The focus of this research was to understand the effects of formulation and processing variables on the very-rapidly dissolving printlets of isoniazid (INH) manufactured by the selective laser sintering (SLS) three-dimensional (3D) printing method, and to characterize their physicochemical properties, stability, and pharmacokinetics. Fifteen printlet formulations were manufactured by varying the laser scanning speed (400-500 mm/s, X1), surface temperature (100-110 °C, X2), and croscarmellose sodium (CCS, %, X3), and the responses measured were weight (Y1), hardness (Y2), disintegration time (DT, Y3), and dissolution (Y4). Laser scanning was the most important processing factor affecting the responses. DT was very rapid (≥3 s), and dissolution (>99%) was completed within 3 min. The root-mean-square error in the studied responses was low and analysis of variance (ANOVA) was statistically significant (p < 0.05). X-ray micro-computed tomography (micro-CT) images showed very porous structures with 24.6-34.4% porosity. X-ray powder diffraction and differential scanning calorimetry data indicated partial conversion of the crystalline drug into an amorphous form. The printlets were stable at 40 °C/75% RH with no significant changes in assay and dissolution. Pharmacokinetic profiles of the printlets and compressed tablets were superimposable. In conclusion, the rapidly dissolving printlets of the INH were stable, and oral bioavailability was similar to that of compositionally identical compressed tablets.
Keywords: isoniazid; pharmacokinetics; printlets; recyclability; selective laser sintering; stability.