title: Effect of molecular weight and glass transition on relaxation and release behaviour of poly(DL-lactic acid) tablets.
abstract: Different molecular weight grades of poly(DL-lactic acid) were applied as release controlling excipients in tablets for oral drug administration. The role of molecular weight and glass transition in the mechanism of water-induced volume expansion and drug release of PDLA tablets was investigated. Modulated differential scanning calorimetry (MDSC) was used to determine the glass transition temperature of both dry and hydrated PDLA samples. The absorption rate and total amounts of sorbed water by the polymer were determined by dynamic vapour sorption (DVS). Expansion behaviour of PDLA tablets was measured using thermal mechanical analysis (TMA). At 95% relative humidity all molecular weight grades of PDLA sorbed 1.1-1.3% w/w water, as was determined with DVS. MDSC showed glass transition temperature reductions of 10-11 degrees C for all molecular weight grades of PDLA in water. Volume expansion studies using TMA showed that the molecular relaxation time and equilibrium porosity of the tablets increased with molecular weight. The mean relaxation time increased exponentially with the temperature interval T(g)-T. The onset temperature of shape recovery of hydrated tablets was approximately 8 degrees C lower than for dry samples. Drug release was only slightly affected by molecular weight. It is concluded that volume expansion of compressed PDLA tablets is related to the glass transition behaviour, originates from water-induced and thermally stimulated shape memory behaviour and is therefore highly dependent on the molecular weight of PDLA.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands. mail@polyganics.com
authors.forename: R
authors.initials: R
authors.lastname: Steendam
authors.forename: M J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.forename: W E
authors.initials: WE
authors.lastname: Hennink
authors.forename: H W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: C F
authors.initials: CF
authors.lastname: Lerk
mesh_terms: D019344:Lactic Acid / Q000737:chemistry*; D008970:Molecular Weight; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D013607:Tablets; D013816:Thermodynamics; D014783:Viscosity
chemical_list: D011091:Polyesters; D011108:Polymers; D013607:Tablets; D019344:Lactic Acid; C033616:poly(lactide)