Improved synthesis of metformin hydrochloride-sodium alginate (MH-NaALG) microspheres using ultrasonic spray drying

Abstract

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.

Keywords

• Ultrasonic atomization
• Pressure atomization
• Microspheres
• Spray drying
• Operating parameters