Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients

The focus of current studies was to fabricate dose flexible printlets of dapsone (DDS) for pediatric patients by selective laser sintering (SLS) 3D printing method, and evaluate its physicochemical, patient in-use stability, and pharmacokinetic attributes. Eight formulations were fabricated using Kollicoat^® IR, Eudragit^® L-100-55 and StarCap^®as excipients and evaluated for hardness, disintegration, dissolution, amorphous phase by differential scanning calorimetry and X-ray powder diffraction, in-use stability at 30 ^oC/75% RH for a month, and pharmacokinetic study in Sprague Dawley rats.

The hardness, and disintegration of the printlets varied from 2.6±1.0 (F4) to 7.7±0.9 (F3) N and 2.0±0.4 (F2) to 7.6±0.6 (F3) sec, respectively. The drug was partially present as an amorphous form in the printlets. The drug was completely (>85%) dissolved in 20 min. No change in drug form or dissolution extent was observed after storage at in use condition. Pharmacokinetic profiles of both formulations (tablets and printlets) were almost superimposable with no statistical difference in pharmacokinetic parameters (T_max, C_max, and AUC_0-¥)between formulations (p>0.05).

Values of EC₅₀ (half maximal effective concentration) and EC₉₀ (maximal concentration inducing 90% maximal response) were 0.50±0.15 and 1.32±0.26 mM, 0.41±0.06 and 1.11±0.21, and 0.42±0.13 and 1.36±0.19 mM for DDS, printlet and tablet formulations, respectively, and differences were statistically insignificant (p>0.05). In conclusion, tablet and printlet formulations are expected to be clinical similar, thus clinically interchangeable.

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Materials

DDS (Alfa Aesar, Haverhill, MA), Eudragit® L-100-55 (Evonik Rohm GmbH, Germany), StarCap® 1500 (Color-con, Harleysville, PA),  Candurin® NXT Ruby Red (Merck, Darmstadt, Germany), and  Kollicoat® IR (BASF, Ludwigshafen, Germany) were used as received. Methanol (MeOH), N-methyl pyrrolidone (NMP), dimethylsulfoxide (DMSO), glacial acetic acid, acetonitrile (ACN), and formic acid were purchased from Fisher Scientific, Asheville, NC. Deuter-ated DDS (DDS-d4) and N-acetyl DDS was obtained from Toronto Research Chemicals, Ontario, Canada. Heparinized rat plasma was purchased from BioChemed Services, Win-chester, VA. All reagents were of analytical grade or better.

Khan, A.A., Khuroo, T., Mohamed, E.M. et al. Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients. AAPS PharmSciTech 25, 217 (2024). https://doi.org/10.1208/s12249-024-02935-2

Read also our introduction article:

CPHI Milan 2024 – with a focus on excipients