Albadarin Ahmad B, Potter Catherine B, Davis Mark T, Iqbal Javed, Korde Sachin, Pagire Sudhir, Paradkar Anant, Walker Gavin
Synthesis and Solid State Pharmaceutical Cluster (SSPC), Bernal Institute, University of Limerick, Limerick, Ireland.
Synthesis and Solid State Pharmaceutical Cluster (SSPC), Bernal Institute, University of Limerick, Limerick, Ireland.
Int J Pharm. 2017 Oct 30;532(1):603-611. doi: 10.1016/j.ijpharm.2017.09.035. Epub 2017 Sep 18.
The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug. The ASDs were characterized by Powder X-Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Solid State Nuclear Magnetic Resonance (ssNMR) and dissolution studies. The data showed that the ASDs were physically and chemically stable at 20°C and 50% RH over 12 months. PXRD results indicated that the ITZ in the ASDs was in the amorphous state and no recrystallization occurred. DSC scans confirmed that each formulation exhibited a single intermediate glass transition (T), around 96.4°C, indicating that ITZ was completely miscible in the polymeric blends of HPMCP and Soluplus at up to 30% (w/w) drug loading and that the two polymers were miscible with each other in the presence of ITZ. The FTIR analysis indicated the formation of strong hydrogen bonding between ITZ, HPMCP and Soluplus. The dissolution end-point of the ASDs was determined to be approximately 10 times greater than that of the crystalline ITZ.
本研究的目的是评估羟丙基甲基纤维素邻苯二甲酸酯（HPMCP-HP-50）和固体分散体聚合物（Soluplus）的新型组合，以提高所制备的无定形固体分散体（ASD）的物理化学稳定性和溶解度。这是通过热熔挤出（HME）实现的，即在三元体系中将结晶活性药物成分（API）转化为更易溶的无定形形式。选择生物药剂学分类系统II类（BCS II）API伊曲康唑（ITZ）作为模型药物。通过粉末X射线衍射（PXRD）、差示扫描量热法（DSC）、热重分析（TGA）、傅里叶变换红外（FTIR）光谱、固态核磁共振（ssNMR）和溶出度研究对ASD进行了表征。数据表明，ASD在20°C和50%相对湿度下12个月内物理和化学性质稳定。PXRD结果表明，ASD中的ITZ处于无定形状态，未发生重结晶。DSC扫描证实，每种制剂在约96.4°C处均表现出单一的中间玻璃化转变（T），表明在高达30%（w/w）的药物载量下，ITZ在HPMCP和Soluplus的聚合物共混物中完全互溶，并且在ITZ存在的情况下，这两种聚合物相互互溶。FTIR分析表明ITZ、HPMCP和Soluplus之间形成了强氢键。ASD的溶出终点确定为结晶ITZ的约10倍。
