title: Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids.
abstract: A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.
authors.affiliation: Department of Chemistry, Division of Physical Chemistry, Lund University, Lund, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Knöös
authors.affiliation: Teknologisk Institut, Taastrup, Denmark.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Svensson
authors.affiliation: CR Competence AB, Lund, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ulvenlund
authors.affiliation: Department of food technology engineering and nutrition, Lund University, Lund, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Wahlgren
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D001826:Body Fluids; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D007422:Intestines; D012212:Rheology; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013501:Surface-Active Agents; C006903:carbopol 940