Synthesis and characterization of novel dextran-conjugated macromolecules of aceclofenac

The study involves the condensation of acylimidazole derivatives of acaclofenac (AC) with dextran 10,000 and 20,000 to obtain aceclofenac-dextran prodrugs AC10 and AC20 respectively with an aim to improve aqueous solubility, increase therapeutic efficiency and reduce the gastrointestinal side effects. The structure of synthesized prodrugs was confirmed by IR and NMR spectroscopy. The molecular weight was determined by Mark-Howink Sakurada equation and the degree of substitution was obtained as 13.3 and 16 % for the prodrugs. In vitro hydrolysis carried out in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF) showed faster hydrolysis in SIF and SCF. The percentage anti-inflammatory activity of AC was found as 49.56 whereas an improved value of 56.44 and 61.82 % were obtained for AC10 and AC20 respectively. The prodrugs showed improved analgesia and reduced ulcerogenicity than aceclofenac, thereby proving to be better in action than the parent drug(AU)

El estudio se centra en la condensación de acilimidazoles derivados de aceclofenaco (AC) con dextrano 10.000 y 20.000 para obtener los profármacos de aceclofenaco-dextrano AC10 y AC20, respectivamente, con el objetivo de mejorar la hidrosolubilidad, aumentar la eficacia terapéutica y reducir los efectos secundarios gastrointestinales. La estructura de los profármacos sintetizados se ha confirmado a través de espectroscopia IR y RMN. El peso molecular ha sido determinado a través de la ecuación de Mark-Houwink-Sakurada y se ha obtenido un grado de sustitución de 13,3 y 16% para los profármacos. La hidrólisis in vitro llevada a cabo en fluido gástrico simulado (FGS), fluido intestinal simulado (FIS) y fluido colónico simulado (FCS) ha mostrado una hidrólisis más rápida en FIS y FCS. De ello ha resultado un porcentaje de actividad antiinflamatoria de AC de 49,56, mientras que para AC10 y AC20 se ha obtenido un valor aumentado de 56,44 y 61,82% respectivamente. Los profármacos han mostrado una mejor analgesia y una menor ulcerogenicidad que el aceclofenaco, por lo que se demuestra que su acción es mejor que la del fármaco base(AU)

Ecstasy pill testing: harm minimization gone too far?

Harm reduction has become the focus of public health initiatives and therapeutic intervention in the management of dependent drug use over the last 20 years. The last decade has seen such approaches being extended to recreational drug use. Most harm reduction initiatives have aimed to inform users about risks and ways of minimizing risk. The concept of providing illicit drug users with quality assessment of their chosen drug is one possible harm reduction intervention that until recently has received little attention. In response to well-publicized 'ecstasy'-related deaths organizations in some European countries and the United States have chosen to provide a 'pill testing service' for users. There are two broad categories of pill testing offered. Simple colour reagent test kits (Marquis Reagent and colour charts) form the most widely used on-site pill testing method. Less frequently, but more accurately, laboratory personnel with access to sophisticated chromatographic equipment (high performance liquid chromatography (HPLC) or gas chromatography-mass spectrometry (GC-MS)) may provide analysis of a pill. Pill testing kits have been advocated as a 'tool to protect yourself against the polluted XTC market'. We refute this line of reasoning. Of the different tests only techniques such as GC-MS can identify satisfactorily the psychoactive constituents present in ecstasy pills. Colour tests based on an interpretation of a colour response in the presence of a drug are, at best, subjective. Pill testing of any description does not guarantee safety, or protect the consumer against individual responses to pills. At best it gives an artificial 'shine of safety' to a group of diverse drugs that remain both illicit and potentially harmful. Other simpler harm reduction mechanisms are likely to be more effective.