Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations
Drop-on-powder 3D printing is able to produce highly drug loaded solid oral dosage forms. However, this technique is mainly limited to well soluble drugs. The majority of pipeline compounds is poorly soluble, though, and requires solubility enhancement, e.g., via formation of amorphous solid dispers...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | International Journal of Pharmaceutics: X |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156722000421 |
| _version_ | 1797798663510032384 |
|---|---|
| author | Nadine Gottschalk Alicia Burkard Julian Quodbach Malte Bogdahn |
| author_facet | Nadine Gottschalk Alicia Burkard Julian Quodbach Malte Bogdahn |
| author_sort | Nadine Gottschalk |
| collection | DOAJ |
| description | Drop-on-powder 3D printing is able to produce highly drug loaded solid oral dosage forms. However, this technique is mainly limited to well soluble drugs. The majority of pipeline compounds is poorly soluble, though, and requires solubility enhancement, e.g., via formation of amorphous solid dispersions. This study presents a detailed and systematic development approach for the production of tablets containing high amounts of a poorly soluble, amorphized drug via drop-on-powder 3D printing (also known as binder jetting). Amorphization of the compound was achieved via hot-melt extrusion using the exemplary system of the model compound ketoconazole and copovidone as matrix polymer at drug loadings of 20% and 40%. The milled extrudate was used as powder for printing and the influence of inks and different ink-to-powder ratios on recrystallization of ketoconazole was investigated in a material-saving small-scale screening. Crystallinity assessment was performed using differential scanning calorimetry and polarized light microscopy to identify even small traces of crystallinity. Printing of tablets showed that the performed small-scale screening was capable to identify printing parameters for the development of amorphous and mechanically stable tablets via drop-on-powder printing. A stability study demonstrated physically stable tablets over twelve weeks at accelerated storage conditions. |
| first_indexed | 2024-03-13T04:07:14Z |
| format | Article |
| id | doaj.art-53c740fbdfca43c39ad4d680248942c5 |
| institution | Directory Open Access Journal |
| issn | 2590-1567 |
| language | English |
| last_indexed | 2024-03-13T04:07:14Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj.art-53c740fbdfca43c39ad4d680248942c52023-06-21T06:59:09ZengElsevierInternational Journal of Pharmaceutics: X2590-15672023-12-015100151Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitationsNadine Gottschalk0Alicia Burkard1Julian Quodbach2Malte Bogdahn3Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany; Merck KGaA, Darmstadt, GermanyMerck KGaA, Darmstadt, GermanyInstitute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, NetherlandsMerck KGaA, Darmstadt, Germany; Corresponding author.Drop-on-powder 3D printing is able to produce highly drug loaded solid oral dosage forms. However, this technique is mainly limited to well soluble drugs. The majority of pipeline compounds is poorly soluble, though, and requires solubility enhancement, e.g., via formation of amorphous solid dispersions. This study presents a detailed and systematic development approach for the production of tablets containing high amounts of a poorly soluble, amorphized drug via drop-on-powder 3D printing (also known as binder jetting). Amorphization of the compound was achieved via hot-melt extrusion using the exemplary system of the model compound ketoconazole and copovidone as matrix polymer at drug loadings of 20% and 40%. The milled extrudate was used as powder for printing and the influence of inks and different ink-to-powder ratios on recrystallization of ketoconazole was investigated in a material-saving small-scale screening. Crystallinity assessment was performed using differential scanning calorimetry and polarized light microscopy to identify even small traces of crystallinity. Printing of tablets showed that the performed small-scale screening was capable to identify printing parameters for the development of amorphous and mechanically stable tablets via drop-on-powder printing. A stability study demonstrated physically stable tablets over twelve weeks at accelerated storage conditions.http://www.sciencedirect.com/science/article/pii/S2590156722000421Drop-on-powder printingBinder jettingAmorphous solid dispersionSolubility enhancement3D PrintingProcess development |
| spellingShingle | Nadine Gottschalk Alicia Burkard Julian Quodbach Malte Bogdahn Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations International Journal of Pharmaceutics: X Drop-on-powder printing Binder jetting Amorphous solid dispersion Solubility enhancement 3D Printing Process development |
| title | Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations |
| title_full | Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations |
| title_fullStr | Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations |
| title_full_unstemmed | Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations |
| title_short | Drop-on-powder 3D printing of amorphous high dose oral dosage forms: Process development, opportunities and printing limitations |
| title_sort | drop on powder 3d printing of amorphous high dose oral dosage forms process development opportunities and printing limitations |
| topic | Drop-on-powder printing Binder jetting Amorphous solid dispersion Solubility enhancement 3D Printing Process development |
| url | http://www.sciencedirect.com/science/article/pii/S2590156722000421 |
| work_keys_str_mv | AT nadinegottschalk droponpowder3dprintingofamorphoushighdoseoraldosageformsprocessdevelopmentopportunitiesandprintinglimitations AT aliciaburkard droponpowder3dprintingofamorphoushighdoseoraldosageformsprocessdevelopmentopportunitiesandprintinglimitations AT julianquodbach droponpowder3dprintingofamorphoushighdoseoraldosageformsprocessdevelopmentopportunitiesandprintinglimitations AT maltebogdahn droponpowder3dprintingofamorphoushighdoseoraldosageformsprocessdevelopmentopportunitiesandprintinglimitations |