MALDI-TOF MS imaging of controlled release implants

Abstract MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) imaging is used to characterize novel lipid implants allowing for controlled drug delivery. Importantly, this innovative technique provides crucial information on the inner structure of the implants before and after exposure to the release medium and does not require the addition of marker substances. Implants were prepared by extrusion at room temperature. Thus, in contrast to hot-melt extruded systems, the risks of drug inactivation and solid state transformations of the lipid matrix former are reduced. Hydrogenated/hardened soybean oil and glyceryl tristearate were studied as lipids and propranolol hydrochloride and theophylline as drugs, exhibiting significantly different solubility in water. The implants were also characterized by optical microscopy, differential scanning calorimetry, water uptake and lipid erosion studies, mathematical modeling as well as in vitro drug release measurements. Importantly, broad spectra of drug release patterns with release periods ranging from a few days up to several months could easily be provided when varying the initial drug content and type of lipid, irrespective of the type of drug. The diameter of the implants can be as small as 1 mm, facilitating injection. MALDI-TOF MS imaging revealed homogeneous macroscopic drug distributions within the systems, but steep drug concentration gradients in radial and axial direction at the lower micrometer level, indicating drug- and lipid-rich domains. As the implants do not significantly swell, local irritation upon administration due to mechanical stress can be expected to be limited. Good agreement between experimentally measured and theoretically calculated drug release kinetics revealed that diffusional mass transport plays a major role for the control of drug release from this type of advanced drug delivery systems.