Biocompatible hydroxy double salts as delivery matrices for non-steroidal anti-inflammatory and anti-epileptic drugs

We recently reported the synthesis of two novel biocompatible hydroxy double salts (HDS), [Mg2Zn3(OH)8]Cl2·3.4H2O (MgZn-Cl) and [Fe2.4Zn2.6(OH)8]Cl2·2H2O (FeZn-Cl) (J. Mater. Chem. B 2016, 4, 5789) and showed them to be suitable for the loading and sustained release of naproxen. Here we build on these findings and report the intercalation, storage stability, biocompatibility and drug release properties of MgZn-Cl and FeZn-Cl loaded with diclofenac, ibuprofen, and valproate. All three active pharmaceutical ingredients could be successfully intercalated into both HDS by ion exchange. An increase in interlayer space from ca. 8 Å to 18.5–27 Å was observed after intercalation, consistent with the replacement of the initial chloride ion with the larger drug anions. Confirmation of successful intercalation was provided by IR spectroscopy, elemental microanalysis, and thermogravimetric analysis. 1H NMR revealed that the structural integrity of the drug ions is not affected by intercalation. Drug release studies were performed in conditions representative of the gastrointestinal tract, and showed that the solubility of the drug ions controls the fate of the HDS in an acidic environment. The valproate intercalates dissolved completely within two hours at pH 1.0, whereas the other drug-loaded HDS freed some of their drug payload in the acidic media and the rest at pH 6.8. The HDS are further found to be biocompatible in an in vitro cell viability test, and to remain stable upon storage for 5 years. [Display omitted] •Three drugs were intercalated into novel biocompatible hydroxyl double salts (HDS).•The HDS intercalates help prevent drug release at acidic pH.•Drug release is controlled by weathering (at low pH), and ion exchange (at pH ≥ 6.8).•Both pristine and loaded HDS are stable for at least five years' storage.•Both the pristine and loaded HDS are highly cytocompatible.