Printing Technologies for Personalization of Dosage Forms: A study in Pharmaceutical Sciences

Along with the recognized advantages of personalized medicine, a demand for new manufacturing technologies that allow for production of such products has emerged. Conventional pharmaceutical manufacturing techniques that have been used for production of dosage forms based on the ‘one-size-fits-all’ concept are not always suitable for manufacturing personalized dosage forms due to the lack of flexibility. Printing technologies have been explored for this purpose as their precise and flexible nature allows for on-demand printing of a limitless number of product designs with various personalization features, e.g., patient-tailored drug content, drug release profile, and customized functionality.

In this thesis, three different printing technologies, i.e., fused deposition modeling (FDM), semisolid extrusion 3D printing (EXT), and inkjet printing (IJP), were used to prepare personalized solid dosage forms. Although all are printing techniques they require vastly different properties of the starting materials, involving solid, semisolid, and liquid states of matter. The starting materials prepared in this thesis were: drug-loaded filaments for FDM, drugloaded viscous dispersion for EXT, and drug-loaded ink solutions, as well as drug-free substrates for IJP. In the first study, FDM was utilized to print oral tablets with a personalized dose and tailored drug release of the model active pharmaceutical ingredient (API) isoniazid. This was achieved by modifying the digital design of tablets to be printed enabling printing of various-sized tablets with two different internal infill levels. In the second study, EXT and IJP were successfully used for production of orodispersible films (ODFs) containing 0.1-2 mg warfarin sodium (henceforward called warfarin). Regardless of the technique used to print warfarin, the desired dose was achieved by depositing the drug-containing feedstock material in a single layer. The printed ODFs were shown to have properties on par and even superior in some aspects compared to the oral powders in unit dose sachets (OPSs) compounded at hospital pharmacies today. The ODFs, moreover, offer ease of administration to pediatrics without the need for water. In the third study, IJP was used to prepare personalized data-enriched edible pharmaceuticals (DEEP) containing two cannabinoids. The cannabinoid-containing ink was deposited on a porous solid foam (substrate) in an information-rich pattern (IRP), enabling simultaneous incorporation of information and APIs (cannabinoids) in a single IRP. The dose was tailored by imprinting the solid foam with 1-10 layers of the drug-containing ink. IRPs offer the possibility to incorporate personalized information e.g., for the patient, caregiver, nurse as well as enable traceability and identification of solid dosage forms on a single dosage unit level. This could e.g., be used for improved treatment outcomes, preventing falsified medicines from entering the supply chain, preventing medication errors, or avoiding drug abuse.

This thesis gives an overview of different printing technologies used in the pharmaceutical field and contributes to the understanding of critical parameters for fabrication of personalized solid oral dosage forms. Moreover, it provides insight into the requirements and possible limitations of the different printing technologies that need to be considered along with the printed API(s) and the desired properties of the final solid oral dosage form. EXT is a versatile method that enables production of both low- and high-dose dosage forms at room temperature. However, EXT typically requires postprocessing steps such as drying or curing which adds to the manufacturing time and may cause deformation of the printed solid dosage form. IJP has the benefit of allowing easy incorporation of personalized IRPs on a single dosage unit, as well as the possibility to accurately prepare low-dose solid dosage forms. IJP is typically limited to fabrication of low-dose solid dosage forms as the technique is based on deposition of droplets in the picoliter range. Preparation of high doses by means of IJP would require a large volume of ink to be absorbed into the substrate. FDM has the strength in enabling production of complex inner structures, which e.g., can be used for tailoring of the drug release. One of the recognized drawbacks of the technology is the need for intermediate filaments used as feedstock material. Preparation of printable filaments with a high drug load has been proven challenging.