Zaltoprofen-layered double hydroxide hybrids to enhance zaltoprofen solubility and dissolution rate

Abstract

The zaltoprofen-LDH hybrid was successfully synthesized by coprecipitation method, and its dissolution profile and solubility in different fluids, that simulate the gastro-intestinal environment, were investigated. The zaltoprofen-LDH hybrid stoichiometry was determined by EDS and TGA, and the Zn0.70Al0.30(OH)2Z0.30·0.76H2O chemical formula was obtained, which well compares to the Zn/Al molar ratio of the pristine LDH (nitrate-LDH hybrid: Zn0.73Al0.27(OH)2(NO3)0.27·0.44H2O), synthesized to prepare the zaltoprofen-LDH physical mixture for the dissolution tests. The XRPD results confirmed the successful insertion of the zaltoprofen in the interlayer space of the LDH structure: the 003 reflection, detected at d-value of 8.7 Å in the pristine LDH, was observed at d-value of 21.8 Å, and the drug occupied a gallery of about 17 Å. Based on the zaltoprofen size (9.9 × 4.9 Å), a drug arrangement in which the molecules form a monolayer of partially superimposed drug anions into the brucite-like layer is suggested. The DSC peak due to the melting process of the pure zaltoprofen was not observed in the zaltoprofen-LDH hybrid, thus indicating the loss of the long-range structural order in the active principle. FT-IR spectroscopy confirmed that the zaltoprofen entered the host structure in the anionic form (COO−). Deep insights in the drug-LDH interaction were obtained by 13C and 27Al solid state NMR: the zaltoprofen molecules strongly interacted with the LDH layers involving the COO- and the OH moieties respectively, while the packing of the drug molecules in the layers was comparable to the conformation of the pure zaltoprofen crystals. The zaltoprofen anion insertion caused local structural changes within the host crystal structure. The solubility and dissolution tests, performed on the synthesized hybrid and compared to the pure zaltoprofen and zaltoprofen-LDH physical mixture, demonstrated enhanced solubility and dissolution rate of the drug in the hybrid system.