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. 2022 Jun;12(3):424-435.
doi: 10.1016/j.jpha.2021.09.010. Epub 2021 Sep 20.

Compatibility and stability studies involving polymers used in fused deposition modeling 3D printing of medicines

Ihatanderson A Silva  1 , Ana Luiza Lima  1 , Tais Gratieri  1 , Guilherme M Gelfuso  1 , Livia L Sa-Barreto  2 , Marcilio Cunha-Filho  1
Affiliations

Compatibility and stability studies involving polymers used in fused deposition modeling 3D printing of medicines

Ihatanderson A Silva et al. J Pharm Anal. 2022 Jun.

Abstract

One of the challenges in developing three-dimensional printed medicines is related to their stability due to the manufacturing conditions involving high temperatures. This work proposed a new protocol for preformulation studies simulating thermal processing and aging of the printed medicines, tested regarding their morphology and thermal, crystallographic, and spectroscopic profiles. Generally, despite the strong drug-polymer interactions observed, the chemical stability of the model drugs was preserved under such conditions. In fact, in the metoprolol and Soluplus® composition, the drug's solubilization in the polymer produced a delay in the drug decomposition, suggesting a protective effect of the matrix. Paracetamol and polyvinyl alcohol mixture, in turn, showed unmistakable signs of thermal instability and chemical decomposition, in addition to physical changes. In the presented context, establishing protocols that simulate processing and storage conditions may be decisive for obtaining stable pharmaceutical dosage forms using three-dimensional printing technology.

Keywords: Drug-polymer compatibility; Hot-melt extrusion; Preformulation; Thermal analysis; Three-dimensional printing.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Differential exploratory calorimetry (DSC) curves of paracetamol (PCM) as supplied and binary mixtures PCM-Eudragit® L100 (EUL), PCM-Parteck® MXP (PVA), PCM-Plasdone® (PVPVA), and PCM-Soluplus® (SOL) untreated and subjected to double heating (heated) and different aging time (30, 60, and 90 days). The PCM melting peak is shaded.
Fig. 2
Fig. 2
Derivative thermogravimetric analysis (DTG) curves of PCM as supplied and binary mixtures PCM-EUL, PCM-PVA, PCM-PVPVA, and PCM-SOL untreated and subjected to double heating (heated) and different aging time (30, 60, and 90 days). The onset decomposition temperature and the temperature peaks of the decomposition phases are indicated.
Fig. 3
Fig. 3
Fourier transform infrared spectroscopy (FTIR) spectra of PCM as supplied and binary mixtures PCM-EUL, PCM-PVA, PCM-PVPVA, and PCM-SOL untreated and subjected to double heating (heated) and different aging time (30, 60, and 90 days). The bands related to the PCM functional groups are highlighted in the spectra and correlated with its chemical structure. The correlation coefficient (r) among the untreated and treated samples is also displayed.
Fig. 4
Fig. 4
X-ray powder diffraction (XRPD) diffractograms and optical micrographs of PCM as supplied and binary mixtures PCM-EUL, PCM-PVA, PCM-PVPVA, and PCM-SOL untreated and aged. The characteristic peaks of crystal PCM are shaded in diffractograms (15.45°, 18.15°, 23.45°, 24.35°, and 26.50°). The photomicrography magnification was ×4.5.
Fig. 5
Fig. 5
DSC curves of metoprolol tartrate (MTL) as supplied and binary mixtures MTL-EUL, MTL-PVA, MTL-PVPVA, and MTL-SOL untreated and subjected to double heating (heated) and different aging time (30, 60, and 90 days). The MTL melting peak is shaded.
Fig. 6
Fig. 6
DTG curves of metoprolol tartrate (MTL) as supplied and binary mixtures MTL-EUL, MTL-PVA, MTL-PVPVA, and MTL-SOL untreated and subjected to double heating (heated) and different aging time (30, 60, and 90 days). The onset decomposition temperature and the temperature peaks of the decomposition phases are indicated.
Fig. 7
Fig. 7
XRPD diffractograms and optical micrographs of MTL as supplied and binary mixtures MTL-EUL, MTL-PVA, MTL-PVPVA, and MTL-SOL untreated and aged. The characteristic peaks of crystal MTL are shaded in diffractograms (10.55°, 11.85°, 19.35°, 20.30°, 23.10°, and 23.95°). The photomicrography magnification was ×4.5.
Fig. 8
Fig. 8
FTIR spectra of MTL as supplied and binary mixtures MTL-EUL, MTL-PVA, MTL-PVPVA, and MTL-SOL untreated and subjected to double heating (heated) and different aging time (30, 60, and 90 days). The bands related to the PCM functional groups are highlighted in the spectra and correlated with its chemical structure. The correlation coefficient (r) among the untreated and treated samples is also displayed.
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