*Article* **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 <sup>1</sup> , Noelia M. Sanchez-Ballester 1,2, Bernard Bataille <sup>1</sup> , Adrien Aubert <sup>1</sup> , Jean-Christophe Rossi <sup>3</sup> and Ian Soulairol 1,2,\***


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