Synthesis and characterization of ZnAl-NO3(-CO3) layered double hydroxide: A novel structure for intercalation and release of simvastatin

Recently, simvastatin (SIM) has been introduced as a stimulator for bone generation. Its controlled delivery rate is determinant for this purpose. In this work, layered double hydroxide (LDH) based drug delivery systems are introduced for SIM drug for the first time. It was loaded into a series of ZnAl-NO3(-CO3) LDHs using two different synthesis processes, namely the direct coprecipitation in the presence of SIM and the ion exchange of nitrate and carbonate containing LDHs in SIM solution. The structure, surface morphology, drug loading, thermostability, and chemical bonding were characterized, and the drug release profile and release kinetic of intercalated LDHs were studied. The characterization results revealed that the intercalation, surface bonding and release behavior of SIM are different for carbonate and nitrate LDHs and moreover depend on the synthesis process. X-ray photoelectron spectroscopy and differential scanning calorimetry studies revealed the stronger chemical bonds between SIM and interlayer surfaces of the nitrate LDHs than carbonate types. From an ion-exchange process, the loaded drug quantity into LDH was 7.9 and 2 wt% for NO3- and CO3-based LDHs, respectively, while was 16.2 and 5.5 wt% for coprecipitation process. The release behavior of SIM from intercalated compounds was well-described with modified Freundlich and Elovich models, and NO3-based LDH system showed sustained drug delivery compared to that of CO3-based LDH with relatively lower drug loading. The drug release rates of 84% and 93% were found for CO3-based LDH compared to that of 35% and 45% for NO3-based counterpart after 58 h. Taken together, the NO3-based system loaded with SIM drug could be considered as a potential drug delivery system for bone tissue repair applications.