Study on Enhanced Dissolution of Azilsartan-Loaded Solid Dispersion, Prepared by Combining Wet Milling and Spray-Drying Technologies

• Published in: AAPS PharmSciTech Vol. 18; no. 2; pp. 473 - 480
• Main Authors: Lu, Tianshu, Sun, Yinghua, Ding, Dawei, Zhang, Qi, Fan, Rui, He, Zhonggui, Wang, Jing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2017
• Subjects: Benzimidazoles - chemistry; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning - methods; Cellulose - analogs & derivatives; Cellulose - chemistry; Chemistry, Pharmaceutical - methods; Microscopy, Electron, Scanning - methods; Oxadiazoles - chemistry; Particle Size; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Powders - chemistry; Research Article; Solubility; Spectroscopy, Fourier Transform Infrared - methods; Tablets - chemistry; Technology, Pharmaceutical - methods; Viscosity; Water - chemistry; X-Ray Diffraction - methods; dissolution rate; solid dispersion; wet milling; azilsartan; spray-drying
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-016-0531-1

The purpose of this study was to develop a combination method of wet milling and spray-drying technologies to prepare the solid dispersion and improve the dissolution rate of poorly water-soluble drug candidates. Azilsartan (AZL) was selected as the model drug for its poor water solubility. In the study, AZL-loaded solid dispersion was prepared with polyethylene glycol 6000 (PEG6000) and hydroxypropyl cellulose with super low viscosity (HPC-SL) as stabilizers by using combination of wet grinding and spray-drying methods. The high AZL loading solid dispersion was then characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Besides, dissolution test was carried out by the paddle method and stability investigation was also conducted. As a result, the dissolution rate of the solid dispersion tablets was found to be greater than conventional tablets, but in close agreement with market tablets. Furthermore, the formulation was shown to be stable at 40 ± 2°C and 75 ± 5% for at least 6 months, owing to its decreased particle size, morphology, and its crystal form. It was concluded that the combination of wet milling and spray-drying approaches to prepare solid dispersion would be a prospective method to improve the dissolution rate of poorly water-soluble drugs.