Molecular Understanding and Implication of Structural Integrity in the Deformation Behavior of Binary Drug-Drug Eutectic Systems.

In eutectic, a lamellar microstructure offers better tableting than that of the nonreacted physical mixture. However, bulk deformation remains elusive in two binary eutectics. We hypothesized that the binary eutectic of a drug with different components, having different H-bonding dimensionalities and crystal structure, shall allow the understanding of the structural integrity in the bulk deformation behavior. The shearing molecular solid (FXT Q) shared a common composition with the viscoelastic crystal (ASP I) and brittle (PCM I), forming EM-1 (ϕ1 = 41.27:58.73% w/w) and EM-2 (ϕ2 = 41.10:58.90% w/w), respectively. The excess thermodynamic functions were contributed by high energy microstructures (nonbonding interactions) along incoherent phase boundaries (visualized under CLSM). The energy dispersive analysis enabled the recognition of the relative distribution of higher atoms over the heterogeneous surface. EM-1 (FXT Q-ASP I) demonstrated higher compressibility, tensile strength, and compactibility (CTC profile) compared to those of EM-2 (FXT Q-PCM I) over a range of applied compaction pressures. The lower true yield strength (σ0(EM-1) = 138.66 MPa) of EM-1 as compared to that of EM-2 (σ0(EM-2) = 166.66 MPa) suggested a better deformation performance and incipient plasticity quantified from the "out-of-die" Heckel analysis. From Ryshkewitch analysis, the tensile strength at zero porosity (τ01 = 3.83 MPa) was predicted to be higher for EM-1 than EM-2 (τ02 = 2.54 MPa). The higher bonding strength of EM-1 was contributed to the additional influence of true density and isotropic van der Waals interactions of ASP I (0D). In contrast, EM-2 demonstrated lower compressibility and compactibility, having herringbone molecular packing of PCM I (1D) with a common shearing component (FXT Q (1D)). This study confirmed that the intrinsic deformational and chemical nature of the second component defined the compressibility and compactibility tendency to a greater extent in the tableting performance of conglomerates of crystalline solid solution.