A lyophilized etoposide submicron emulsion with a high drug loading for intravenous injection: preparation, evaluation, and pharmacokinetics in rats
- 5 November 2010
- journal article
- research article
- Published by Informa UK Limited in Drug Development and Industrial Pharmacy
- Vol. 36 (12), 1444-1453
- https://doi.org/10.3109/03639045.2010.487267
Abstract
Objective: To develop a submicron emulsion for etoposide with a high drug loading capacity using a drug–phospholipid complex combined with drug freeze-drying techniques. Methods: An etoposide–phospholipid complex (EPC) was prepared and its structure was confirmed by X-ray diffraction and differential scanning calorimetry analysis. A freeze-drying technique was used to produce lyophilized etoposide emulsions (LEPE), and LEPE was investigated with regard to their appearance, particle size, and zeta potential. The pharmacokinetic study in vivo was determined by the UPLC/MS/MS system. Results: It showed that EPC significantly improved the liposolubility of etoposide, indicating a high drug loading intravenous emulsion could be easily prepared by EPC. Moreover, the obtained loading of etoposide in the submicron emulsion was 3.0 mg/mL, which was three times higher than that of the previous liquid emulsions. The optimum cryoprotectant was trehalose (15%) in freeze-drying test. The median diameter, polydispersity index, and zeta potential of the optimum formulation of LEPE were 226.1 ± 5.1 nm, 0.107 ± 0.011, and −36.20 ± 1.13 mV, respectively. In addition, these parameters had no significant change during 6 months storage at 4 ± 2°C. The main pharmacokinetic parameters exhibited no significant differences between LEPE and etoposide commercial solution except for area under the concentration–time curve and clearance. Conclusions: The stable etoposide emulsion with a high drug loading was successfully prepared, indicating the amount of excipients such as the oil phase and emulsifiers significantly decreased following administration of the same dose of drug, effectively reducing the metabolism by patients while increasing their compliance. Therefore, LEPE has a great potential for clinical applications.Keywords
This publication has 24 references indexed in Scilit:
- Chemical Stability of Teniposide in Aqueous and Parenteral Lipid EmulsionsDrug Development and Industrial Pharmacy, 2009
- Preparation and Characterization of a Submicron Lipid Emulsion of Docetaxel: Submicron Lipid Emulsion of DocetaxelDrug Development and Industrial Pharmacy, 2008
- Etoposide: four decades of development of a topoisomerase II inhibitorEuropean Journal Of Cancer, 1998
- Plasma Compatibility of Injectables: Comparison of Intravenous U-74006F, a 21-Aminosteroid Antioxidant, with Dilantin Brand of Parenteral PhenytoinJournal of Pharmaceutical Sciences, 1991
- A phase II study of oral etoposide in elderly patients with small cell lung cancer.Thorax, 1989
- Preformulation Study of Etoposide: Identification of Physicochemical Characteristics Responsible for the Low and Erratic Oral Bioavailability of EtoposidePharmaceutical Research, 1989
- Degradation kinetics of etoposide in aqueous solutionInternational Journal of Pharmaceutics, 1988
- The Clinical Pharmacology of Etoposide and TeniposideClinical Pharmacokinetics, 1987
- Etoposide (VP-16–213)New England Journal of Medicine, 1985
- Etoposide (VP-16-213)Cancer Treatment Reviews, 1979