title: New co-processed MCC-based excipient for fast release of low solubility drugs from pellets prepared by extrusion-spheronization.
abstract: In this study, a new co-processed excipient composed of microcrystalline cellulose (MCC), sorbitol, chitosan and Eudragit® E, easily obtained by wet massing, to increase the dissolution rate of active ingredients of low water solubility from pellets prepared by extrusion-spheronization is evaluated. Indomethacin, nifedipine, furosemide, ibuprofen, prednisolone and hydrochlorothiazide are used as model drugs of different solubility. All pellet formulations evaluated showed adequate morphological, flow and mechanical properties. Pellets prepared with the co-processed excipient show a higher drug dissolution rate than those prepared with MCC and even higher than the pure drug powder. The fast drug dissolution and the complete disintegration (<3 min) of the pellets can be explained by the great porosity of the formulations, the high solubility of the sorbitol, the disintegrant capacity of the chitosan and the distribution of the Eudragit® E polymer particles in-between the other components of the co-processed mixture. In conclusion, this new co-processed excipient is very suitable to increase the dissolution rate of poorly soluble drugs from pellets prepared by extrusion-spheronization. Moreover, the drug release rate can be estimated from the Ln of the drug solubility in acidic medium.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela , Santiago de Compostela , Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Goyanes
authors.forename: Ramón
authors.initials: R
authors.lastname: Martínez-Pacheco
mesh_terms: D002482:Cellulose / Q000138:chemical synthesis* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D048271:Chitosan / Q000138:chemical synthesis / Q000378:metabolism; D004343:Drug Implants / Q000138:chemical synthesis* / Q000378:metabolism; D005079:Excipients / Q000138:chemical synthesis* / Q000378:metabolism; D012995:Solubility; D013012:Sorbitol / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D004343:Drug Implants; D005079:Excipients; D013012:Sorbitol; D002482:Cellulose; D048271:Chitosan; C109691:microcrystalline cellulose
keywords: Chitosan; Eudragit® E; co-processed excipient; microcrystalline cellulose; pellet; sorbitol