*4.1. Solid-State Characterization*

The overlay of DSC heating scans and XRPD patterns for RIV, MAL and RIV-MAL Co are presented in Figures 2 and 3, respectively. The DSC heating curve of the RIV crystals displayed a melting endotherm at 230.5 ◦C (Tm, onset) with a heat of fusion (ΔHf) of 118.6 J/g, which matches to the melting temperature of rivaroxaban form I (Figure 2). The XRPD pattern of the generated RIV sample exhibited sharp diffraction peaks at 2θ values of 9.1◦, 12.2◦, 14.4◦, 16.6◦, 17.6◦, 18.2◦, 19.6◦, 20.0◦, 21.8◦, 22.6◦, 23.5◦, 24.1◦, 24.8◦, 25.8◦, 26.8◦, 29.6◦, 30.3◦, 31.9◦ ± 0.2◦ (Figure 3). The obtained diffraction pattern matches to the calculated powder pattern (CCDC identification code—LEMSOO01, deposition no. 1854617) [10] and the peak positions correspond to the values reported for RIV form I. The DSC and XRPD data together confirmed the identity and solid form purity of RIV sample generated for the compaction study.

**Figure 2.** DSC heating curves overlay for RIV, MAL, and RIV-MAL Co Samples.

**Figure 3.** Overlay of XRPD diffractograms for RIV, MAL, and RIV-MAL Co Samples.

The DSC heating curve of MAL sample showed a broad endothermic event between 85.0◦ to 109.0 ◦C (related to solid-solid phase transition) followed by a sharp melting endotherm at 135.0 ◦C (Tm, onset), (ΔHf ≈ 235.9 J/g) [38]. The XRPD pattern of the sample showed sharp diffraction peaks, which correspond to the β form of MAL.

As shown in the DSC analysis of the RIV-MAL Co, the sample showed a transition point between 110 to 122 ◦C (related to solid to solid phase transition), followed by the endothermic peak corresponding to cocrystal melting at 167.9 ◦C (ΔHf is ~36 J/g)[10]. Following the cocrystal melting, the exothermic event (recrystallization of RIV) and the endothermic at ~230 ◦C (melting of the recrystallized RIV) were observed. The above-thermal events were consistent with the previously reported behaviour of RIV-MAL Co [10]. The experimental diffraction pattern of RIV-MAL Co sample (Figure 3) matched the calculated powder pattern obtained from single-crystal data reported by our laboratory (CCDC identification code- YORVEJ, deposition No. 1854618) [10]. Thus, DSC and XRPD together confirmed a solid form purity of the scale-up batches.

### *4.2. Particle Level and Bulk Level Attributes*

Particle size analysis revealed that all three solids had similar *D50* and *D90* values (Table 1). Similar particle size distribution allows better comparison of compaction behavior of these solids at the molecular and supramolecular level. MAL, RIV, and the cocrystal had a moisture content of less than 0.3% *w*/*w* (Table 1). MAL had a significantly higher true density value (1.628 ± 0.001 g/cm3) as compared to RIV and MAL (1.536 ± 0.005 g/cm<sup>3</sup> for RIV and 1.534 ± 0.007 g/cm3).


**Table 1.** Physical Characterization of MAL, RIV, and RIV-MAL Co.

Values in parentheses indicate standard deviation (SD), n = 3. PSD—Particle size distribution, SSA—Specific surface area, MC—Moisture content.
