The aim of this study was to characterize a 1:1 molar ratio of a pharmacologically relevant co-amorphous atorvastatin-irbesartan (ATR-IRB) system obtained by quench cooling of the crystalline ATR/IRB physical mixture for potential use in the fixed-dose combination therapy. The system was characterized by employing standard differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and intrinsic dissolution rate studies. Quantum mechanical calculations were performed to obtain information regarding intermolecular interactions in the studied co-amorphous ATR-IRB system. The co-amorphous formulation showed a significant improvement in the intrinsic dissolution rate (IDR) of IRB over pure crystalline as well as its amorphous counterpart. An unusual behavior was observed for ATR, as the IDR of ATR in the co-amorphous formulation was slightly lower than that of amorphous ATR alone. Short-term physical aging studies of up to 8 h proved that the ATR-IRB co-amorphous system remained in the amorphous form. Furthermore, no physical aging occurred in the co-amorphous system. FT-IR, density functional theory calculations, and analysis of T_g value of co-amorphous system using the Couchman–Karasz equation revealed the presence of molecular interactions between APIs, which may contribute to the increased physical stability.

中文翻译：

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共非晶阿托伐他汀-厄贝沙坦系统的理化特性及其在固定剂量联合治疗中的潜在应用

这项研究的目的是表征药理学上相关的无定形阿托伐他汀-厄贝沙坦（ATR-IRB）系统的1：1摩尔比，该系统可通过对结晶ATR / IRB物理混合物进行骤冷冷却而获得，可用于固定剂量联合疗法。该系统的特点是采用标准差示扫描量热法（DSC），傅立叶变换红外光谱（FT-IR）和固有溶解速率研究。进行了量子力学计算，以获取有关研究的非晶ATR-IRB系统中分子间相互作用的信息。与纯晶体及其无定形对应物相比，该无定形制剂显示出IRB的固有溶解速率（IDR）显着提高。观察到ATR的异常行为，因为无定形配方中ATR的IDR略低于单独的无定形ATR。长达8小时的短期物理老化研究证明，ATR-IRB共非晶体系仍以非晶形式存在。此外，在共非晶体系中没有发生物理老化。FT-IR，密度泛函理论计算和分析使用Couchman-Karasz方程的共非晶系统的T _g值表明，API之间存在分子相互作用，这可能有助于提高物理稳定性。