Preparation and evaluation of a self-emulsifying drug delivery system of etoposide-phospholipid complex.
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY(2011)
Abstract
Aim: 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.
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Key words
Bioavailability,etoposide,phospholipid complex,self-emulsifying drug delivery system
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