Development of 3D-Printed, Liquisolid and Directly Compressed Glimepiride Tablets, Loaded with Black Seed Oil Self-Nanoemulsifying Drug Delivery System: In Vitro and In Vivo Characterization.

ABSTRACT

Glimepiride is characterized by an inconsistent dissolution and absorption profile due to its limited aqueous solubility. The aim of this study was to develop glimepiride tablets using three different manufacturing techniques, as well as to study their quality attributes and pharmacokinetics behavior. Black seed oil based self-nanoemulsifying drug delivery system (SNEDDS) formulation was developed and characterized. Glimepiride liquisolid and directly compressed tablets were prepared and their pre-compression and post-compression characteristics were evaluated. Semi-solid pastes loaded with SNEDDS were prepared and used to develop three-dimensional printing tablets utilizing the extrusion technique. In vivo comparative pharmacokinetics study was conducted on Male Wistar rats using a single dose one-period parallel design. The developed SNEDDS formulation showed a particle size of 45.607 ± 4.404 nm, and a glimepiride solubility of 25.002 ± 0.273 mg/mL. All the studied tablet formulations showed acceptable pre-compression and post-compression characteristics and a difference in their in vitro drug release behavior. The surface of the liquisolid and directly compressed tablets was smooth and non-porous, while the three-dimensional printing tablets showed a few porous surfaces. The inner structure of the liquisolid tablets showed some cracks and voids between the incorporated tablet ingredients while that of the three-dimensional printing tablets displayed some tortuosity and a gel porous-like structure. Most of the computed pharmacokinetic parameters improved with the liquisolid and three-dimensional printed tablets. The relative bioavailabilities of the three-dimensional printed and liquisolid tablets compared to commercial product were 121.68% and 113.86%, respectively. Therefore, the liquisolid and three-dimensional printed tablets are promising techniques for modifying glimepiride release and improving in vivo performance but more clinical investigations are required.