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One of the possible causes of failure of the mechanochemical activation of poorly soluble drugs relies on the scarce drug wettability. Indeed, the mechanochemical process comports the disposition of drug nano-crystals and amorphous drug, generated by the destruction of original drug macro-crystals, on the surface of the carrier (acting as stabiliser), usually represented by crosslinked polymeric particles. Accordingly, the scarce drug wettability can reduce the beneficial action of mechanochemical activation (nano-crystals and amorphous drug are characterised by a higher solubility with respect to the original macro-crystals). In this light, this paper is focussed on the use of surfactants for the increase of delivery system (drug plus carrier) wettability. In particular, the surfactant-polymer systems are characterised for what concerns their bulk and surface properties. This allows to select the best surfactant and to experimentally verify its effect on the release kinetics of a poorly soluble and wettable drug. [ABSTRACT FROM AUTHOR]

Abstract: The analysis of the release kinetics from a delivery system containing amorphous and/or nano-crystalline drug requires the evaluation of many parameters among which the water solubility of the amorphous/nano-crystalline drug is one of the most important. This, in turn, needs the determination of the drug melting enthalpy/temperature dependence on the curvature radius of the crystalline phase (thought, for the sake of simplicity, of spherical shape). Accordingly, this paper is aimed to develop a general theoretical approach devoted to model the melting enthalpy/temperature variation with nano-crystals radius, the solubility dependence on nano-crystals radius and the release process from an ensemble of polymeric particles (crosslinked polyvinylpyrrolidone) containing a poorly water soluble drug (nimesulide) in its amorphous and nano-crystalline status. Drug loading was achieved by means of drug and polymer co-grinding. This study allowed the determination of the nanocrystals fraction and size distribution in the co-ground systems, the drug solubility increase of nano-crystals and the estimation of amorphous drug solubility. This approach yielded to the conclusion that, in the case of nimesulide, a significant increase of solubility occurs for the amorphous form and for nanocrystals characterised by radii lower than 4nm. [Copyright &y& Elsevier]

This paper focuses on the experimental and theoretical study of drug release from microemulsions structured as a dispersion of oil droplets in water or vice versa. In particular, drug release kinetics is studied by means of permeation experiments where a synthetic thin (149 μm) membrane separates the donor compartment, filled by the drug-loaded microemulsion, from the receiver one, filled by a drug-free aqueous-phase. Experimental trials evidences a peculiar release kinetics resembling that typical of permeation through a thick membrane where the permeated drug amount shows a not linear trend with time. This phenomenon is explained supposing the existence of an interaction between the drug and the surfactant micelles pervading the microemulsion aqueous-phase. This hypothesis is supported by independent experimental tests (critical micellar concentration measurements and release tests from a microemulsion containing small amounts of drug and surfactant) and by means of a mathematical model describing the whole permeation phenomenon.Nimesulide (anti-inflammatory action) is chosen as model drug for its industrial relevance while isopropyl myristate (oil-phase), benzyl alcohol (co-surfactant), Tween 80 (surfactant), compose our microemulsion (45.7% (w/w) water, 30.8% (w/w) surfactant, 11.75% (w/w) oil-phase and 11.75% (w/w) co-surfactant).The results of CMC measurements, release tests from low drug content microemulsion jointly with the good model data fitting ensure about the reliability of our hypothesis. [Copyright &y& Elsevier]