M Anjana, Gogate Parag R
Department of Chemical Engineering, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, India.
Heliyon. 2024 Mar 18;10(6):e28205. doi: 10.1016/j.heliyon.2024.e28205. eCollection 2024 Mar 30.
Metformin Hydrochloride (MH), an orally administered antidiabetic drug from the biguanide family, encounters issues of wide particle size distribution, inefficient dissolution rates and short half-life leading to excess dosage which can result in lactic acidosis. Novel approaches that yield smaller particle size and uniform distribution at higher yields are significant to tackle problems associated with solubility and optimum dosage levels of the administered drugs. In the current research related to microsphere synthesis, a controlled process based on pressure and ultrasonic nozzles for the atomization of liquid, was applied with an objective of optimizing particle size of microspheres of MH in sodium alginate, a biopolymer excipient matrix. The study carried out in spray dryer elucidated parameter optimization using one variable at a time approach by varying important parameters as inlet temperature of air (120°C-150 °C), rate of flow of feed (1.5 mL/min-3 mL/min), aspirator rate (800 rpm-1400 rpm) and polymer content in feed solution (1 g-8 g) using ultrasonic and pressure nozzles for comparison with the target output parameter as particle size and yield. While the particle size at optimum conditions were <10 μm for both types of atomization, ultrasound assisted spray drying exhibited narrower distribution compared to the pressure atomization. Particle characterization performed using SEM, optical microscopy, FTIR, XRD and DSC revealed slight deformation with no chemical interaction and slight decrease in crystalline nature of pure drug. Overall, an improved process based on the use of ultrasound with optimized parameters has been demonstrated for synthesis of MH containing microspheres.
盐酸二甲双胍（MH）是一种口服的双胍类抗糖尿病药物，存在粒径分布广、溶解效率低和半衰期短等问题，导致用药过量，可能引发乳酸性酸中毒。采用新方法以更高产率生成更小粒径且分布均匀的颗粒，对于解决与所给药药物的溶解度和最佳剂量水平相关的问题具有重要意义。在当前有关微球合成的研究中，应用了一种基于压力和超声喷嘴的液体雾化控制工艺，目的是优化海藻酸钠（一种生物聚合物辅料基质）中MH微球的粒径。在喷雾干燥器中进行的研究通过一次改变一个变量的方法来优化参数，改变的重要参数包括空气入口温度（120°C - 150°C）、进料流速（1.5 mL/min - 3 mL/min）、吸气速率（800 rpm - 1400 rpm）以及进料溶液中的聚合物含量（1 g - 8 g），使用超声喷嘴和压力喷嘴进行比较，目标输出参数为粒径和产率。虽然在两种雾化方式的最佳条件下粒径均<10μm，但与压力雾化相比，超声辅助喷雾干燥的粒径分布更窄。使用扫描电子显微镜（SEM）、光学显微镜、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）和差示扫描量热法（DSC）进行的颗粒表征显示，纯药物有轻微变形，无化学相互作用，结晶性质略有下降。总体而言，已证明基于使用超声并优化参数的改进工艺可用于合成含MH的微球。
