Biomedical subjects

A A C C Pais

Publications and source records attributed to A A C C Pais.

8 recordsLinked to original sources

PubMed2006

Interaction of omeprazole with a methylated derivative of beta-cyclodextrin: phase solubility, NMR spectroscopy and molecular simulation.

PURPOSE: Cyclodextrins are known to be good solubility enhancers for several drugs, improving bioavailability when incorporated in pharmaceutical formulations. In this work we intend to assess and characterize the formation of inclusion complexes between omeprazole (OME) and a methylated derivative of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD). A comparison with results obtained from the most commonly used natural cyclodextrin, beta-cyclodextrin (betaCD) is also presented in most cases. MATERIALS AND METHODS: The interaction of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase solubility studies, 1D (1)H and 2D rotating frame nuclear overhauser effect NMR spectroscopy (ROESY) and Molecular Dynamics. RESULTS: The solubility of OME was significantly increased by formation of inclusion complexes with each cyclodextrin. Phase solubility studies and continuous variation plots revealed that OME forms an inclusion complex in a stoichiometry of 1:1 with both cyclodextrins. (1)H NMR and ROESY spectra of the inclusion complexes indicated that the benzimidazole moiety is included within the cyclodextrins cavities. Molecular dynamics showed that OME is more deeply included in the MbetaCD than in betaCD cavity, in agreement with a larger apparent stability constant (K (S)) obtained for the inclusion complex with MbetaCD. CONCLUSIONS: MbetaCD proved to be an efficient enhancer of OME solubility, thus possessing characteristics for being an useful excipient in pharmaceutical formulations of this drug.

Chemical Phenomena↗

PubMed2006

Polyelectrolytes in solutions with multivalent salt. Effects of flexibility and contour length.

It has been experimentally observed that trivalent ions are capable of promoting compaction of semi-flexible polyelectrolyte chains. In this work we perform Monte Carlo simulations on single chain model systems with varying chain size and stiffness and evaluate the action of multivalent salt on the chain conformation. It is observed that longer chains tend to achieve relatively more compact conformations than shorter ones, and the dimensions of the collapsed structures do not significantly vary with contour length. The influence of contour length and intrinsic stiffness in the process of ion condensation is studied by analysis of the ion-ion nearest-neighbor distribution. The general trend is an increase of the degree of ion condensation as the chain length increases, in accordance with experimental evidence. A decreased importance of end-effects and, especially, larger volume charge densities are responsible for such behavior. The influence of chain stiffness is nontrivial, and depends on salt concentration. The results emphasize the complex nature of ion-correlation phenomena in flexible or semi-flexible chains and call for the development of more sophisticated analytical theories.

Complex Mixtures↗

PubMed2006

Thermal behaviour of human stratum corneum. A differential scanning calorimetry study at high scanning rates.

PURPOSE: To use high-speed differential scanning calorimetry (DSC) in the identification of transitions in human stratum corneum (SC). Several scanning rates (100 degrees C/min to 400 degrees C/min) are used. RESULTS: Eight transitions from 0 to 120 degrees C are detected in a significant number of samples. Most of these transitions have already been identified in previous studies, but have been labeled considering essentially that only four are present. Results also indicate some degree of reversibility for transitions occurring at temperatures above 90 degrees C. Dehydrated SC samples displayed slightly more defined transition peaks and a less frequent presence of the transitions below 50 degrees C. In turn, the delipidised SC matrix showed two major endothermic signals, centered around 55 and 100 degrees C, in conjunction with other much less marked features. CONCLUSIONS: The interpretation of DSC traces in terms of four main transition temperatures must be complemented having in mind the occurrence of other transitions, some of them at physiological temperatures. This work further suggests that transitions at temperatures above 90 degrees C may to a large degree be associated to lipids, while transition at approx. 55 degrees C is probably related to lipids covalently linked to proteins, as previously suggested.

Adult↗

PubMed2006

Study of human stratum corneum and extracted lipids by thermomicroscopy and DSC.

A study on the thermal behavior of human stratum corneum and lipids is described. The use of high scanning rate DSC for both SC and extracted lipids allows the consistent determination of transition temperatures, including those of lower energy. Changes are found both at physiological and higher temperatures. There is a clear correspondence between the thermotropic behavior of these two systems. However, one of the transitions found in human SC (approximately 55 degrees C) is absent in extracted lipids and may be ascribed to those covalently-linked to corneocytes. Lipidic thermotropic behavior is clearly found above 100 degrees C, in which proteins do not play an exclusive role. Changes related to most transitions are observed directly by polarized light thermal microscopy in extracted lipids. This technique also allowed for the observation of large segregated domains in the extracted lipids. A drastic change is observed at approximately 60 degrees C, corresponding to the disruption of the lamellar structure.

Calorimetry, Differential Scanning↗

PubMed2005

Polyion adsorption onto catanionic surfaces. A Monte Carlo study.

The adsorption of a single and negatively charged polyion with varying flexibility onto a surface carrying both negative and positive charges representing a charged membrane surface has been investigated by using a simple model employing Monte Carlo simulations. The polyion was represented by a sequence of negatively charged hard spheres connected with harmonic bonds. The charged surface groups were also represented by charged hard spheres, and they were positioned on a hard surface slightly protruding into the solution. The surface charges were either frozen in a liquidlike structure or laterally mobile. With a large excess of positive surface charges, the classical picture of a strongly adsorbed polyion with an extended and flat configuration emerged. However, adsorption also appeared at a net neutral surface or at a weakly negatively charged surface, and at these conditions the adsorption was stronger with a flexible polyion as compared to a semiflexible one, two features not appearing in simpler models containing homogeneously charged surfaces. The presence of charged surface patches (frozen surface charges) and the ability of polarization of the surface charges (mobile surface charges) are the main reasons for the enhanced adsorption. The stronger adsorption with the flexible chain is caused by its greater ability to spatially correlate with the surface charges.

Adsorption↗

PubMed2005

Polymer distribution in connected spherical domains.

The distribution of neutral and charged polymers with different flexibilities between two spheres of varying volume connected by a short and narrow cylinder has been investigated by Monte Carlo simulations. The uncharged chain displayed mostly a single-sphere occupancy due to the high conformational entropy penalty of crossing the cylindrical domain, whereas for the charged polymer a double-sphere occupancy was obtained, except for very different spherical volumes. The origin of this different occupancy behavior stems from the counterion entropy. At increasing stiffness, a stronger preference for double-sphere occupancy was predicted.

Journal Article↗

PubMed2004

Analysis of formulation effects in the dissolution of ibuprofen pellets.

In this work the effects of citric acid and of two common fillers, lactose (soluble) and tricalcium phosphate (insoluble) are examined on the release profiles from pellets, using ibuprofen as a model drug with pH-dependent solubility. Also studied is the dependence of these profiles on the specific surface area, bulk density, apparent density, porosity and porosity parameters (pore size distribution, total pore surface area, mean pore diameter and pore shape), as determined by mercury intrusion porosimetry. Pellets with high porosity and total pore surface area but small median pore diameter (tricalcium phosphate pellets-IPM) are found to produce similar dissolution results to those of low porosity and low total pore surface area, but having a high median pore diameter (lactose pellets-ILM), irrespective of the solubility of excipients. Addition of citric acid causes a delay in the initial dissolution for both formulations. During dissolution, however, citric acid reduces the median pore diameter of lactose-based pellets. In contrast, in tricalcium phosphate/citric acid pellets (CIPM), this parameter increases considerably during dissolution, when compared to the IPM formulation. These findings may justify the contrasting dissolution behaviors of CIPM and CILM (lactose/citric acid) pellets, after their common behavior in the initial stages, and show that porosity and its related parameters, along with physical properties of excipients such as solubility, density and specific surface area, are helpful to predict pellet behavior in drug release profiles.

Calcium Phosphates↗

PubMed2003

Comparison of dissolution profiles of Ibuprofen pellets.

In this work we use both model dependent and independent techniques to assess the difference between dissolution profiles in which ibuprofen, in the form of uncoated pellets, is used as a model drug. The choice of a proper regression function, the relevance of the estimated parameters and the influence of the choice of dissolution points in the assessment of differences is discussed. The results obtained via mean dissolution times (MDT) and fit-factors (f(1) and f(2)) are also discussed and a non-quantitative method based on profiles correlation with graphical representation (concentration vs. concentration and rate vs. rate) presented. The tested methods discriminate similarly between curves, although not in all cases, but those based on modeling, MDT and fit-factors have shown to be less informative than the correlation approach.

Drug Implants↗