Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating

The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of manoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage form

Release behavior and bioadhesivity of a hydrophobic polyacid gel

The release behavior of salicylic acid and the bioadhesion properties of crosslinked polyacid hydrophobic-gel disks, containing methyl methacrylate-co-methacrylic acid, were evaluated in simulated fluids. In gastric fluid a very low amount of drug was released with a minimal swelling and water uptake. The drug release was dependent of the drug precipitated in the interconnecting micropores of the disk structure. The transport and release type in this medium ranged from Fickian to zero order depending of drug loading. In intestinal fluid, disks swelled completely and the water absorption capacity was eight-fold its dry weight. In this case the released drug showed a biphasic behavior with a fast linear release (Mt /Mα ≤ 0.6), followed by a slow drug release controlled by the gel swelling. Bioadhesion was measured by the tensiometer method on pig mucosae, the results indicated that these polyacid hydrogels are weak bioadhesives on both gastric and intestinal mucosae.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Colorimetric detection of the potent carcinogen aflatoxin B1 based on the aggregation of L-lysine-functionalized gold nanoparticles in the presence of copper ions

L-lysine functionalized gold nanoparticles (AuNPs-Lys) have been widely used for the detection of worldwide interest analytes. In this work, a colorimetric assay for the detection of the carcinogen aflatoxin B1 (AFB1) based on the aggregation of AuNPs-Lys in the presence of copper ions was developed. For this purpose, AuNPs were synthesized in citrate aqueous solution, functionalized, and further characterized by UV–Vis, fluorescence, Fourier transform infrared spectroscopy (FTIR), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In general, AuNPS-Lys (~2.73 × 1011 particles) offered a clear colorimetric response in the presence of AFB1 and Cu2+ ions showing linearity in the range of 6.25 to 200 ng AFB1/mL, with a detection limit of 4.18 ng AFB1/mL via photometric inspection. Moreover, the performance of the proposed methodology was tested using the 991.31 AOAC official procedure based on monoclonal antibodies in maize samples artificially contaminated with AFB1. There was a good agreement between the measured AFB1 concentrations in both assays, the average recoveries for the colorimetric and immunoaffinity assays were between 91.2–98.4% and 96.0–99.2%, respectively. These results indicated that the colorimetric assay could be used as a rapid, eco-friendly, and cost-effective platform for the quantification of AFB1 in maize-based products

La terapia a nanoescala: ensamblaje de estructuras liberadoras de fármacos

RESUMEN: La nanotecnología es una ciencia que posee grandes expectativas en diversas áreas, pues contempla la obtención de bloques de materia muy pequeños, creados a nivel molecular o atómico, para el desarrollo de nuevos dispositivos o materiales con propiedades mejoradas. Una de las aplicaciones más prometedoras de la nanotecnología es la nanomedicina, la cual involucra el desarrollo de nanosistemas diseñados para monitorear la salud, liberar fármacos, curar enfermedades o reparar tejidos. Respecto a la liberación de fármacos, ésta se ha asentado en el antiguo concepto de la “bala mágica”, en el que se establece una búsqueda de diminutas partículas o nanoacarreadores capaces de dirigir sustancias activas al sitio donde son requeridas, con el objetivo de mantener y controlar la entrega del fármaco en tiempo y espacio. La intensa investigación de las últimas tres décadas ha demostrado que los nanoacarreadores cumplen con esas expectativas y representan una mejor respuesta para atender las necesidades terapéuticas actuales

Adaptation and optimization of the emulsification-diffusion technique to prepare lipidic nanospheres

In this study, the emulsification-diffusion method traditionally used to prepare polymeric nanoparticles was adapted to obtain lipidic nanospheres (LN) using four model lipids. The method consists of dissolving the lipid in a partially water-miscible solvent (previously saturated with water) at room temperature or at controlled temperature depending on lipid solubility. This organic phase is emulsified in an aqueous solution of a stabilizing agent (saturated with solvent) by conventional stirring at the same temperature used to dissolve the lipid. This oil-in-water emulsion is then diluted with an excess of water at controlled temperature in order to provoke the diffusion from the internal phase into the external phase thereby causing lipid aggregation in the form of LN. This new approach for the preparation of LN has clear advantages over the existing methods, namely: (i) it is efficient and versatile; (ii) easy implementation and scaling up (with no need of high energy sources); (iii) high reproducibility and narrow size distribution; (iv) less physical stress (i.e., long exposure to high temperatures and to mechanical dispersion); (v) it is not necessary to dissolve the drug in the melted lipid. The selection of the water-miscible solvent and the stabilizers are critical parameters to obtain lipidic particles in the nanometric range. In general, solvents with high water miscibility and stabilizers able to form stable emulsions are preferred. The results demonstrated that it was possible to reduce the particle size by increasing the process temperature, the stirring rate, the amount of stabilizer, and by lowering the amount of lipid. Control of the preparative variables allowed to obtain LN with diameters under 100 nm. It was found that the influence of preparative parameters was associated with a mechanism based on a physicochemical instability. In this sense, it is suggested that the rapid solvent diffusion produces regions of local supersaturation near the interface, and LN are formed due to the ensuing interfacial phase transformations and lipid aggregation that occur in these interfacial domains. In terms of stability, only poly(vinyl alcohol) (PVAL) was able to preserve the physical stability of the dispersion for long periods after preparation. This effect was attributed to the ability of PVAL chains to form a strongly attached layer on the nanoparticle surface with an excellent repulsion effect

Relationship between the swelling process and the release of a water-soluble drug from a compressed swellable-soluble matrix of poly(vinyl alcohol)

An attempt was made in this study to relate the release of a highly water-soluble model drug from tablet matrices of poly(vinyl alcohol) (PVAL) with the factors that may affect the release behavior. Swelling was evaluated using a simple projection method. The swollen layer was photographed to monitor its thickness. The polymer and drug dissolution were determined simultaneously by spectrophotometric methods. The resulting change of tablet area showed that the process of swelling occurred in three different stages that were intimately related to polymer dissolution: (a) a rapid initial swelling, resulting in an increased area; (b) a period with an approximately constant area; and (c) a decrease of the tablet area. In spite of the significant dissolution of PVAL during the release process, the thickness of the gel layer gradually increased. Thus, the delivery was governed by the drug concentration gradient along the diffusional path length. The drug release appeared to be controlled by a diffusion process according to Higuchi-type kinetics. The data analysis of drug and polymer profiles confirmed the diffusional mechanism

PREPARACIÓN Y EVALUACIÓN IN VITRO DE NANOPARTÍCULAS POLIMÉRICAS BIODEGRADABLES COMO AGENTE DE CONTRASTE PARA ULTRASONIDO

Los agentes de contraste para ultrasonido hasta ahora disponibles en el mercado, no permiten la detección eficiente de tumores en diversos órganos, la miniaturización de este tipo de sistemas a escala nanométrica podría resolver este problema. La finalidad de este trabajo fue la adaptación del método de desplazamiento de solvente que permitiera la preparación de nanopartículas "huecas", a partir de la encapsulación de un núcleo sublimable (naftaleno), para después caracterizarlas desde el punto de vista de tamaño, densidad y morfología, así como llevar a cabo su evaluación in vitro mediante un sistema de ultrasonido comercial. Las nanopartículas preparadas tuvieron un diámetro entre 50-400 nm logrando una eficiencia de entrampamiento del 66.55% de naftaleno. Mediante liofilización se retiró un 98% de la cantidad de naftaleno encapsulada, sin embargo, de acuerdo con las micrografías obtenidas por microscopía electrónica de barrido y de transmisión no se evidenció la presencia de huecos en la matriz polimérica además la densidad fue similar para las reparaciones con naftaleno y nanoesferas formadas únicamente con polímero, por otro lado, los resultados de la evaluación in vitro sugieren un aumento en la ecogenicidad de las preparaciones que contienen nanopartículas, en comparación con aquellas soluciones en donde no están presentes

Influence of the stabilizer coating layer on the purification and freeze-drying of poly(D, L-lactic acid) nanoparticles prepared by an emulsion-diffusion technique

In this study, the purification by cross-flow filtration (CFF) and freeze drying of poly(D, L-lactic acid) (PLA) nanoparticles prepared by an emulsion-diffusion technique using poly(vinyl alcohol) (PVAL) or poloxamer 188 (P-188) were investigated. The stability of the suspensions was correlated to the affinity of the stabilizers for the nanoparticle surface, the resistance of the coating layer to continuous filtration and to freeze-thawing procedures. The results indicated a clear difference between the two stabilizers, suggesting that the nature of the coating layer has a very important role during CFF and freeze-drying. Nanoparticles prepared with PVAL were filtered and freeze-dried without nanoparticle fusion. This behaviour was attributed to the formation of a stable thick layer (similar to that found for polystyrene latex). In contrast, aggregation of nanoparticles was observed during CFF for the batches prepared with P-188, indicating that the polypropylene oxide blocks present in the copolymer have little affinity for the PLA surface. However, these suspensions were successfully recovered when using stabilizer solutions as diafiltration media, suggesting a dynamic exchange between the P-188-adsorbed chains and those of the identical polymer remaining in the bulk solution. The presence of P-188 did not prevent nanoparticle aggregation after freeze-drying. Therefore the use of cryoprotectants was necessary. Aggregation may have been due to an increase in the solubility of P-188 in the bulk solution, which provokes a destabilization of the suspension by desorption and partial coverage of the surface. The best cryoprotectants were found to be sugars containing glucose units. The cryoprotective effect was related to the hydrogen bonding capability of these sugars, which prevented aggregation by dehydration of P-188 forcing it to the PLA surface