title: Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.
abstract: The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200.
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Xuechao
authors: X
authors: Li
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Huanhuan
authors: H
authors: Peng
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Bin
authors: B
authors: Tian
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Jingxin
authors: J
authors: Gou
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Qing
authors: Q
authors: Yao
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Xiaoguang
authors: X
authors: Tao
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Haibing
authors: H
authors: He
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors: Xing
authors: X
authors: Tang
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: bbpharmcai@sina.com.
authors: Cuifang
authors: C
authors: Cai
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D017963:Azithromycin / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D012822:Silicon Dioxide; D017963:Azithromycin
keywords: Aerosil 200; Ball milling; Hot-melt extrusion; Physical stability; Solid dispersion