Three-Dimensional Printing of Repaglinide Tablets: Effect of Perforations on Hypromellose-Based Drug Release

Purpose: Drug release from hypromellose-based tablets involves the formation of characteristic dry cores surrounded by outer gel layers in aqueous media. The aim of this study was to investigate the effect of perforation sizes on the dissolution of repaglinide from three-dimensionally (3D) printed tablets with two viscosity grades of hypromellose as rate-controlling polymer. Methods: Printing pastes of appropriate consistency were developed and fed into a bioplotter cartridge to extrude strands/filaments. Tablets were printed in a crisscross pattern with 1.0, 1.3, and 1.6 mm of inter-strand distances. Printed tablets were characterized and repaglinide dissolution data were evaluated mathematically. Results: Scanning electron microscopy images confirmed the sealing of the defect-free strands. Differential scanning calorimetry studies indicated potential interaction of ingredients above 150 °C which suggested that the formulation, printing, and drying of tablets should be performed at room temperature. All of the tablets possessed acceptable size, shape, and mechanical strength. Repaglinide dissolution data were evaluated by similarity factor (f2), dissolution efficiency, and two-way analysis of variance (ANOVA) which revealed that drug release rate and extent could be gradually increased by increasing the perforation sizes inside the tablets. Korsmeyer-Peppas modeling of dissolution data showed that the drug release rate approached zero-order kinetics and the release mechanism was Super Case II. This mechanism implies that an outer layer of HPMC gel limits the swelling of the characteristic HPMC tablet cores. Conclusion: The cores in HPMC tablets usually remain dry for long time in aqueous media. Higher perforation sizes enhanced repaglinide dissolution rate from such tablets. This led us to conclude that different perforation sizes in the tablets must have caused differences in the structural consistency of the core. Perforation sizes played the dominant role over HPMC viscosity grades in determining repaglinide release.