Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine

Abstract

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6-11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety.

Keywords: 3D-printed tablets; SNEDDS; curcumin oil; glimepiride; personal medicine; rosuvastatin.

Figure 1

Rheograms of the prepared pastes (F1–F5) used in 3D-printing.

Figure 2

Images and SEM photographs for the surface and inner structure of SNEDDS-based (F1) and non-SNEDDS (F2) based 3DP tablets.

Figure 3

In vitro drug release of glimepiride and rosuvastatin from the prepared 3DP tablet formulations.

Figure 4

FT-IR spectra of glimepiride, rosuvastatin, and the prepared 3DP tablets.

Figure 5

X-ray diffraction patterns of glimepiride, rosuvastatin, and the prepared 3DP tablets.

Figure 6

Plasma level-time curves for glimepiride (A) and rosuvastatin (B) after oral administration of the 3DP and marketed tablets to Male Wistar rats (n = 6). Note: * Indicates significant difference, at p < 0.05, between groups.