Srinivasan Priyanka, Almutairi Mashan, Dumpa Nagireddy, Sarabu Sandeep, Bandari Suresh, Zhang Feng, Ashour Eman, Repka Michael A
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.
College of Pharmacy, The University of Texas at Austin, TX, 78712, USA.
J Drug Deliv Sci Technol. 2021 Feb;61. doi: 10.1016/j.jddst.2020.102128. Epub 2020 Oct 6.
The objective of the current study was to develop theophylline (TPH) nicotinamide (NAM) pharmaceutical co-crystals using the hot melt extrusion (HME) technology and evaluate the processability of the co-crystals using different polymeric carriers. A physical mixture of 1:1 M ratio of TPH and NAM was employed to prepare the co-crystals. Hydroxypropylmethylcellulose acetate succinate, polyethylene oxide, and Kollidon® VA-64 (5% w/w) were investigated as polymeric carriers for the HME process. Solid-state characterization using differential scanning calorimetry showed two endothermal peaks, one at 126.4 °C indicating eutectic formation and another at 174 °C indicating the melting point of the co-crystal for all formulations, except the Kollidon® VA-64 extrudates, which showed a single peak at 174 °C. Fourier-transform infrared spectroscopy and powder X-ray diffraction studies revealed the formation of co-crystals. The feasibility to formulate the extrudates into solid dosage forms was assessed by formulating a tablet blend. The three-month stability studies showed no degradation at the accelerated stability conditions of 40 (±2) ° C and 75 (±5) % RH. Finally, the results demonstrated that the presence of mixing zones in screw configuration and extrusion temperature are critical processing parameters that influence co-crystal formation.
本研究的目的是利用热熔挤出（HME）技术制备茶碱（TPH）-烟酰胺（NAM）药物共晶体，并使用不同的聚合物载体评估共晶体的可加工性。采用TPH与NAM摩尔比为1:1的物理混合物来制备共晶体。研究了羟丙基甲基纤维素琥珀酸酯、聚环氧乙烷和共聚维酮VA-64（5%w/w）作为HME工艺的聚合物载体。差示扫描量热法进行的固态表征显示有两个吸热峰，一个在126.4℃，表明形成了低共熔物，另一个在174℃，表明所有制剂共晶体的熔点，但共聚维酮VA-64挤出物除外，其在174℃显示一个单峰。傅里叶变换红外光谱和粉末X射线衍射研究表明形成了共晶体。通过制备片剂混合物评估了将挤出物制成固体剂型的可行性。为期三个月的稳定性研究表明，在40（±2）℃和75（±5）%相对湿度的加速稳定性条件下没有降解。最后，结果表明螺杆配置中的混合区和挤出温度是影响共晶体形成的关键加工参数。
