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The aim of the present study was to evaluate the influence of the incorporation of caffeine as a model active ingredient on the quality attributes of a bioadhesive emulgel formulation previously optimized by Quality by Design (QbD) tools. Emulgels are emerging topical drug delivery systems for cosmetic or pharmaceutical uses, which combine the advantages of both emulsions and gels.In this work, the observed and predicted values for spreadability, phase separation by centrifugation and detachment forces performed by texturometer were compared with those of the control and active-containing emulgel formulations. In addition, rheological properties, release of caffeine and comparative in vitro/ex vivo bioadhesion properties were evaluated using human skin.The flow curves of emulgel formulations showed the typical pseudoplastic and no thixotropic flow with yield stress. The incorporation of active ingredient did not produce significant changes. All emulgels were uniformly spread and no significant differences in spreadability values between control and caffeine containing formulations and neither respect to those predicted values from experimental design optimization were found. Emulgel formulations showed appropriate detachment forces values and no significant differences between caffeine loading and control emulgel formulations were observed.Caffeine was successfully vehiculized in this optimized bioadhesive emulgel formulation, which showed high robustness regarding the process variability. There were no significant changes in the critical quality attributes after the incorporation of the active ingredient and a promising stability was observed for at least one year. Results suggested that the optimized emulgel is an interesting topical biodhesive delivery system for cosmetic applications, including agents for skin conditioning, not present in gels formulations.OBJECTIF: la présente étude visait à évaluer l’influence de l’incorporation de la caféine comme une substance active modèle dans les attributs de qualité d’une préparation d’émulgel bioadhésif préalablement optimisée grâce à des outils QbD (Quality by Design, Qualité par la conception). Les émulgels sont des systèmes d’administration de médicaments topiques émergents destinés à des usages cosmétiques ou pharmaceutiques, qui associent les avantages des émulsions et des gels. MÉTHODES: dans cet étude, les valeurs observées et prédites en matière d’étalement, de séparation des phases par centrifugation et de forces de détachement par texturomètre ont été comparées à celles des préparations de contrôle et d’émulgel contenant des actifs. En outre, les propriétés rhéologiques, la libération de caféine et la comparaison des propriétés de bioadhérence in vitro / ex vivo ont été évaluées sur la peau humaine. RÉSULTATS: les courbes de débit des préparations d’émulgel révèlent un flux pseudoplastique typique et non thixotropique avec charge d’écoulement. L’incorporation de la substance active n’a pas produit de changements importants. Tous les émulgels ont été uniformément étalés et aucune différence significative dans les valeurs d’étalement entre les préparations de contrôle et celles contenant de la caféine n’a été observée. Aucune différence concernant les valeurs prédites dans l’optimisation de la conception expérimentale n’a été observée. Les préparations d’émulgel ont montré des valeurs de forces de détachement appropriées et aucune différence significative n’a été observée entre les préparations d’émulgel à base de caféine et les préparations de contrôle. CONCLUSION: la caféine a été administrée avec succès dans cette préparation optimisée d’émulgel bioadhésif, qui a affiché une grande résistance en ce qui concerne la variabilité du procédé. Il n’y a pas eu de changement significatif dans les attributs de qualité critiques après l’incorporation de la substance active et une stabilité prometteuse a été observée pendant au moins un an. Les résultats ont suggéré que l’émulgel optimisé est un système d’administration de bioadhérence topique intéressant pour les applications cosmétiques, y compris les agents de revitalisation de la peau qui ne se trouvent pas dans les préparations de gels.

Background: Mathematical modeling in modified drug release is an important tool that allows predicting the release rate of drugs in their surrounding environment and elucidates the transport mechanisms involved in the process. Objective: The aim of this work was to develop a mathematical model that allows evaluating the release profile of drugs from polymeric carriers in which the swelling phenomenon is present. Methods: Swellable matrices based on ionic complexes of alginic acid or carboxymethylcellulose with ciprofloxacin were prepared and the effect of adding the polymer sodium salt on the swelling process and the drug release was evaluated. Experimental data from the ciprofloxacin release profiles were mathematically adjusted, considering the mechanisms involved in each stage of the release process. Results: A proposed model, named “Dual Release” model, was able to properly fit the experimental data of matrices presenting the swelling phenomenon, characterized by an inflection point in their release profile. This entails applying the extended model of Korsmeyer-Peppas to estimate the percentage of drug released from the first experimental point up to the inflection point and then a model called Lumped until the final time, allowing to adequately represent the complete range of the drug release profile. Different parameters of pharmaceutical relevance were calculated using the proposed model to compare the profiles of the studied matrices. Conclusion: The “Dual Release” model proposed in this article can be used to predict the behavior of complex systems in which different mechanisms are involved in the release process.

Drug delivery by layered double hydroxides (LDHs) is extensively studied due to the capacity of these solids to preserve the active agent and to modify its release rate and bioavailability. In this work, an ibuprofen–LDH complex was synthesized with high drug content (54% w/w), incorporated both in the interlayer and on the surface. The mechanisms involved in the ibuprofen release process were studied as a function of the anion type (chloride, acetate, and phosphate) and concentration, and the pH of the release media. The experimental conditions selected were based on the composition of pharmaceutically relevant fluids such as gastric, intestinal and lysosomal simulated media. Three release mechanisms accounted for the rate and extent of the drug release: ion exchange (highly dependent on the anions), desorption and weathering (dependent on the pH). These mechanisms, together with the different solubility of the anionic and non-ionic ibuprofen species, also explained the release behavior for particulate solid and hydrogel formulations. Anion exchange determined ibuprofen release in intestinal medium (phosphate anions pH 6.8) whereas surface reactions mediated by solid weathering or drug solubility ruled the release in acid media (gastric fluid and lysosomal medium).

This article reports dynamic light scattering (DLS) data, and electrokinetic � -potentials of aqueous dispersions of two linear flexible polymethacrylic acid derivatives Eudragit ® L100 (EuL) and S100 (EuS) loaded with two model drugs (D), lidocaine (Ld) and atenolol (At). Dispersions of EuL and EuS at 1,0 % neutralized with increasing percentages (50, 75 and 100 mole %) of each D exhibited a unimodal scattering distribution rendering diffusion coefficients (DC) in the interval of 4 to 9. 10 -9 cm 2 /s. All dispersions 50% neutralized exhibited quite similar DC. However, the effect of in- creasing neutralization followed a different pattern in each Eudragit ® . All dispersions exhibited high negative � -potentials that were lower at 100% with respect to 50% loading. Both, DC and � -potentials, of redispersed lyophilized samples of (EuL-D) and (EuS-D) remained identical to those of in situ prepared while those of analog samples prepared by solvent evaporation exhibited some slight differences. The behavior of (EuL-D) and (EuS-D) systems examined here through DLS appears to be quite similar to that reported for polyelectrolytes neutralized with monovalent inorganic cations. Last, it has been shown that DLS provides valuable information about the reversibility from solid to dispersion states of these nanometric drug carrier systems.

The current study is focused on physicochemical characterization and in vitro drug delivery evaluation ofself-organized nanoparticles based on drug-interpolyelectrolyte complexes (DIPEC). The interactionbetween two oppositely charged polymethacrylates, Eudragit® EPO and L100, and four non-steroidalanti-inflammatory drugs, Salicylic Acid, Benzoic Acid, Ketoprofen and Naproxen was studied.DIPEC nanoparticles produce translucent and stable aqueous dispersions where a remarkably highproportion of drug (between 57 and 95%) is condensed with polyelectrolyte (PE) under the form of ionicpairs. They exhibited particle size in the range of 120e198 nm and high positive zeta potential,contributing to physical stability. The sign of zeta potential shifted from positive to negative by changesin composition of DIPEC. Thermal analysis and X-ray diffraction patterns of freeze dried DIPEC showedthe amorphous state of products and the complete interaction of PE and drug. Solid complexes wereeasily redispersed in water yielding nearly the same parameters of fresh dispersions. In vitro releaseexperiments showed that DIPEC nanodispersions behave as drug reservoirs, exhibiting a slow drugrelease rate in water, which significantly increased in simulating physiological fluids, promoted by ionicexchange. They also exhibited a remarkable robustness towards simulated physiological media ofdifferent pH. Fil: Palena, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Potential applications in drug delivery from nanostructures composed of two oppositely charged polymethacrylates, eudragit L100 (EL) and eudragit EPO (EE), loaded with three model basic drugs (D), atenolol, propranolol, and metroclopramide were evaluated. The self-organized nanoparticles based on drug-interpolyelectrolyte complexes (DIPEC), (EL-D50)-EEX, were obtained by mixing the aqueous dispersions of both polyelectrolytes at room temper- ature in an ultrasound bath. Dispersions of (EL-D50) neutralized with increasing proportions of EE exhib- ited a rise of turbidity, particle sizes in the range of 150-400 nm, and high negative zeta potential. The sign of zeta potential was shifted from negative to positive by changes in composition of DIPEC. Freeze dried DIPEC were easily redispersed in water yielding nearly the same parameters of fresh dispersions. In vitro release experiments using Franz cells showed that DIPEC systems behave as a drug reservoir that slowly releases the drug as water is placed in the receptor compartment. The release rate was raised by ionic exchange with counterions present in simulated physiological fluids placed in the receptor media. Delivery of D from DIPEC exhibited a remarkable robustness toward simulated physiological media of different pH. The DIPEC systems exhibit interesting properties to design nanoparticulate drug delivery systems for oral and/or topical routes.