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 nanoparticles. 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 forms.

Effect of nanoparticle size on the extravasation and the photothrombic activity of meso(p-tetracarboxyphenyl)porphyrin.

Particle size should be optimized to achieve targeted and extended drug delivery to the affected tissues. We describe here the effects of the mean particle size on the pharmacokinetics and photothrombic activity of meso-tetra(carboxyphenyl)porphyrin (TCPP), which is encapsulated into biodegradable nanoparticles based on poly(d,l-lactic acid). Four batches of nanoparticles with different mean sizes ranging from 121 to 343 nm, were prepared using the emulsification-diffusion technique. The extravasations of each TCPP-loaded nanoparticle formulation from blood vessels were measured, as well as the extent of photochemically induced vascular occlusion. These preclinical tests were carried out in the chorioallantoic membrane (CAM) of the chicken's embryo. Fluorescence microscopy showed that both the effective leakage of TCPP from the CAM blood vessels and its photothrombic efficiency were dependent on the size of the nanoparticle drug carrier. Indeed, the TCPP fluorescence contrast between the blood vessels and the surrounding tissue increased at the applied conditions, when the particle size decreased. This suggests that large nanoparticles are more rapidly eliminated from the bloodstream. In addition, after injection of a drug dose of 1mg/kg body weight and a drug-light application interval of 1 min, irradiation with a fluence of 10J/cm(2) showed that the extent of vascular damage gradually decreased when the particle size increased. The highest photothrombic efficiency was observed when using the TCPP-loaded nanoparticles batch with a mean diameter of 121 nm. Thus, in this range of applied conditions, for the treatment of for instance a disease like choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), these experiments suggest that the smallest nanoparticles may be considered as the optimal formulation since they exhibited the greatest extent of vascular thrombosis as well as the lowest extravasation.