PubMed Health⌕ Search

Biomedical subjects

I Caraballo

Publications and source records attributed to I Caraballo.

13 recordsLinked to original sources
PubMed2002

Stability study of flutamide in solid state and in aqueous solution.

A high-performance liquid chromatography (HPLC) assay has been developed for the determination of flutamide and its degradation products. Using this method, the influence of important formulation factors on the stability of flutamide has been estimated. The stability studies have been carried out in solid state as well as in aqueous solution. The results obtained have shown a good stability for flutamide in solid state. This drug remained practically unchanged after a four-month assay in adverse temperature and humidity conditions. On the other hand, the results obtained from the stability study in solution during 12 days have shown that flutamide in aqueous solution underwent a clear degradation at mean or high temperature (22 degrees C, 37 degrees C) and acidic pH conditions (1.1). With respect to the influence of ionic strength, it has been found that the presence of sodium chloride prevents the degradation of flutamide in aqueous solution. The second-order kinetics model provides the best fit for highly degraded solutions.

Analysis of Variance↗
PubMed2001

Functional regeneration in a rat Parkinson's model after intrastriatal grafts of glial cell line-derived neurotrophic factor and transforming growth factor beta1-expressing extra-adrenal chromaffin cells of the Zuckerkandl's organ.

Intrabrain transplantation of chromaffin cell aggregates of the Zuckerkandl's organ, an extra-adrenal paraganglion that has never been tested for antiparkinsonian treatment, induced gradual improvement of functional deficits in parkinsonian rats. These beneficial effects were related to long survival of grafted cells, striatal reinnervation, and enhancement of dopamine levels in grafted striatum. Grafted cells were not dopaminergics, but they expressed glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta(1). These factors were detected in the host striatal tissue, indicating that chromaffin cells secreted them after grafting. Because glial cell line-derived neurotrophic factor possesses neurorestorative properties over dopaminergic neurons, and transforming growth factor-beta(1) is a cofactor that potentiates the neurotrophic actions of GDNF, functional regeneration was likely caused by the chronic trophic action of neurotrophic factors delivered by long-surviving grafted cells. This work should stimulate research on the clinical applicability of transplants of the Zuckerkandl's organ in Parkinson's disease.

Adrenal Medulla↗
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↗
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

Statistical optimization of a sustained-release matrix tablet of lobenzarit disodium.

The statistical optimization of sustained-release matrix tablets of lobenzarit disodium salt (LDS) was performed using the central composite experiment design 2(3) for three independent variables: the amount of polymer (Eudragit RS-PO) AP, the total volume of granulation solvent VS, and the amount of filler (microcrystalline cellulose) CE. The t90% was selected as the response variable. The response surfaces were performed from a statistical mathematical model. The optimal formulation was obtained for the variables (AP = 15 mg, VS = 60 microliters, and CE = 0).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Preclinical study of an oral controlled release naltrexone complex in mice.

Naltrexone, a long-acting, orally effective, opioid antagonist which blocks opioid effects as well as the development of physical dependence, would appear to be a drug ideally suited to addiction treatment. An optimal dosage regimen is critical for the treatment patient compliance in ambulatory opiate detoxification programs. The ideal dosage regimen would be an oral controlled-release system of naltrexone that allowed once-a-day administration providing stable plasma levels. A naltrexone-Eudragit L complex was produced in aqueous medium from naltrexone hydrochloride solution and Eudragit L30D (30% w/v) previously diluted (6% w/v) and partially neutralized. The antagonistic activity of naltrexone-Eudragit L on morphine-induced thermal antinociception, in comparison with conventional naltrexone, was evaluated, using the mouse hot-plate model. Mice were administered 10 mg kg(-1) morphine subcutaneously, 10 min before test, and the antagonist products, either naltrexone-Eudragit L or naltrexone hydrochloride, were administered orally at 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16h before the test. The results showed that the antagonism induced by naltrexone-Eudragit L was effective until 12 h after drug administration, while that induced by naltrexone hydrochloride disappeared 10 h after its administration. A 23.47% increase of the area under curve was obtained when naltrexone-Eudragit L was administered, compared with that induced by conventional naltrexone. The time taken to decrease the inhibition of analgesic activity to 50% was delayed by 51.80%. This complexation technique can be considered as a useful tool in the design of oral controlled-release systems capable of inducing a long-lasting effect in-vivo.

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

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↗
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↗
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↗
PubMedDate not supplied

[Natural "dopaminotrophic" cell transplant: a new concept in antiparkinsonian therapy].

AIM AND METHOD: Parkinson s disease is caused by the degeneration of dopaminergic neurons of substantia nigra projecting to striatum. Cellular substitution represents a potentially treatment once beneficial levodopa effects wear off. A promising therapeutic approach is grafting cells or other vectors which release neuroprotective molecules that stimulate regeneration in the damaged nigrostriatal system or, in other words, that exert a dopaminotrophic action. We have tested the suitability of intrastriatal grafts of extra adrenal chromaffin cells taken from the Zuckerkandl s organ. This paraganglion contains chromaffin cells that express and release glial cell line derived neurotrophic factor (GDNF) and transforming growth factor b1 (TGF b1), both known to protect dopamine cells in vitro and in vivo. Grafts induced a functional recovery of parkinsonian rats which developed over months. The beneficial effects of grafts of the Zuckerkandl s organ were related to long survival of grafted cells, striatal reinnervation, enhancement of dopamine levels in the host striatum, and the cell delivery into the host striatum of GDNF and TGF b1. CONCLUSION: Our result should stimulate research on the clinical applicability of transplants of the Zuckerkandl s organ in Parkinson s disease

Animals↗