title: Preparation and evaluation of a self-emulsifying drug delivery system of etoposide-phospholipid complex.
abstract: OBJECTIVE
  The aim of this study was to develop a new phospholipid complex self-emulsifying drug delivery system (PC-SEDDS) to enhance bioavailability of oral etoposide, a drug with poor water solubility.
  
  
  METHODS
  Etoposide-phospholipid complex (EPC) was prepared by reacting etoposide and phospholipid in tetrahydrofuran and confirmed as a phospholipid compound by differential scanning calorimetry (DSC). Solubility of EPC and etoposide was determined in various vehicles. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsification region of EPC-SEDDS, and the effects of oil concentration, drug loading, and aqueous media on droplet size were investigated.
  
  
  RESULTS
  The optimal formulation of EPC-SEDDS was EPC:octyl and decyl monoglyceride (ODO):Cremopher EL:PEG-400 (1:20:48:32) (w/w/w/w). Compared with etoposide-phospholipid complex suspension (EPCS) and etoposide suspension (ES), cumulative release of etoposide from EPC-SEDDS increased by 1.31 and 2.65 fold at 24 hours, respectively. Compared with ES, relative bioavailability of EPC-SEDDS, E-SEDDS, and EPCS after oral administration in rats was enhanced by 60.21-, 44.9-, and 8.44- fold, respectively.
  
  
  CONCLUSIONS
  The synergistic effect between PC and SEDDS contributed to the enhanced bioavailability of etoposide. It was concluded that PC-SEDDS proved to be a potential system for delivering orally administered hydrophobic compounds including etoposide.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, PR China.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Wu
authors.forename: Dan
authors.initials: D
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Yang
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D004357:Drug Synergism; D045703:Emulsifying Agents / Q000737:chemistry* / Q000494:pharmacology; D004655:Emulsions / Q000737:chemistry; D005047:Etoposide / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005663:Furans / Q000737:chemistry; D008297:Male; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010743:Phospholipids / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D005663:Furans; D009821:Oils; D010743:Phospholipids; D013535:Suspensions; C018674:tetrahydrofuran; D005047:Etoposide