Abstract
In order to cope with the increasing number of multimorbid patients due to demographic changes, individualized polypill solutions must be developed. One promising tool is fused layer modeling (FLM) of dosage forms with patient-specific dose combinations and release individualization. As there are few approaches reported that systematically investigate the influence of high disperse active pharmaceutical ingredient (API) loads in filaments needed for FLM, this was the focus for the present study. Different filaments based on polyethylene oxide and hypromellose (HPMC) with different loads of theophylline as model API (up to 50 wt.%) were extruded with a twin-screw extruder and printed to dosage forms. Along the process chain, the following parameters were investigated: particle size and shape of theophylline; mechanical properties, microstructure, mass and content uniformity of filaments as well as dosage forms and the theophylline release from selected dosage forms. Especially for HPMC, increasing theophylline load enhanced the flexural strength of filaments whilst the FLM accuracy decreased inducing defects in microstructure. Theophylline load had no significant effect on the dissolution profile of HPMC-based dosage forms. Therefore, a thorough analysis of particle-induced effects is necessary to correlate mechanical properties of filaments, printability, and the dosage-and-release profile adjustment.
Highlights
Considering the demographic changes of society and the connected increase in multimorbid patients, new individualized therapies must be developed including the combination of highly dosed formulations in a single dosage form to improve patient compliance
As there are few approaches reported that systematically investigate the influence of high disperse active pharmaceutical ingredient (API) loads in filaments needed for fused layer modeling (FLM), this was the focus for the present study
Different filaments based on polyethylene oxide and hypromellose (HPMC) with different loads of theophylline as model API were extruded with a twin-screw extruder and printed to dosage forms
Summary
Considering the demographic changes of society and the connected increase in multimorbid patients, new individualized therapies must be developed including the combination of highly dosed formulations in a single dosage form to improve patient compliance. As a promising tool for the production of individualized solid dosage forms, additive manufacturing techniques have emerged in pharmaceutical research in the past two decades [1,2] With these techniques, three-dimensional objects are made without molds or tools by successive build-up of layers of source materials [3]. As there are only few different doses approved and only one dissolution profile is available, Spritam® does not utilize all advantages of additive manufacturing to produce individual dosage forms on demand. Another technique, selective laser sintering, was used to produce orally disintegrating [5] or modified-release tablets [6]. Fused layer modeling (FLM), where a polymer-API formulation is selectively deposited via a hot nozzle, represents extrusion-based technologies and is currently the fastest evolving technique in pharmaceutical research [1]
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