4.7 Article

Nanocrystal-based 3D-printed tablets: Semi-solid extrusion using melting solidification printing process (MESO-PP) for oral administration of poorly soluble drugs

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 611, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2021.121311

Keywords

MESO-PP 3D printing; Nanocrystals; Printlets; Albendazole

Funding

  1. Universidad Nacional de Cordoba (Argentina)
  2. CONICET (Argentina)
  3. Agencia Nacional de Investigacion y Desarrollo (ANID), Chile [3200384]
  4. Fondap [15130011]

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This study is the first to report the inclusion of nanocrystals in 3D-printed tablets using the MESO-PP printing technique, which successfully incorporated ABZ nanocrystals in high concentrations. Physicochemical analyses showed no impact of the NCs on the ink's crystallinity and chemical properties, while also demonstrating improved drug dissolution rates in the printlets.
This is the first report on the inclusion of nanocrystals (NCs) within 3D-printed oral solid dosage forms -3Dprinted tablets or printlets- produced by the Melting Solidification Printing Process (MESO-PP) 3D printing technique. This method allowed the incorporation of albendazole (ABZ) nanocrystals in a concentration of up to 50% w/w, something not achieved in conventional tablets. An ink of PEG 1500/propylenegycol was used as a carrier and no physicochemical interactions or crystallinity modifications were observed due to the inclusion of ABZ-NCs into the ink, as demonstrated by TGA, DSC, XRD and FT-IR. In particular, the relative crystallinity of the ink loaded with NCs was 97.8% similar to the physical mixture of the components. Moreover, the presence of NCs was observed in the surface and matrix of the printlets by SEM. In addition, the printlet NCs demonstrated to be more effective than NCs included in hard gelatin capsules in improving drug dissolution in HCl 0.1 N. The particle size, crystallinity and chemical stability of the nanocrystals was maintained before and after 180 days of storage. Thus, these findings exhibit relevant pharmaceutical potential for developing stable, fast-release, oral, solid dosage forms of poorly soluble drugs combining 3D printing and nanocrystals. Additionally, this technique could be applied for printing objects using different types of nanocrystals embedded in low melting temperature polymers.

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