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. 2021 Sep 26;13(19):3282.
doi: 10.3390/polym13193282.

Investigating the Potential Plasticizing Effect of Di-Carboxylic Acids for the Manufacturing of Solid Oral Forms with Copovidone and Ibuprofen by Selective Laser Sintering

Yanis Abdelhamid Gueche  1 , Noelia M Sanchez-Ballester  1   2 , Bernard Bataille  1 , Adrien Aubert  1 , Jean-Christophe Rossi  3 , Ian Soulairol  1   2
Affiliations

Investigating the Potential Plasticizing Effect of Di-Carboxylic Acids for the Manufacturing of Solid Oral Forms with Copovidone and Ibuprofen by Selective Laser Sintering

Yanis Abdelhamid Gueche et al. Polymers (Basel). .

Abstract

In selective laser sintering (SLS), the heating temperature is a critical parameter for printability but can also be deleterious for the stability of active ingredients. This work aims to explore the plasticizing effect of di-carboxylic acids on reducing the optimal heating temperature (OHT) of polymer powder during SLS. First, mixtures of copovidone and di-carboxylic acids (succinic, fumaric, maleic, malic and tartaric acids) as well as formulations with two forms of ibuprofen (acid and sodium salt) were prepared to sinter solid oral forms (SOFs), and their respective OHT was determined. Plasticization was further studied by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Following this, the printed SOFs were characterized (solid state, weight, hardness, disintegration time, drug content and release). It was found that all acids (except tartaric acid) reduced the OHT, with succinic acid being the most efficient. In the case of ibuprofen, only the acid form demonstrated a plasticizing effect. DSC and FTIR corroborated these observations showing a decrease in the glass transition temperature and the presence of interactions, respectively. Furthermore, the properties of the sintered SOFs were not affected by plasticization and the API was not degraded in all formulations. In conclusion, this study is a proof-of-concept that processability in SLS can improve with the use of di-carboxylic acids.

Keywords: di-carboxylic acids; heating temperature; plasticizers; printability; selective laser sintering; solid oral forms.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of (a) copovidone KVA64, (b) ibuprofen acid, (c) ibuprofen sodium salt, (d) succinic acid, (e) fumaric acid, (f) maleic acid, (g) L-malic acid, (h) L-tartaric acid.
Figure 2
Figure 2
Relationship between glass transition temperatures and optimal heating temperatures at different ratios of succinic acid for mixtures of KVA64/SA and mixtures of KVA64/IbuNa/SA.
Figure 3
Figure 3
FTIR spectrums of KVA64, IbuNa, IbuAc and printed SOFs: (a) from 400 to 4000 cm−1, (b) from 1500 to 1900 cm−1.
Figure 4
Figure 4
FTIR spectrums of KVA64, FA, MA, MLA, TA and printed SOFs: (a) from 400 to 4000 cm−1, (b) from 1500 to 1900 cm−1.
Figure 5
Figure 5
FTIR spectrums of KVA64, SA and printed SOFs: (a) from 400 to 4000 cm−1, (b) from 1500 to 1900 cm−1.
Figure 6
Figure 6
FTIR spectrums of KVA64, SA, IbuNa and printed SOFs: (a) from 400 to 4000 cm−1, (b) from 1500 to 1900 cm−1.
Figure 7
Figure 7
XRPD patterns: (a) KVA64, IbuNa, IbuAc and their sintered SOFs, (b) FA, MA, MLA, TA and their sintered SOFs, (c) SA and its sintered SOFs, (d) IbuNa, SA and their sintered SOFs.
Figure 7
Figure 7
XRPD patterns: (a) KVA64, IbuNa, IbuAc and their sintered SOFs, (b) FA, MA, MLA, TA and their sintered SOFs, (c) SA and its sintered SOFs, (d) IbuNa, SA and their sintered SOFs.
Figure 8
Figure 8
Dissolutions profiles of the different SOFs prepared with drugs and the physical mixtures of KVA64 95%/IbuNa 5% and KVA64 95%/IbuAc 5%.
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