(M1530-01-03) In Vitro and In Vivo Characterization of Rapidly Dissolving Printlets of Isoniazid Manufactured by SLS 3D Printing

Monday, October 17, 2022

3:30 PM – 4:30 PM ET

Presenting Author(s)

Tahir Gani Khuroo, PhD (he/him/his)

Research Scientist
Texas A&M University
Stafford, Texas, United States

Main Author(s)

Tahir Gani Khuroo, PhD (he/him/his)

Research Scientist
Texas A&M University
Stafford, Texas, United States

Purpose: World-wide, Tuberculosis (TB) is the most common cause of death among the infectious diseases. In 2019, around 1.4 million deaths were reported because of TB. There is an estimation of 10 million new TB infections that were reported in 2019 and among them are 1.2 million children. Pediatric patients need dose flexible delivery systems due to variability in the physiology of children where fixed dose therapy or combinations won’t work and may lead to over or under dose in the pediatric patients. An ideal pediatric dosage form should be able to titrate doses, so that all age groups up to 17 years of children can be covered by a single product. 3D printed pediatric dosage forms offers many advantages. The dosage forms can be designed to be highly porous so that they can melt/dissolve over the tongue or it can be dispersed in a liquid just before administration to the children. The purpose of this research work is to manufacture the rapidly dissolving printlets of isoniazid (INH) by using selective laser sintering technique of 3D – printing.

Methods: A number of trials were performed on the composition of the printlets, however, the final optimized printlet composition was: INH - 50%, Candurin^® NXT Ruby Red - 3%, CCS – 0-10%, Kollicoat^® IR – 37-47%. The ingredients were passed through sieve,150 µm pore size in order to get the uniform blend. Powder ingredients were mixed in V-blender, Model VH-2 for 5 min. In each batch 63 (9×7) printlets of 4.5 mm diameter × 3 mm height were manufactured by varying the process parameters such as surface temperature (100-110 ^oC) and laser scanning speed (400-500 mm/s). Powder was sintering was done using 2.3 W blue laser (445 nm). The printlets were allowed to cool down, and then removed from the powder bed. The printlets were characterized for weight, diameter, and thickness by Vernier caliper. The disintegration time (DT) of six printlets was determined in water at 37 ◦C using a USP disintegration apparatus (Vankel Varian VK-100, NC, USA). The characterization of the printlets was done by XRDP, FTIR, DSC, weight, Micro-X-ray-CT scan, hardness, and dissolution. The pharmacokinetic evaluation of the printlets was performed on New Zealand rabbits (10 mg/Kg).

Results: Weight of the printlets from different printlet formulations varied from 10.4±0.3 to 14.4±0.4 mg. Hardness of printlets was observed to vary between 1.9±1.0 – 11.1±2.8 N. Assay of the printlets was found in the acceptable range of 98.8±2.0 to 102.0±2.0%. Disintegration time of the printlets varied from 3.0±0.0 to 63.3±5.8 seconds. The dissolution of all formulations completed in 3 minutes only. XRD and DSC showed the conversion of crystalline form of drug into amorphous. Stability studies performed showed that the printlets were stable at 40 ^oC/75% RH, since no significant changes in assay and dissolution were observed. T_max, C_max and AUC_0-_∞ of the tablets and the printlets were 0.38 and 0.63 h, 4.50±1.58 and 4.54±1.38 µg/ml, and 12.36±3.54 and 15.50±4.57 µgh/ml, respectively.

Conclusion: Rapidly dissolving printlets of INH were developed successfully using SLS – 3D printing technique. The printlets produced were highly porous that fasten disintegration and dissolution. Further, pharmacokinetic profiles of the printlets and the compressed tablets were similar (p < 0.05). In summary, the printlets were stable and the oral bioavailability was similar to that of the compressed tablets.

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