Chun Tao: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Juming Chen: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China; College of Pharmacy, Fujian Medical University, Fuzhou 350108, PR China.
Aiwen Huang: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Jing Zhang: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Bing Lin: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Zhihong Liu: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Minxin Zhang: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Xu Chen: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Lingjun Zeng: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Lingna Zhang: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
Hongtao Song: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China. Electronic address: sohoto@vip.163.com.
The application of sirolimus (SRL) as immunosuppressive agent is hampered by its poor water solubility and narrow therapeutic range. The self-microemulsifying drug delivery system (SMEDDS) succeeded in improving the solubility of SRL in our previous work. In this study, the formulation of the SMEDDS was further optimized by investigating the influence of the excipients including the media, antioxidant and organic acid. It was demonstrated that addition of 0.20% of citric acid in SMEDDS most efficiently promoted the stability of SRL under high temperature (40±2°C), high humidity (relative humidity 90±5%) or strong light irradiation (4500±500lx). SMEDDS absorbed by microcrystalline cellulose (MCC) was mixed with hydroxypropyl methylcellulose (HPMC) to prepare tablets. The optimal formulation composed of 15% of HPMC 100 LV with hardness of 120N, which had a sustained release of 12h. Results of X-ray powder diffraction and differential scanning calorimetry demonstrated that SRL in the tablets was in amorphous or molecularly dispersed state. The SMEDDS-tablets presented as promising substrates for water insoluble drugs with enhanced stability and extended release.
