3D printing of lipid-based formulations into personalized solid oral dosage forms

Abstract: The pharmaceutical development process starts with patient populations and their unmet therapeutic needs. Traditional pharmaceutical manufacturing of solid oral dosage forms is based on the strategy of one-size-fits-all. This is problematic, especially for patient populations with high patient-to-patient variability, as in pediatrics. Historically, pharmaceutical development has focused on the adult population, neglecting the therapeutic needs unique to children. As a result, there is a lack of age-appropriate formulations—available in acceptable dosage forms and suitable dosage strengths—for safe and efficient drug therapies for children. To address this, additive manufacturing, more commonly known as three-dimensional (3D) printing, has emerged as a flexible manufacturing platform for production of dosage forms based on patient needs. Interest in 3D printing for pharmaceutical production has grown rapidly; however, to date the research has mainly focused on water-soluble drugs not in need of more advanced drug delivery systems to enable oral absorption. The overall aim of this thesis was therefore to develop lipid-based drug delivery strategies for poorly soluble drugs to be 3D printed into personalized solid oral dosage forms. In the first part, an observational study was performed at a pediatric oncology ward, together with analysis of the age-appropriateness of the oral medications. Administration through enteral feeding tubes was identified as the main reason for manipulation of the solid dosage forms. Furthermore, active pharmaceutical ingredients requiring age-appropriate, personalized dosage forms were identified. In the next part, emulsion gels from emulsified lipid-based formulations stabilized by surfactants (surfactant-stabilized emulsion gels) or solid particles (Pickering emulsion gel) were developed to incorporate a poorly water-soluble model compound. The rheological properties of the emulsion gels were investigated. The developed emulsion gels were successfully 3D printed into solid oral dosage forms by semi-solid extrusion (SSE). In the last part, central quality control attributes, including both the printable formulation and the 3D-printed tablets, were studied in the 3D-printing method developed for one of the emulsion gels. The SSE 3D-printed tablets complied with standardized uniformity tests for both mass and drug content and demonstrated high dose accuracy and short-term storage stability. To conclude, a method for SSE 3D printing of emulsion gels into lipid tablets was developed with promising potential for personalized dosing of lipophilic drugs in a clinical setting.