Inkjet Printing of Drugs into Surface-Embedded Micro-Reservoirs for Drug-Releasing Implants: Influence of Solvent Properties on Deposition Behavior

Background: Micro-reservoirs in implant surfaces represent a promising drug carrier concept for drug delivery systems. For drug loading, inkjet printing enables highly precise droplet positioning. However, droplet drying influences drug crystallization from printed drug solution. This study investigates how evaporation-driven phenomena affect the precision and homogeneity of inkjet-based deposition of a crystallizing drug into exemplary micro-reservoirs. The aim is to guide the selection of suitable solvents and inkjet process parameters. Methods: Laser-drilled micro-reservoirs were fabricated as blind holes with entrance diameters of 100 µm and 400 µm in the surface of specimens of EN 1.4404 (equivalent to AISI 316L) stainless steel, a commonly used biomaterial. The reservoirs were loaded with two different drug solutions using piezoelectric drop-on-demand inkjet printing. Acetylsalicylic acid (ASA) was applied as a model drug representing crystallizing small-molecule drugs. Solvents with markedly different evaporation rates, ethanol (EtOH) as a representative high-volatility solvent and dimethyl sulfoxide (DMSO) as a representative low-volatility solvent, were selected. The number of jetted droplets per dispensing step was varied. Precision and homogeneity of the drug deposition were investigated using light and laser scanning microscopy. Results: Over the course of droplet drying, two phenomena, the coffee-ring effect and creeping, can impair drug deposition quality. The coffee-ring effect leads to inhomogeneous, ring-shaped drug deposits. Creeping is the evaporation-driven spreading of crystalline structures and reduces the precision of drug deposition. The EtOH-based ASA solution (c = 10 g/L) was intensely affected by both phenomena. Inhomogeneities could be partially compensated via tailoring the droplet count per dispensing step. The DMSO-based solution (c = 100 g/L) exhibited a more compact crystallization of ASA (requiring ~20% less volume in an exemplary experiment), no coffee-ring effect, and only minor creeping. Conclusions: The DMSO-based ASA solution enabled a more precise and homogeneous drug deposition than the EtOH-based solution under the investigated printing and crystallization conditions. EtOH-related limitations could be counteracted by controlling the number of jetted droplets per dispensing step.