Biocompatible encapsulated drug delivery materials are highly desired as they provide for controlled release of bioactive agents, thereby improving the effectiveness of medical treatments. Some of the key properties of better materials for drug delivery include high adsorptive capacity, which can be realized by smectites, a family of clay minerals. Here the influence of pH on encapsulation of the bioactive molecule ciprofloxacin (CIPRO), an antibiotic, by fluorohectorite (FHt), a synthetic smectite, was investigated. Aspects of the clay structure itself were also investigated. By means of X-ray powder diffraction (XRD), thermogravimetric analysis coupled to Fourier transform infrared spectroscopy (TGA/FTIR) and inelastic neutron scattering (INS), it is demonstrated that the capture of ciprofloxacin is more efficient at acidic pH. Geometric considerations based on the XRD results and mass calculations based on the TGA results provided evidence that at acidic pH, the CIPRO-FHt complex contained one CIPRO molecule per unit cell, while at neutral pH the CIPRO content was about half, despite having similar interlayer volume available. Finally it is shown that adsorption of CIPRO by FHt facilitated removal of residual water from the interlayer, providing additional evidence that intercalation is the main adsorptive mechanism at acidic pH. These results lead to a deeper understanding concerning the capture of amphoteric drug molecules by smectites, as well as concerning their molecular interactions, which may lead to more feasible application of clay minerals as a carrier for drug molecules.