TY - JOUR
T1 - Fused deposition modeling 3D printing of solid oral dosage forms containing amorphous solid dispersions
T2 - How to elucidate drug dissolution mechanisms through surface spectral analysis techniques?
AU - Parulski, Chloé
AU - Gresse, Eva
AU - Jennotte, Olivier
AU - Felten, Alexandre
AU - Ziemons, Eric
AU - Lechanteur, Anna
AU - Evrard, Brigitte
N1 - Funding Information:
This work was supported by the FEDER funds for the support in SOLPHARE project (884148- 329407). Authors want to thank Dr. Luisa Orozco from the Group of Research and Applications in Statistical Physics (Profs. Nicolas Vandewalle and Geoffroy Lumay - University of Liege, Belgium) concerning her help about texture analyzer data treatment. Authors want to tank Dr. Erwan Plougonven from the PEPs (Prof. Angélique Léonard – University of Liege, Belgium) for the computerized tomography scan analysis. Authors want to thank Dr. Alexandre Felten from the Synthesis, Irradiation & Analysis of Materials platform (University of Namur, Belgium) for TOF-SIMS experiments.
Funding Information:
This work was supported by the FEDER funds for the support in SOLPHARE project (884148- 329407). Authors want to thank Dr. Luisa Orozco from the Group of Research and Applications in Statistical Physics (Profs. Nicolas Vandewalle and Geoffroy Lumay - University of Liege, Belgium) concerning her help about texture analyzer data treatment. Authors want to tank Dr. Erwan Plougonven from the PEPs (Prof. Angélique Léonard – University of Liege, Belgium) for the computerized tomography scan analysis. Authors want to thank Dr. Alexandre Felten from the Synthesis, Irradiation & Analysis of Materials platform (University of Namur, Belgium) for TOF-SIMS experiments.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/10/15
Y1 - 2022/10/15
N2 - Many active principles belong to the second class of the Biopharmaceutics Classification System due to their low aqueous solubility. Elaboration of new solid oral forms by hot-melt extrusion and fused deposition modeling appears as a promising tool to increase the dissolution rate of these drugs. Indeed, hot-melt extrusion allows the amorphisation of drugs and forms with complex geometries are built by 3D printing. Therefore, the goal of this work is to enhance the dissolution rate of poorly soluble drugs using hot-melt extrusion coupled with fused deposition modeling. Four formulations containing Affinisol® 15LV, Kollidon® VA64 and a challenging amount of itraconazole (25 % (wt.)) were successfully printed into forms of 20, 50 and 80 % infill densities. Differential scanning calorimetry analysis has shown that itraconazole remained amorphous during 52 weeks. The drug release rate was highly improved compared to itraconazole in a crystalline form. The dissolution rate was influenced by the infill density and the polymer composition of printed forms which could modify respectively the surface to volume ratio and the distribution of the components in the printed forms. One formulation printed with 20 % infill density even had a solubility profile similar to that of Sporanox®, the commercialized drug product in Belgium.
AB - Many active principles belong to the second class of the Biopharmaceutics Classification System due to their low aqueous solubility. Elaboration of new solid oral forms by hot-melt extrusion and fused deposition modeling appears as a promising tool to increase the dissolution rate of these drugs. Indeed, hot-melt extrusion allows the amorphisation of drugs and forms with complex geometries are built by 3D printing. Therefore, the goal of this work is to enhance the dissolution rate of poorly soluble drugs using hot-melt extrusion coupled with fused deposition modeling. Four formulations containing Affinisol® 15LV, Kollidon® VA64 and a challenging amount of itraconazole (25 % (wt.)) were successfully printed into forms of 20, 50 and 80 % infill densities. Differential scanning calorimetry analysis has shown that itraconazole remained amorphous during 52 weeks. The drug release rate was highly improved compared to itraconazole in a crystalline form. The dissolution rate was influenced by the infill density and the polymer composition of printed forms which could modify respectively the surface to volume ratio and the distribution of the components in the printed forms. One formulation printed with 20 % infill density even had a solubility profile similar to that of Sporanox®, the commercialized drug product in Belgium.
KW - 3D printing
KW - Additive manufacturing
KW - Amorphous solid dispersion
KW - Fused deposition modeling
KW - Hot-melt extrusion
KW - Itraconazole
UR - http://www.scopus.com/inward/record.url?scp=85137293472&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2022.122157
DO - 10.1016/j.ijpharm.2022.122157
M3 - Article
C2 - 36055443
AN - SCOPUS:85137293472
SN - 0378-5173
VL - 626
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 122157
ER -