Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Sector 67 , S.A.S. Nagar 160 062 , Punjab , India.
Mol Pharm. 2018 May 7;15(5):1917-1927. doi: 10.1021/acs.molpharmaceut.8b00077. Epub 2018 Apr 20.
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 (ϕ = 41.27:58.73% w/w) and EM-2 (ϕ = 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 (σ = 138.66 MPa) of EM-1 as compared to that of EM-2 (σ = 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 (τ = 3.83 MPa) was predicted to be higher for EM-1 than EM-2 (τ = 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.
在共晶中，层状微观结构比未反应的物理混合物更有利于压片。然而，在两种二元共晶中，整体变形仍然难以实现。我们假设，具有不同成分的药物的二元共晶，具有不同的氢键维度和晶体结构，将有助于理解整体变形行为中的结构完整性。剪切分子固体 (FXT Q) 与粘弹性晶体 (ASP I) 和脆性晶体 (PCM I) 具有相同的组成，分别形成 EM-1 (ϕ = 41.27:58.73% w/w) 和 EM-2 (ϕ = 41.10:58.90% w/w)。过剩热力学函数是由高能微观结构（非键相互作用）和非晶相界（在 CLSM 下可见）贡献的。能量色散分析能够识别出更高原子在异质表面上的相对分布。在一定的压实压力范围内，与 EM-2（FXT Q-PCM I）相比，EM-1（FXT Q-ASP I）表现出更高的压缩性、拉伸强度和可压缩性（CTC 曲线）。EM-1 的真实屈服强度（σ = 138.66 MPa）低于 EM-2（σ = 166.66 MPa），表明其具有更好的变形性能和初始塑性，这可以从“出模” Heckel 分析中量化。根据 Ryshkewitch 分析，在零孔隙率下的拉伸强度（τ = 3.83 MPa）预计将高于 EM-2（τ = 2.54 MPa）。EM-1 的较高结合强度归因于 ASP I（0D）的真实密度和各向同性范德华相互作用的额外影响。相比之下，EM-2 表现出较低的压缩性和可压缩性，具有 PCM I（1D）的人字形分子堆积和共同的剪切成分（FXT Q（1D））。这项研究证实，第二成分的内在变形和化学性质在晶体固溶体聚集体的压片性能中更大程度上决定了压缩性和可压缩性的趋势。
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