Modeling drug release from a layered double hydroxide–ibuprofen complex

Drug delivery by layered double hydroxides (LDHs) is extensively studied due to the capacity of these solids to preserve the active agent and to modify its release rate and bioavailability. In this work, an ibuprofen–LDH complex was synthesized with high drug content (54% w/w), incorporated both in the interlayer and on the surface. The mechanisms involved in the ibuprofen release process were studied as a function of the anion type (chloride, acetate, and phosphate) and concentration, and the pH of the release media. The experimental conditions selected were based on the composition of pharmaceutically relevant fluids such as gastric, intestinal and lysosomal simulated media. Three release mechanisms accounted for the rate and extent of the drug release: ion exchange (highly dependent on the anions), desorption and weathering (dependent on the pH). These mechanisms, together with the different solubility of the anionic and non-ionic ibuprofen species, also explained the release behavior for particulate solid and hydrogel formulations. Anion exchange determined ibuprofen release in intestinal medium (phosphate anions pH 6.8) whereas surface reactions mediated by solid weathering or drug solubility ruled the release in acid media (gastric fluid and lysosomal medium).

Ibuprofen (Ibu) release and proton uptake (ΓH) dependence on pH (right) and schematic representation of the main mechanisms in each pH range (left).Figure optionsDownload as PowerPoint slideHighlights
► High loading LDH–ibuprofen complex with drug on the surface and in the interlayer.
► Anion exchange, desorption and LDH weathering as drug release mechanism.
► Release rate dependent on the exchanging anion and pH.
► Anion diffusion or surface reactions as rate determining step.
► Increased ibuprofen apparent solubility, dependent on the pH and LDH weathering rate.