ABSTRACT
Abstract Insomnia is becoming increasingly prevalent in the world general population. Therapies used by patients include over-the-counter therapies, herbal and dietary supplements, and pharmacological or nonpharmacological treatments. Among these, zolpidem is a pharmacological treatment popularly used for insomnia. Zolpidem is well tolerated and especially efficacious for initiation of sleep, and therefore is effective for the treatment of sleep-onset insomnia. The purpose of the present study was to design and evaluate zolpidem nanoparticle-impregnated buccal films to prolong the duration of its action. Zolpidem nanospheres were prepared by double emulsion solvent evaporation and then loaded into buccoadhesive films (Z1-Z4) comprised of different concentrations of HPMC K100, Eudragit® RL 100, and carbopol 974P. The prepared films were characterized for physicomechanical properties, mucoadhesion, percent hydration, in vitro drug release, ex vivo permeation, and in vivo studies. In vitro drug release was found to depend upon film composition. Ex vivo studies showed that film Z4 had the highest flux. In vivo studies revealed that administration of zolpidem nanosphere-impregnated film enhanced absorption of the drug (p < 0.0001), with a higher peak plasma concentration (52.54 ± 8.22 ng/mL) and area under the curve from time 0 to α (236.00 ± 39.51 ng.h/mL) than oral administration. The increase in time taken to reach the maximum drug concentration (1.5 h) further signifies the potential of these films to provide prolonged drug release. Given these promising results, we concluded that these buccal films could be an alternative route for effective zolpidem delivery.
Subject(s)
Animals , Male , Pyridines/administration & dosage , Acrylic Resins/administration & dosage , Drug Delivery Systems/methods , Nanospheres/administration & dosage , Hypnotics and Sedatives/administration & dosage , Pyridines/pharmacokinetics , Rabbits , Reference Values , Time Factors , Acrylic Resins/pharmacokinetics , Water/chemistry , Biological Availability , Microscopy, Electron, Scanning , Administration, Oral , Reproducibility of Results , Treatment Outcome , Zolpidem , Hypnotics and Sedatives/pharmacokinetics , Sleep Initiation and Maintenance Disorders/drug therapyABSTRACT
El presente trabajo se realizó con el propósito de comprobar la conveniencia de la aplicación de resinas acrílicas en medio acuoso para recubrir tabletas, empleándose 2 tipos de tabletas, oblangos y ovaladas a los que se aplicaron 2 tipos de resinas acrílicas, una para cubierta entérica y otra para liberación a nivel del estómago ensayándose diversos espesores de película y cantidades diferentes de materiales hidrófilos de modo que se pudiera definir un menor tiempo de liberación acorde al pH del tracto gastrointestinal. La aplicación de las resinas acrílicas se efectuó empleando un bombo grageador piloto, al cual se adaptó un ventilador de aire frio, una secadora y una pistola de aire comprimido, con una sola tobesa manteniéndose, para la pulverización de las resinas, condiciones definidas de ángulo y velocidad de rodamiento de las tabletas, el ángulo de inclinación de la aguja inyectora y la temperatura de aire de secado. Las tabletas ovaladas fueron más fáciles de recubrir en tanto que los oblangas demandaron de una mayor velocidad de rodamiento para evitar que se pegasen entre si.