(T1030-01-04) Formulation Development and Characterization of Isoniazid-Pyridoxine Combination Gummies Using an Extrusion-Based 3D Printer

Purpose: This study aimed to formulate and evaluate Isoniazid-Pyridoxine-loaded (INH-PDX) gummies for use in pediatric and geriatric populations and to study the applicability of semisolid-extrusion-based BIO X 3D printer in preparation of immediate-release gummy formulations. This contemporary approach aims to provide a new strategy for preparing dual-drug-loaded formulations used to treat tuberculosis and effectively meets the need for on-demand and personalized medicine, which can ultimately be commercialized.

Methods: Gelatin was hydrated and heated. The drugs were added to the hydrated gelatin mixture along with the antioxidants followed by the addition of a separately hydrated carrageenan component. The premix was introduced in a printing cartridge. The 3D-printed gummies were formulated using a BIO X 3D printer. Initially, various excipients and printing parameters were screened to determine the best formulation for loading the drugs and printing an intact gummy. These gummies were evaluated for appearance, weight, drug content, drug-drug and drug-excipient compatibility, texture, and in vitro drug release. Additionally, the gummy matrix was evaluated for rheological characteristics. Moreover, the gummy and gummy matrix stability was checked over 30 days (25 ± 2°C and 5 ± 3°C) to evaluate the applicability of the technology for on-demand printing.

Results: Gummies with dimensions 14x14x7 mm were formulated using BIO X 3D Printer. The lead formulation showed more than 85% drug release of both drugs in 30 minutes. All fabricated gummies and the printing premixes were stable over 30-day storage at room temperature (25 ± 2°C) and refrigerated conditions (5 ± 3°C) for drug content and in vitro drug release. The developed INH-PDX gummies exhibited optimum mechanical properties including hardness, adhesiveness, springiness, cohesiveness, gumminess, chewiness, and resilience favorable for forming a strong gummy. Rheological evaluations of the printing premix revealed that the premix showed thixotropic, viscoelastic, and shear-thinning behavior ideal for semi-solid extrusion-based 3D printing.

Conclusion: Immediate-release 3D printed gummy formulations were successfully prepared using semisolid extrusion via Bio X 3D Printer. In vitro characterization of the lead formulation indicates an immediate drug release performance. Ideal rheological characteristics of the premix indicate the suitability of the premix for successful printing and maintaining the structure of the gummy. In addition, the stability studies indicated that the lead formulation was stable at 25°C ± 2°C and 5°C ± 3°C conditions for 30 days showing no change in the drug content and the in vitro release. The printing material can be stored in the cartridge for 30 days and printed whenever required. The fabricated gummies could improve patient compliance and could be printed in personalized doses for on-demand drug product printing.

References: 1. Han X, Kang D, Liu B, Zhang H, Wang Z, Gao X, et al. Feasibility of developing hospital preparation by semisolid extrusion 3D printing: personalized amlodipine besylate chewable tablets. Pharm Dev Technol. 2022 Feb;27(2):164–74.
2. Seoane-Viaño I, Januskaite P, Alvarez-Lorenzo C, Basit AW, Goyanes A. Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges. J Control Release Off J Control Release Soc. 2021 Apr 10;332:367–89.


Shear Recovery test for thixotropy evaluation of the gummy matrix


Dissolution Profiles of INH-PDX 3D-Printed Gummy Formulations (Day 0)

Dissolution Profiles of INH-PDX 3D-Printed Gummy Formulations (Day 30 at 25°C ± 2°C)