Release kinetics from LDH-drug hybrids: Effect of layers stacking and drug solubility and polarity

•High drug loading, even exceeding anion exchange capacity, due to lateral interactions.•Compact disposition of LDH-D hybrids when compressed, slowed surface reactions and diffusion.•Faster release by anion exchange in neutral media, rate dependent on the apolar tail of the drug.•Slow matrix weathering in acidic media, release rate and mechanism dependent on drug solubility. This work highlights the effect of drug solubility and polarity and solid layer stacking on the release rate and mechanism of layered double hydroxides-drug (LDH-D) hybrids. With such a purpose, LDH-D hybrids containing three structural related non-steroidal anti-inflammatory drugs (ibuprofen, naproxen or ketoprofen) were synthesized by a simple co-precipitation method. LDH matrixes exhibited a high drug loading capacity, even exceeding the anion exchange capacity of the solid especially with the more apolar drugs. The structure and interfacial properties of the particulate LDH-D hybrids were also dependent on the polarity of the loaded drug. Finally, the release mechanisms in neutral and acidic media were studied with compressed LDH-D hybrids. The hybrids compression leaded to highly stacked platelets that caused a slower and steadier drug release rate than particulate LDH-D hybrids in all cases. In neutral medium, the drugs were exclusively released by anion exchange with HPO42− ions and the release rate was determined by the drug polarity. In acidic medium, weathering was the main release mechanism. However, additional processes (anion exchange, drug solubilization) were concurrent in the latter media, the overall mechanism and release rate being dependent on the drug solubility.