title: Mechanical properties of excipients do not affect polymer matrix formation.
abstract: Coalescence of polymer particles has been identified as a crucial step in film formation on tablets, pellets and granules. Though the significance of thermal treatment on matrix dosage forms is well established the process of coalescence in matrix formation and the forces driving it remain unexplored. The aim of this study was to investigate whether stresses in tablets, caused by deformation of excipient during compression, provide a driving force for polymer matrix formation. Polymer matrix tablets containing Eudragit-RLPO, a pH independent and permeable polymer at two levels 10 and 40% (w/w) were prepared by direct compression. Either lactose monohydrate (brittle) or mannitol (plastic) was used as a diluent at 80 or 50% (w/w) and indomethacin, a model drug was present at 10% (w/w). Tablets from each formulation type were prepared at two compression pressures either 221 MPa (above the yield pressure of both excipients) or 74 MPa (below the yield pressure of both excipients). Tablets from each formulation type compressed at the two compression pressures were thermally treated at 40 degrees C (below Tg) or 70 degrees C (above Tg) for 24 h. The rotating basket (100 rpm) method was used for the release studies conducted at 37 degrees C in 900 ml phosphate buffer (0.2 M) pH 7.2 as the dissolution medium. Morphological characteristics of the tablets were observed by scanning electron microscopy. Differences in tablet structure due to the formulation and processing variables were further evaluated by disintegration and tensile strength testing. Data from this factorial study were analysed by analysis of variance. Excipient mechanical properties determine matrix properties only at low polymer level independent of curing temperature and at high polymer level cured at 40 degrees C only. Though lactose and mannitol have different mechanical properties and therefore different deformation behaviors, this did not influence the properties of tablets containing 40% (w/w) polymer cured at 70 degrees C, suggesting stresses in these tablets are not a significant driving force for matrix formation.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, Otago 9054, New Zealand. chali858@student.otago.ac.nz
authors.forename: Lipika
authors.initials: L
authors.lastname: Chatterjee
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Ian G
authors.initials: IG
authors.lastname: Tucker
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D019563:Mechanics; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*
chemical_list: D005079:Excipients; D011108:Polymers