Modified Release 3D-Printed Capsules Containing a Ketoprofen Self-Nanoemulsifying System for Personalized Medical Application.

This study explores the realm of personalized medicine by investigating the utilization of 3D-printed dosage forms, specifically focusing on patient-specific enteric capsules designed for the modified release of ketoprofen, serving as a model drug. The research investigates two distinct scenarios: the modification of drug release from 3D-printed capsules crafted from hydroxypropyl methylcellulose phthalate:polyethylene glycol (HPMCP:PEG) and poly(vinyl alcohol) (PVA), tailored for pH sensitivity and delayed release modes, respectively. Additionally, a novel ketoprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) based on pomegranate seed oil (PSO) was developed, characterized, and employed as a fill material for the capsules. Through the preparation and characterization of the HPMCP:PEG based filament via the hot-melt extrusion method, the study thoroughly investigated its thermal and mechanical properties. Notably, the in vitro drug release analysis unveiled the intricate interplay between ketoprofen release, polymer type, and capsule thickness. Furthermore, the incorporation of ketoprofen into the SNEDDS exhibited an enhancement in its in vitro cylooxygenase-2 (COX-2) inhibitory activity. These findings collectively underscore the potential of 3D printing in shaping tailored drug delivery systems, thereby contributing significantly to the advancement of personalized medicine.

Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach.

Extrusion-based 3D-printing is an easy-to-use, cheap manufacturing technique that could be used to produce tailored precision medicines. The technique has an almost unlimited versatility since a multitude of print parameters can easily be adapted. Unfortunately, little is known of the effect of these print parameters on the critical quality attributes of the resulting printlets. In this study, practical guidelines and means to adapt certain parameters in order to achieve the desired outcome (e.g., acceptable visual quality and flexible dosing) are stipulated for medical 3D-printing using a design-of-experiments approach. The current study aims at elucidating the effect of five print parameters (infill, overlap, number of shells, layer height and layer pattern) on the mechanical properties, dimensions, weight, porosity and dissolution characteristics of a fixed-size caplet consisting of Eudragit EPO (69.3%), Polyox WSR N10 (29.7%) and zolpidem hemitartrate (1%). In terms of the mechanical properties, 3D-printed caplets possessed anisotropy where the vertical compression strength and Brinell hardness exceeded the diametral strength. In general, all 3D-printed caplets possessed acceptable mechanical strength except for a small region of the knowledge space. Dimensional analysis revealed small, statistical significant differences between different runs, although the clinical relevance of this variation is likely negligible. The weight or dose of a caplet can be varied mainly using the infill and overlap and, to a lesser extent, via the layer height and number of shells. The impact on porosity was complicated as this was influenced by many factors and their interactions. Infill was the only statistically relevant factor influencing the dissolution rate of the current formulation. This study unravels the importance of the print parameter overlap, which is a regularly neglected parameter. We also discovered that small dose variations while maintaining the same dissolution profile were possible via modifying the overlap or number of shells. However, large dose variations without affecting the dissolution behaviour could only be accomplished by size modifications of the printlet.