Tianxiang Chen¹, Quanzhu Yang¹, Yongjian Yang¹, Yingshu Feng², Caleb Kesse Firempong³, Xin Zhang¹, Haibing He⁴, Jingwei Jin¹ , Hongfei Liu^1,3,5

Abstract

Purpose: To prepare azithromycin (AZI) sustained-release suspension containing AZI-coated microcapsules (AZI-CM) impregnated with AZI-drug resin complex (AZI-DRC), in order to mask the bitter taste of AZI and improve the oral compliance of patients. Methods: The AZI-DRC was prepared using the bath method, with cation exchanger resin Amberlite®IRP64 as a drug carrier, and it was characterized using scanning electron microscopy (SEM), x-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Pretreated AZI-DRC was coated using emulsification-solvent evaporation method to achieve sustained-release effect. The effect of coating on in vitro drug release of the microcapsules was investigated to obtain the optimal AZI-CM through single-factor investigation. The optimized AZI-CM formulation was further dispersed in the optimized suspension matrix to obtain AZI sustained-release suspension. Then, the pharmacokinetics of AZI sustained release from the suspension was studied in rats and compared with commercially available AZI dry suspension. Results: Taste evaluation by volunteers showed that AZI-DRC had a good taste-masking effect on AZI. Results from SEM, XRD and FTIR demonstrated that AZI was present in AZI-DRC solely in amorphous form. Three batches of AZI-CM prepared after optimization produced a significant sustained release effect (p < 0.05). The AZI sustained-release suspension did not change significantly after 10 days and 3 months, indicating good stability (F > 0.9; drug release: f2 > 50; drug leakage < 0.5 %). In vivo results showed that AZI sustained-release suspension had a lower Cmax a higher Tmax and a better bioequivalence than AZI dry suspension available in the market. Conclusion: These findings depict a newly developed AZI sustained-release suspension with improved bioavailability, sustained-release effect, masked bitterness, and good therapeutic effect.