Modified drug release system based on Sulindac and layered double hydroxide: An in vivo Raman investigation

In this study, the capability of a Layered Double Hydroxide (LDH) to promote the modified-release of Sulindac (Sul), a non-steroid anti-inflammatory drug, was followed by Raman spectroscopy through in vitro and in vivo assays. The drug and the LDH-Sul system were pressed into pellets and their dissolution under controlled conditions was monitored in vitro for 80h. For the in vivo assays, LDH-drug and LDH-Cl (with chloride in the interlayer space) pellets were implanted between the external and internal oblique muscles of Wistar rats. The pellets were removed after 7, 21, 28 and 35days from implantation and up to 21days there was an increase in the amount of intercalated carbonate ions as followed over time by Raman microscopy. The carbonate ions are from the extracellular fluid (conjunctive tissue) and replace the chloride ions between the LDH layers. The same kind of ion exchange was observed for LDH-Sulindac: ca. 50% of the drug was released in vivo after 21days, whereas in vitro the same amount of drug was delivered within 24h. The release kinetics was much slower in the in vivo assay due to a significantly smaller hydrodynamic interaction inside the muscle.