interaction of glimepiride with b-cyclodextrin (b-CD) has been studied by several analytical techniques, including 1H NMR, infrared spectroscopy (FTIR), powder x-ray diffractometry (XRD), thermal analysis (DSC) and scanning electron microscopy (SEM). The existence of an inclusion complex was proved in solution by phase solubility techniques and 1H NMR, and in the solid state by DSC, FTIR and XRD, being isolated by sealed heating and freeze drying procedures.

Calorimetry, Differential Scanning↗
PubMed2002

Alginate/chitosan particulate systems for sodium diclofenac release.

Alginate/chitosan particles were prepared by ionic gelation (Ca2+ and Al3+) for the sodium diclofenac release. The systems were characterized by electron microscopy and differential scanning calorimetry. The ability to release the active substance was examined as a function of some technological parameters and pH of dissolution medium. The release of sodium diclofenac is prevented at acidic pH, while is complete in a few minutes when pH is raised up to 6.4 and 7.2. The alginate/chitosan ratio and the nature of the gelifying cation allow a control of the release rate of the drug. The release mechanism was briefly discussed.

Alginates↗
PubMed2002

Eudragit RS-PM and Ethocel 100 Premium: influence over the behavior of didanosine inert matrix system.

Inert matrices of didanosine (ddI) were elaborated as controlled release dosage forms, using two different types of polymers: Eudragit RS-PM, an anionic acrylic acid copolymer, and Ethocel 100 Premium, an ethylcellulose. A preformulation study of the drug was designed to address the following points: (a) the development of two alternative methods (high performance liquid chromatography (HPLC) and UV spectrophotometry) for the analysis and quantifying of ddI; (b) the determination of the aqueous solubility of ddI; and (c) the characterization of ddI from the following points of view: morphological (scanning electronic microscopy (SEM)) and thermal (differential scanning calorimetry (DSC)). Furthermore, some of these techniques were used for the characterization of those components which will be included in the oral controlled release system to be developed. The in vitro release of ddI matrices was studied at pH 7.4, because of the instability of ddI at pH values lower than 3 units. A significant reduction in the release rate of drug from both ddI controlled release systems was found. Furthermore, Ethocel 100 Premium showed a minor efficiency in the dissolution process, with a reduction of more than double in the final dissolution efficiency (DE) value. This parameter and the fit factors (f1 and f2) have been compared for the characterization of dissolution profiles.

Acrylic Resins↗
PubMed2001

Estimation of the percolation thresholds in dextromethorphan hydrobromide matrices.

Percolation theory is a multidisciplinary theory that studies chaotic systems. It has been applied in the pharmaceutical field since 1987. Knowledge of the percolation threshold -- one of the most important concepts in percolation theory -- results in a clear improvement of the solid dosage form design. The percolation threshold is the concentration showing the maximum probability to obtain, for the first time, a percolating cluster of a substance. In this work, the percolation thresholds of dextromethorphan.HBr/Eudragit RS-PM inert matrices were estimated. The drug percolation threshold was estimated as 0.3691+/-0.0541 (P=0.05) of the total porosity (ranging between 23 and 36% w/w of drug). The SEM micrographs of the matrices are consistent with the estimated percolation range. In agreement with previous reports, different percolation thresholds were found for the matrix forming excipient Eudragit RS-PM. The site percolation threshold (based on the release properties) ranged between 10 and 20% v/v of the excipient, the site-bond percolation threshold (estimated from the mechanical properties) between 29.5 and 34% v/v of the excipient and the swelling percolation threshold between 34.3 and 46.9% v/v of the excipient. These percolation ranges are in agreement with those found previously for Eudragit RS-PM matrices containing naltrexone.HCl and morphine.HCl.

Acrylic Resins↗
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↗
PubMed1999

Design of controlled release inert matrices of naltrexone hydrochloride based on percolation concepts.

The percolation theory is a statistical theory able to study chaotic or disordered systems that has been applied in the pharmaceutical field since 1987. Through the application of this theory, the design of controlled release inert matrices has been improved. The aim of the present paper is to estimate the percolation thresholds, the most important concept of the percolation theory, which characterise the release behaviour of controlled release inert matrices of naltrexone hydrochloride. Matrix tablets were prepared using naltrexone hydrochloride as a potent narcotic antagonist and Eudragit(R) RS-PM as matrix forming material in different ratios, keeping constant the drug and excipient particle sizes. In vitro release assays were carried out exposing only one side of the tablets to the dissolution medium. The drug percolation threshold was estimated using different methods. The method of Leuenberger and Bonny gives 31.11+/-7.95% v/v as the critical porosity, which corresponds to a percolation range from 12 to 20% (w/w) of drug content. The release profiles and the release kinetics are in agreement with this result. A change in the exponent k (from 0.29 to 0.57) has been found in this region. Using scanning electron microscopy, the percolation threshold has been observed in a higher concentration range (20-35% w/w). This fact can be attributed to the low accuracy of the visual methods, mainly due to the extrapolation from 2D to 3D systems. If a percolating cluster is observed in two dimensions, the percolation threshold of the 3D system will be already clearly exceeded. The excipient percolation threshold is estimated between 25.4 and 31.1% (v/v) based on the release profiles and the analysis of the release kinetics.

Acrylic Resins↗
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

Evaluation of Eudragit RS-PO and Ethocel 100 matrices for the controlled release of lobenzarit disodium.

Lobenzarit disodium is a drug for the treatment of rheumatoid arthritis. In this work, inert matrix tablets of lobenzarit disodium were prepared by direct compression using Ethocel 100 and Eudragit RS-PO as polymeric materials in different ratios. The obtained powder mixtures and tablets were evaluated from the rheological and technological points of view. The dissolution test was performed to evaluate the in vitro release kinetic of the matrices. The obtained dissolution profiles demonstrated that the matrices containing Eudragit RS-PO showed a slower release rate and therefore were more suitable for controlling the release of drug. The fit to the Higuchi model indicates that the drug release mechanism from these matrices was controlled by the diffusion step.

Acrylic Resins↗
PubMed1999

Effects of the host cavity size and the preparation method on the physicochemical properties of ibuproxam-cyclodextrin systems.

The effect of cyclodextrin (Cd) complexation on ibuproxam (IBUX) dissolution properties was studied by evaluating both the influence of Cd cavity size and the preparation method used for obtaining solid inclusion complexes. Binary systems of IBUX with natural Cds, prepared using different techniques (kneading, sealed-heating, spray-drying), were studied by differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and their dissolution behavior was evaluated according to the dispersed amount method. The nature and the dissolution performance of the end product appeared to be related to both steric factors of host molecule and preparation method of the solid system. The alpha Cd cavity size was less suitable for accommodating the IBUX molecule, whereas spray-drying and sealed-heating methods led to a true inclusion complex of IBUX in the beta Cd and gamma Cd cavity. In contrast, the kneading method did not lead in any case to a real inclusion complex. Spray-dried systems with beta Cd and gamma Cd were the most effective in achieving the enhancement of the IBUX dissolution rate.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

The role of the drug/excipient particle size ratio in the percolation model for tablets.

PURPOSE: In previous papers, a linear relationship between drug particle size and drug percolation threshold was found in inert matrix tablets. The main objectives of the present work are: to study the influence of the excipient particle size on the drug percolation threshold and to investigate if the change in the drug percolation threshold is due either to the absolute or to the relative drug particle size. METHODS: Matrix tablets have been prepared using KCl (7 different particle size fractions) as a drug model and Eudragit RS-PM (4 granulommetric fractions) as matrix forming material. In vitro release assays were carried out on the 66 lots of tablets. The drug percolation thresholds were estimated following the method of Bonny and Leuenberger. RESULTS: The particle size of the excipient has shown an opposite effect to the drug size on the drug percolation threshold. Nevertheless, the influence of drug and excipient sizes on the drug percolation threshold are of the same magnitude. CONCLUSIONS: The drug percolation threshold depends linearly on the relative drug particle size. This finding is in agreement with percolation theory and can facilitate the use of the percolation threshold as a preformulation parameter to improve the pharmaceutical dosage forms design.

Chemistry, Pharmaceutical↗
PubMed1997

Nuclear magnetic resonance investigations of the inclusion complexation of gliclazide with beta-cyclodextrin.

The formation of the gliclazide-beta-cyclodextrin (GL-beta-CD) inclusion compound has been studied in the liquid state by phase solubility techniques and by 1H and 13C NMR spectroscopy. From the initial straight portion of the solubility curve (Bs type), the value of the apparent stability constant (Kc) was calculated as 1094 M(-1). The nuclear magnetic resonance studies confirm that GL yields a complex with beta-CD in aqueous medium, which is mainly due to the penetration of the azabicyclooctyl group of GL into the cavity of beta-CD. The study of the monodimensional nuclear Overhauser effect (NOE) of the H3 proton of CD has shown that the tolyl group also interacts with CD, but to a lesser extent than the azabicyclooctyl moiety. Finally, the application of the continous variation technique confirmed the 1:2 drug:CD stoichiometry of the complex.

Cyclodextrins↗
PubMed1996

Dissolution properties and in vivo behaviour of triamterene in solid dispersions with polyethylene glycols.

The applicability of the solid dispersion technique as a method for enhancing the GI absorption of a drug has been explored in order to procure better dissolution characteristics and better bioavailability for triamterene. The physicochemical characterization of the systems has shown the absence of chemical reaction between the drug and the polymers during the solid dispersion elaboration process (melting carrier method). In vitro release profiles have been studied and quantified in terms of dissolution efficiency over the first 30 min (DE30) and dissolution percentage over the first 30 min (DP30). The results have shown that there were no significant differences between the three polyethylene glycols (PEGs) under test. The in vivo effectiveness of the different preparations was also investigated by means of the urinary volumetric excretion (UVE)--pharmacologic effect--and by the estimation of Ke, tmax, and MRT-pharmacokinetic parameters. At end, an analysis of the relative bioavailabilities between formulations has been performed.

Animals↗
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↗
PubMed1996

Relationship between drug percolation threshold and particle size in matrix tablets.

PURPOSE: Since a previous qualitative study carried out by us showed the existence of an important influence of the particle size on the percolation thresholds and taking into account that the existing theoretical models can only provide qualitative explanation to this influence, the purpose of this work is to carry out the first quantitative study of the influence of the particle size over the drug percolation thresholds. METHODS: Matrix tablets have been elaborated using potassium chloride as drug model and Eudragit RS-PM as matrix forming material. Five different KCl particle size fractions have been employed whereas the Eudragit RS-PM particle size was kept constant. In-vitro release assays were carried out for all the elaborated lots. The drug percolation thresholds were estimated following the method proposed by Bonny and Leuenberger. RESULTS: A linear relationship has been found between the drug particle size and the corresponding drug percolation threshold. CONCLUSIONS: This finding confirms the results previously obtained in our qualitative study and has important repercussions in the design of pharmaceutical solid dosage forms. If this linear behaviour is general, the percolation threshold can soon become a useful preformulation parameter.

Chemical Phenomena↗
PubMed1994

A rapid HPLC method for the quantification of tyrothricin, menthol, and benzocaine in pharmaceutical formulations.

A rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, using a stationary phase of alumina particles coated with polybutadiene and an alkaline mobile phase (pH = 8.2). No HPLC method was reported for the analysis of 1. So, this new technique is an alternative to the slow and tedious microbiological methods. On the other hand, it allows the simultaneous quantification of 1, benzocaine (2), and menthol (3), an aromatic compound not currently analyzed by liquid chromatography.

Benzocaine↗