Cell culture and pharmacokinetic evaluation of a solid dosage formulation containing a water-insoluble orphan drug manufactured by FDM-3DP technology

Saydam M., TİMUR S. S., Vural M., TAKKA S.

INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol.628, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 628
  • Publication Date: 2022
  • Doi Number: 10.1016/j.ijpharm.2022.122307
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Additive manufacturing, 3DP, Orphan drug, Solid dosage formulation, Dissolution, Intrinsic dissolution, Solid dispersion, Cell culture, MTT, Pharmacokinetic, RUFINAMIDE, CYTOTOXICITY
  • Hacettepe University Affiliated: Yes


The in-vitro cytotoxicity, in-vitro permeability and in-vivo pharmacokinetics of a BCS Class-II drug - rufinamide - in a 3DP tablet formulation were evaluated. The cytotoxicity of the 3DP tablet formulation was evaluated with an MTT test; in-vitro permeability was evaluated with a Caco-2 cell culture study; and in-vivo pharmacokinetics were evaluated in Wistar albino male rats. The pharmacokinetic studies were performed following a two -sequence and single-period design approach. The highest Caco-2 permeability was obtained with the 3DP tablet formulation; and the highest cell viability was achieved with the 3DP tablet in both the Hep G2 and Caco-2 cell lines. In the in-vivo pharmacokinetic study, AUC and Cmax values were higher in the 3DP tablet formulation than in the Inovelon (R) film tablet at a 40 mg/kg dose. Thanks to the increased solubility of the active substance, higher in-vitro permeability and in-vivo absorption were achieved with the 3DP tablet formulation, and with lower cytotoxicity. Based on these promising findings, the 3DP tablet formulation can be considered an effective lower-dose treatment than commercial preparations.