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 ?, to 18.5-27 ?, 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.

Automated summary

Two novel biocompatible hydroxy double salts (HDS), MgZn-Cl and FeZn-Cl, were found to successfully intercalate diclofenac, ibuprofen, and valproate. Drug release studies showed that the solubility of the drug ions controls the fate of the HDS in an acidic environment, with valproate intercalates dissolving completely at pH 1.0 within two hours. The HDS were also found to be biocompatible and stable upon storage for 5 years in vitro.