Pharmaceutical Salt Formation as a Strategy to Enhance In Situ Drug Loading into Apatite-Based Materials

Abstract Water-based loading is attractive for pharmaceutical and industrial applications and helps prevent damage to drug carriers; however, the poor aqueous solubility of many APIs, such as ciprofloxacin (CIP), limits their incorporation into these systems. To overcome these limitations, this work explores the use of a ciprofloxacin–dexketoprofen (CIP–DKT) pharmaceutical salt to improve API solubility and in situ loading into sensitive apatite platforms, including biomimetic apatite nanoparticles (Ap) and apatite-mineralized eggshell membranes (ApESM). Computational and solid-state characterization rationalized the improved aqueous solubility and drug loading observed with CIP–DKT. CIP showed higher affinity for the negatively charged apatite surface, whereas DKT displayed lower affinity and, due to its acidic nature, altered the synthesis pH, affecting apatite morphology and ESM mineralization. Interestingly, CIP–DKT enabled the simultaneous incorporation of CIP and DKT while preserving the biomimetic apatite morphology and the mineralization of the ESMs, likely due to the buffering effect of CIP. Final HPLC and antibacterial assays confirmed pH-dependent API release and sustained antibacterial activity against Escherichia coli, with improved diffusion from ApESM–CIP–DKT. Overall, these results demonstrate that pharmaceutical salt formation is an efficient strategy to enhance the incorporation of poorly soluble APIs into sensitive materials under water-based processing conditions.