IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
DEVELOPMENT AND CHARACTERIZATION OF AN INNOVATIVE TAMOXIFEN
Autor/es:
EZEQUIEL MONTEAGUDO; YAMILA GÁNDOLA; GONZÁLEZ LORENA; ARIANA CARLUCCI
Lugar:
Córdoba, Argentina
Reunión:
Congreso; 1ª Reunión Internacional de Ciencias Farmacéuticas; 2010
Institución organizadora:
Faultad de Ciencias Bioquímicas y Farmacéuticas, Universidad de Rosario
Resumen:
DEVELOPMET AD CHARACTERIZATIO OF A IOVATIVE TAMOXIFE
MICROEMULSIO
Ezequiel Monteagudoa* , Yamila Gandolab, Lorena Gonzalezb, Adriana Carlucciaa* , Yamila Gandolab, Lorena Gonzalezb, Adriana Carluccia
a Department of Pharmaceutical Technology - b Department of Biological Chemistry
Faculty of Pharmacy and Biochemistry, University of Buenos Aires - Junin 956, (1113) Buenos Aires
Argentina
Faculty of Pharmacy and Biochemistry, University of Buenos Aires - Junin 956, (1113) Buenos Aires
Argentina
Faculty of Pharmacy and Biochemistry, University of Buenos Aires - Junin 956, (1113) Buenos Aires
Argentina
Department of Pharmaceutical Technology - b Department of Biological Chemistry
Faculty of Pharmacy and Biochemistry, University of Buenos Aires - Junin 956, (1113) Buenos Aires
Argentina
Introduction
Breast cancer is the most common cancer among women and the second leading cause of disease deaths.
Tamoxifen (TMX) is the drug of first election in premenopausal patients with estrogen receptor (+) (1). It
shows poor water solubility and vulnerability to enzymatic degradation in intestine and liver (2). Its oral
bioavailability is affected by the first pass effect (3). The objective of the work was to optimize and
characterize a microemulsion containing TMX that could present a high solubilization capacity and a low
in vitro toxicity profile.toxicity profile.
Materials and methods
Screening of the microemulsion region was performed using the titration method at 37°C (4). Polisorbate
80 and other pharmaceutically acceptable excipients were chosen; compositions were then represented in
Pseudo Ternary Diagrams. To determine the equilibrium solubility of the drug in formulations, excess of
drug was added to the formulations, they were left to equilibrate for 72 hs, filtered and finally analyzed by
HPLC (Shimadzu, Japan). Droplet size was evaluated using a Nanozetasizer, Malvern Instruments, UK
(37°C). Citotoxicity evaluation of the microemulsions and excipients were carried out using MCF-7
breast cancer cell line. The selected compositions diluted with culture media were incubated 48 hs and
finally viable cells were determined using CellTiter 96R Non-Radioactive Cell Proliferation Assay
(MTS).
finally viable cells were determined using CellTiter 96R Non-Radioactive Cell Proliferation Assay
(MTS).
finally viable cells were determined using CellTiter 96R Non-Radioactive Cell Proliferation Assay
(MTS).
. The selected compositions diluted with culture media were incubated 48 hs and
finally viable cells were determined using CellTiter 96R Non-Radioactive Cell Proliferation Assay
(MTS).
Results.
Considering solubility and citotoxicity assays, phosphatidylcholine was selected as oil phase and ethanol
and popylenglycol as cosurfactants. During the screening, only formulations containing ethanol were able
to form microemulsions at the desired excipients levels. Finally, 5 different compositions were selected
for physicochemical characterization. Solubility studies showed an improvement of drug solubilization of
10000 fold compared with water. Polisorbate 80 was the excipient with the highest rate of toxicity but the
dilutions used were the usual ones.
Discussions/conclusions.
Microemulsions are thermodynamically stable dosage forms, widely accepted that can improve oral
bioavailability or can achieve the desired dose at the tumor site for a longer period. The formulations
prepared and characterized in this work showed a high solubilization capacity and a low toxicity profile,
allowing different anti cancer strategies to be challenged in vitro.in vitro.
Acknowledgments
Financial support was obtained from PICT 2007-00595.
References.
1. Morris P.G., McArthur H.L., Hudis C.A. Therapeutic options for metastatic breast cancer
Expert Opin. Pharmacother. 2009; 10: 967-81.
2. Elnaggar YSR, El-Massik MA, Abadia OY. Self-nanoemulsifying drug delivery systems of
tamoxifen citrate: Design and Optimization. Int. J. Pharm 2009; 380:133141.
3. Shin S, Choi J, Li X. Enhanced bioavailability of tamoxifen after oral administration of
tamoxifen with quercetin in rats. Int. J. Pharm 2006; 313:144149.
4. Kawakami K, et al. Microemulsion formulation for enhanced absorption of poorly soluble
drugs: I. Prescription design. J. Control Rel. 2002; 81:6574.
Corresponding author. Tel +54 11 47048504, fax +54 11 47048545.
e-mail: ezequiel.monteagudo@gmail.com