title: An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose.
abstract: An innovative matrix, produced by thermal treatment on direct compression (DC) tablets containing polycarbophil (POL) and ethylcellulose (EC), identified as matrix forming polymers, and able to control the release of diltiazem hydrochloride, was developed. At pH 7.2, 72 ± 1.2% (w/w) of drug loaded was released in 25 h, mostly at constant rate. This swellable and unerodible matrix controls drug release by an anomalous transport mechanism. The modifications induced by the thermal treatment are irreversible and can be used to control and characterize the matrix. A 3-component constrained mixture design allowed the investigation of the experimental domain in which the matrix forms and the computation of a mathematical model that can be used to optimize the formulation properties. The release rate can be modulated (0.032-0.064% drug released/min) through the choice of suitable treatment conditions and tablet composition. The maximum amount of diltiazem hydrochloride released by zero-order kinetics, at the lowest release rate, occurs for POL:EC ratio in the range of 1:1-2:3 with 20-30% of diluent. The tablets are able to load up to 50% (w/w) of diltiazem hydrochloride without losing their properties. A stability study performed on a selected formulation containing DTZ showed stability for at least 2.7 years at RT conditions.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Via Brigata Salerno, 13, 16147 Genova, Italy. Electronic address: caviglioli@difar.unige.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Caviglioli
authors.forename: Sara
authors.initials: S
authors.lastname: Baldassari
authors.forename: Paola
authors.initials: P
authors.lastname: Cirrincione
authors.forename: Eleonora
authors.initials: E
authors.lastname: Russo
authors.forename: Brunella
authors.initials: B
authors.lastname: Parodi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gatti
authors.forename: Giuliana
authors.initials: G
authors.lastname: Drava
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004110:Diltiazem / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D006358:Hot Temperature; D011108:Polymers / Q000737:chemistry; D011312:Pressure; D013607:Tablets / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; C013517:ethyl cellulose; C030312:calcium polycarbophil; D002482:Cellulose; D004110:Diltiazem
keywords: Controlled release; DC; DC tablet; DF; DTZ; EC; Ethylcellulose; HME; LA; ML; Matrix tablets; MicroceLac(®) 100; NT; POL; Polycarbophil; T; Thermal treatment; dicalcium phosphate anhydrous; diltiazem hydrochloride; direct compression; ethylcellulose; hot melt extrusion; lactose anhydrous; polycarbophil; treated; untreated