Physico-chemical characterisation of three-component co-amorphous systems generated by a melt-quench method

Abstract

The purpose of this work was to evaluate the possibility of creating a ternary co-amorphous system and to determine how the properties of a co-amorphous material are altered by the addition of a selected third component. Piroxicam and indomethacin form a stable co-amorphous with the T g above room temperature. The third component added was selected based on tendency to crystallise (benzamide, caffeine) or form amorphous (acetaminophen, clotrimazole) on cooling. Generated co-amorphous systems were characterised with TGA, HSM, DSC, FTIR and XRD. Stable ternary co-amorphous systems were successfully generated, which were confirmed using XRD, DSC and FTIR analysis. In all cases, T g of the ternary system was lower than the T g of the binary system, although higher than that of the individual third component. Upon storage for 4 weeks, all created ternary systems showed significantly smaller variation in T g compared to the binary system. Stable three-component co-amorphous systems can be generated via melt-quench method using either a crystalline or an amorphous third component. Addition of third component can alter the T g of co-amorphous system and in all cases created more stable co-amorphous system upon storage. Physical parameters may not be sufficient in predicting the resulting T g ; therefore, knowledge of chemical interaction must be brought into equation as well.

Preparation of Spray Dried Coamorphous Solids to Improve the Solubility and Dissolution Rate of Atorvastatin Calcium

“…All these shifts particularly in AC indicate the formation of intermolecular interactions between the functional group components [37]. The functional groups of AC which form intermolecular interactions with coamorphous AC-INA and AC-MA are strong proton acceptors and donors of hydrogen bond, therefore hydrogen bonding is present [22,38].…”

“…The FTIR spectra of coamorphous AC-INA and AC-MA ( Figure 3) showed broad peaks and reduced intensity when compared to that of crystalline AC (Figure 3). This broadening and reduction were attributed to amorphization caused by the disruption of the crystal lattice and the lack of long-range orders for a specific bond [17,19,37]. Furthermore, the absorption peaks of coamorphous AC-INA exhibited shifts from lower to higher wave numbers (3364 to 3415 cm-1, 3056 to 3069 cm-1, 1650 to 1664 cm-1, and 1216 to 1223 cm-1).…”

Amorphous and Co-Amorphous Olanzapine Stability in Formulations Intended for Wet Granulation and Pelletization

“…Co-amorphous systems (CAMs), i.e., dispersions at the molecular level of drugs in low molecular weight compounds, have gained special interest [ 17 , 18 , 19 , 20 , 21 ] by enhancing the stability of the amorphous systems produced while increasing the solubility of the drugs [ 20 , 22 ]. The combination of drugs with a second substance (either a pharmaceutically accepted excipient or a second drug providing a sensible therapeutic combination [ 17 , 23 , 24 , 25 ]) enables the stabilization of the amorphous system, due to the establishment of intermolecular bonds between the two entities, often with a higher glass transition temperature (T g ) than the pure amorphous drug(s) or the physical mixture of the individual components [ 23 , 26 ].…”

Amorphous solid dispersions of ritonavir by melt-quenching

“…Time required for complete solidification will depends on temperature conditions and formulation composition, once complete solidification occurred, RASDs were milled, passed through sieve for uniform size distribution and stored in air sealed containers. (Mistry, P et al, 2017, D'Angelo, A et al, 2018…”