Górniak Agata, Złocińska Adrianna, Trojan Mateusz, Pęcak Adrianna, Karolewicz Bożena
Laboratory of Elemental Analysis and Structural Research, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Department of Drug Form Technology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Pharmaceutics. 2022 Apr 22;14(5):912. doi: 10.3390/pharmaceutics14050912.
Two active pharmaceutical ingredients (APIs) with limited solubility, simvastatin and ezetimibe, prepared as a drug-drug solid dispersion (SD) was evaluated for physicochemical, microstructural, and aqueous dissolution properties. The simvastatin-ezetimibe SD was prepared using the co-grinding method in a wide range of weight fractions and differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to perform the phase composition analysis. DSC studies confirmed that simvastatin and ezetimibe form a simple eutectic phase equilibrium diagram. Analysis of Fourier transform infrared spectroscopy (FTIR) studies excluded strong interactions between the APIs. Our investigations have revealed that all studied dispersions are characterized by substantially improved ezetimibe dissolution regardless of simvastatin content, and are best when the composition oscillates near the eutectic point. Data obtained in our studies provide an opportunity for the development of well-formulated, ezetimibe-simvastatin fixed-dose combinations (for hypercholesterolemia treatment) with reduced ezetimibe dosages based on its dissolution improvement.
对采用共研磨法制备的、含有两种低溶解度活性药物成分（API）——辛伐他汀和依折麦布的药物-药物固体分散体（SD）进行了物理化学、微观结构和水溶解性质评估。在较宽的重量分数范围内制备了辛伐他汀-依折麦布固体分散体，并采用差示扫描量热法（DSC）和X射线粉末衍射（XRPD）进行相组成分析。DSC研究证实，辛伐他汀和依折麦布形成了简单的低共熔相平衡图。傅里叶变换红外光谱（FTIR）研究分析排除了活性药物成分之间的强相互作用。我们的研究表明，所有研究的分散体均具有显著改善的依折麦布溶出度，与辛伐他汀含量无关，且当组成在低共熔点附近波动时效果最佳。我们研究中获得的数据为开发配方良好的、基于依折麦布溶出度改善而降低其剂量的依折麦布-辛伐他汀固定剂量组合（用于治疗高胆固醇血症）提供了机会。
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