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. 2022 Aug 1;19(8):2937-2949.
doi: 10.1021/acs.molpharmaceut.2c00306. Epub 2022 Jun 1.

Very-Rapidly Dissolving Printlets of Isoniazid Manufactured by SLS 3D Printing: In Vitro and In Vivo Characterization

Tahir Khuroo  1 , Eman M Mohamed  1   2 , Sathish Dharani  1 , Canberk Kayalar  1 , Tanil Ozkan  3 , Mathew A Kuttolamadom  4 , Ziyaur Rahman  1 , Mansoor A Khan  1
Affiliations

Very-Rapidly Dissolving Printlets of Isoniazid Manufactured by SLS 3D Printing: In Vitro and In Vivo Characterization

Tahir Khuroo et al. Mol Pharm. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
(A) Hardness data and (B) actual and model predicted values of the hardness of the printlet formulations.
Figure 2.
Figure 2.
(A) Disintegration time data, and actual and model predicted values of the disintegration time of the printlets by (B) the USP disintegrator tester and (C) bottle shaking method.
Figure 3.
Figure 3.
(A) dissolution profiles, (B) actual and model predicted values of the dissolution in 2 min, and (C) dissolution profiles after storage of the printlet formulations at 40 °C/75% RH for a month.
Figure 4.
Figure 4.
(A) Scanning electron microscopy image of the INH, placebo, and printlets before and after exposure to the stability condition, and (B) micro-X-ray CT images of the printlets.
Figure 5.
Figure 5.
X-ray powder diffractograms of INH, placebo, and printlets.
Figure 6.
Figure 6.
X-ray powder diffractograms of the printlet formulation powder before and after the printing process.
Figure 7.
Figure 7.
Differential scanning calorimetry profiles of (A) INH, placebo, and printlets, and (B) stability of the exposed printlet formulations.
Figure 8.
Figure 8.
FTIR spectra of INH, placebo, and printlets before and after exposure to stability condition.
Figure 9.
Figure 9.
FTIR spectra of the printlet formulation powder before and after the printing process.
Figure 10.
Figure 10.
X-ray powder diffractograms of the printlet formulations after exposure to 40 °C/75% RH for a month.
Figure 11.
Figure 11.
Pharmacokinetic profiles of the printlets and compressed tablets in rabbits.
See this image and copyright information in PMC

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