Development of UV-cured captopril-loaded ink for pharmaceutical 3D printing by custom-built SSE extruder.

Abstract

It is widely acknowledged that conventional dosage forms are frequently not adequately customized to meet the specific clinical requirements of individual patients, what induces the need to process existing dosage forms to improve comfort and patient compliance. This phenomenon is especially evident in pediatric and geriatric populations, where there is a shortage of adequate doses of medication or where a difficulty is reported in their administration. Personalized soft gel-based dosage forms offer a viable solution to the problems associated with the administration of solid forms, especially in special needs populations. One of the most promising technologies that has the potential to facilitate personalization and the production of soft dosage forms is three-dimensional printing (3DP) using the semi-solid extrusion (SSE) method. This method allows the processing of low melting point materials and colloidal materials, e.g. gels and pastes. In this study, a light-curable gel (ink) was designed using a polyethylene glycol diacrylate (PEGDA) as a base polymer. Riboflavin and L-arginine were used as photoinitiators, demonstrating that it is possible to fabricate UV-cured gels without the need for potentially toxic ingredients such as triethylamine, or TPO/DPPO commonly used in this type of formulations. The model drug incorporated into the ink was captopril, which primary indication is the treatment of hypertension and heart failure. The possibility of using an individualized approach to its dosing could reduce the risk of adverse effects, particularly in elderly or pediatric patients. For the 3D printing process of soft dosage forms SSE extruder designed by the authors has been used. Demonstrative version of extruder can be installed in commercial FDM (Fused Deposition Modeling) printers which enables the execution of a considerable number of experiments using a variety of gels under controlled laboratory conditions, without the need for a significant financial investment. In a final experiment, a series of donut-shaped tablets were printed from the designed ink, which exhibited immediate drug release (over 80% within 30 min). Additionally, in this study an interesting phenomenon observed was improvement in polymerization of API-incorporated ink, what based on NMR spectra analysis may be explained by beneficial influence of captopril structure itself and its thiol group on cross-linking process progress. Summarizing, an ink composition formulated in the presented project that contains non-toxic photoinitiators and co-initiators can be utilized in an innovative self-assemble SSE extruder compatible with FDM commercial 3D printer, with optional UV-curing system.