M.A. Holgado

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.

In vitro evaluation of alginate beads of a diclofenac salt

Abstract Alginate beads containing diclofenac hydroxyethylpyrrolidine were formulated with either Eudragit or chitosan in order to achieve an enteric formulation. In all cases, high entrapment efficiencies were obtained. The examination of fractured beads revealed an internal void in the Eudragit–alginate beads. In contrast, a dense homogeneous internal structure was observed in the chitosan–alginate beads due to interpolymeric complex. An interaction between chitosan and drug was also observed. Under conditions mimicking those in the stomach, a small amount of drug was released. The alginate–chitosan beads showed a release behaviour dependent on pH value and alginate–chitosan ratio.

Percolation theory: application to the study of the release behaviour from inert matrix systems

Abstract In the present paper, release profiles obtained from matrix tablets prepared with Eudragit ® RS-KC1 and a usual eccentric machine were studied. The results were in agreement with previously reported release studies for compacts prepared using a hydraulic press. The most outstanding aspect is the study of the influence of the particle size of drug and excipient on the release behaviour of the matrices, and its evaluation on the basis of percolation theory. The influence of soluble drug loading has also been studied. This new theory has been shown to be a useful tool to explain the release profiles from inert matrix compressed tablets.

Synthesis of lidocaine-loaded PLGA microparticles by flow focusing Effects on drug loading and release properties

In the present work, two methods for the preparation of lidocaine-loaded PLGA microparticles are compared. The differences between the polymeric particles obtained by solvent evaporation (SEVM) or flow focusing (FF) were studied by means of scanning electron microscopy and surface thermodynamics determinations. A detailed investigation of the capabilities of the polymer particles to load this drug is described. The physical state of the drug in the polymeric particles and the existence of interactions between both entities were studied by differential scanning calorimetry. The main factors determining the lidocaine incorporation and the release kinetics were the synthesis procedure followed, the amount of drug dissolved in the organic phase during the synthesis routine, the type of polymer (molecular weight and end chemical groups) and the size and the hydrophobic/hydrophilic properties of the particles. The FF technology allowed higher drug incorporations and slower release kinetics. The release studies showed a biphasic profile probably due to diffusion-cum-degradation mediated processes.

Dissolution rate of diazepam from polyethylene glycol 6000 solid dispersions

Abstract A method for the elaboration of solid dispersions, the weight ratios of diazepam to polyethylene glycol 6000 and the particle size of drug in the solid dispersion have been investigated. The preparation method and diazepam-polyethylene glycol 6000 ratio influence the dissolution rate of the drug. It is observed that faster release characteristics were obtained with solid dispersions prepared by the fusion method and by increasing the carrier percentage. The increase in dissolution rate can be considered to result from crystal size reduction and the solubilizing effect of polyethylene glycol 6000. An intrinsic effect of the carrier also increases the dissolution rate of diazepam, since a physical mixture of the same composition dissolves more slowly than the solid dispersions. It is concluded that such a difference must be attributed to a significant reduction of the drug particle size in the carrier matrix.

Physical characterization of carteolol: Eudragit® L binding interaction

Eudragit® L 30D was used as a carrier to prepare carteolol polymeric complexes in order to obtain controlled release dosage forms. The polyanionic form of the polymer, neutralized at different degrees, reacts readily with carteolol hydrochloride to give water-insoluble complexes. Carteolol complexes were characterized by differential scanning calorimetry, IR, 1H- and 13C-NMR spectroscopy. In fact, results indicated that there were intermolecular associations between the polymer and the drug consisting in ammonium salt interactions. Maximum carteolol content was found to be 22% in the complexes.

Drug targeting to cancer by nanoparticles surface functionalized with special biomolecules.

Nanoparticulate-based drug carriers have been developed to overcome the problems of conventional anticancer pharmacotherapy, i.e., the little specificity and low accumulation of the drug into the tumor interstitium, and the extensive biodistribution leading to severe toxicity. Unfortunately, conventional nanoparticles have been demonstrated to merely accumulate the loaded drug into organs associated to the reticuloendothelial system, e.g., the liver. Recently, drug delivery strategies involving the use of nanoplatforms surface decorated with unique biomolecules have demonstrated their potential in concentrating the chemotherapy agent specifically into the malignant cells. This review will be focused on the analysis of the current state of the art and future perspectives of such passive and active targeting strategies based on the enhanced permeability and retention effect and on a ligand-mediated transport, respectively. Special attention will be given to the use of these surface functionalized nanocarriers to overcome multi-drug resistances in cancer cells.

Characterization study of a diclofenac salt by means of SEM and fractal analysis

Abstract In this paper, the morphological and surface characteristics of five samples from different batches of the same salt, diclofenac/ N -(2-hydroxyethyl)pyrrolidine, were investigated using SEM descriptors and fractal dimensions. Two samples were crystallized from organic solvents; the others from water. This elementary difference is suitable to introduce differences in their behaviours. Salt particles obtained from organic solvents present cubic shapes and smooth surfaces. On the other hand, salt particles obtained from aqueous solutions exhibit irregular forms and rugged surfaces. Furthermore, solvent molecules are adsorbed on the particle surface during the synthesis process or become incorporated into the bulk. When these substances are subjected to thermal treatment, the solvent molecules are lost, causing a change in the external morphology of the particles. The fractal dimensions calculated from the slope of a Richardson plot were 1.14, 1.04, 1.09, 1.05 and 1.10. These results seem to indicate that the D values are not greatly affected by the mode of synthesis and solvent employed.

Communications Simultaneous Hplc Determination of some Drugs Commonly Used in Cold Medications: Dextromethorphan, Dephenhydramine, Phenylephrine, Phenylpropanolamine and Pseudoephedrine

AbstractIn the present paper, a simple, direct, accurate and sensitive HPLC method applied over combinations of dextromethorphan, diphenhydramine, phenylephrine, phenylpropanolamine and pseudoephedrine is presented. The use of alumina particles bonded with polybutadiene as stationary phase allows the use of an alkaline mobile phase which provides an important improvement of the assay.

Functional PLGA NPs for oral drug delivery: recent strategies and developments.

This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral bioavailability, the mechanism of each additive.