title: In vitro release testing of matrices based on starch-methyl methacrylate copolymers: effect of tablet crushing force, dissolution medium pH and stirring rate.
abstract: Direct-compressed matrix tablets were obtained from a variety of potato starch-methyl methacrylate copolymers(1) as sustained-release agents, using anhydrous theophylline as a model drug. The aim of this work was to investigate the influence of the copolymer type, the tablet crushing force and dissolution variables such as the pH of the dissolution medium and the agitation intensity on the in vitro drug release behaviour of such matrices. Commercial sustained-release theophylline products (Theo-Dur(®) 100mg, Theolair(®) 175 mg) were used as standards. Test formulations were compacted into tablets at three different crushing force ranges (70-80, 90-100 and 110-120 N) to examine the effect of this factor on the porous network and drug release kinetics. In vitro release experiments were conducted in a pH-changing medium (1.2-7.5) with basket rotation speeds in the range 25-100 r.p.m. to simulate the physiological conditions of the gastrointestinal tract. The release rate of theophylline was practically not affected by pH in the case of Theo-Dur(®) and HSMMA matrices. In contrast, Theolair(®) and CSMMA tablets demonstrated a biphasic drug release pattern, which appeared to be sensitive to the pH of the dissolution medium. An increase in the crushing force of the copolymer matrices was accompanied by a reduction of the matrix porosity, although the porous network depends markedly on the type of copolymer, having a strong influence on the drug release kinetics. Mathematical modelling of release data shows a Fickian diffusion or anomalous transport mechanism. Based on the similarity factor f2, FD-HSMMA, OD-CSMMA and FD-CSMMA at 90-100 N were selected for agitation studies. In general, all formulations showed an agitation speed-dependent release, with Theo-Dur(®) and FD-CSMMA matrices being the less susceptible to this factor.
authors: Dpto. Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González n° 2, 41012 Sevilla, Spain. Electronic address: cferrero@us.es.
authors: C
authors: C
authors: Ferrero
authors: Dpto. Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González n° 2, 41012 Sevilla, Spain.
authors: M R
authors: MR
authors: Jiménez-Castellanos
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D020366:Methylmethacrylate / Q000737:chemistry*; D008962:Models, Theoretical; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D011198:Solanum tuberosum / Q000737:chemistry; D012995:Solubility; D013213:Starch / Q000737:chemistry*; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; D020366:Methylmethacrylate; D013213:Starch; D013806:Theophylline
keywords: Drug release kinetics; Potato starch–methyl methacrylate copolymers; Stirring rate; Sustained-release matrix tablet; Tablet crushing force; pH-changing medium