title: Development of solidified self-microemulsifying delivery systems with enhanced stability of sirolimus and extended release.
abstract: 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.
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Tao
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China; College of Pharmacy, Fujian Medical University, Fuzhou 350108, PR China.
authors.forename: Juming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Minxin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China.
authors.forename: Lingna
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350025, PR China. Electronic address: sohoto@vip.163.com.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Song
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D019343:Citric Acid / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000737:chemistry*; D033362:Powder Diffraction; D020123:Sirolimus / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D000975:Antioxidants; D003692:Delayed-Action Preparations; D004655:Emulsions; D007166:Immunosuppressive Agents; D013607:Tablets; D019343:Citric Acid; D020123:Sirolimus
keywords: Extended release; Self-microemulsifying drug delivery system; Sirolimus; Stability; Tablet