Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 45, Issue 1-2, Pages 8-18Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2011.10.016
Keywords
Mesoporous silica MCM-41 nanoparticles; Anticancer drug; Methotrexate; Loading; Factorial design
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The aim of this study was to develop methotrexate loaded mesoporous MCM-41 nanoparticles for improved dissolution of methotrexate. The mesoporous MCM-41 nanoparticles act as carrier for drug and increase the solubility of the drug. In order to achieve this objective small pore size MCM-41 nanoparticles have been synthesized followed by drug loading process. The process of drug loading was optimized using full 3(3) factorial design. With a view to obtain maximum drug loading three variables, concentration of drug solution, stirring rate, and drug:carrier ratio were optimized using a full 3(3) factorial design. Using statistically designed experiments, the inclusion of methotrexate in MCM-41 nanoparticles was successfully carried out to obtain a drug loading of about 48%. X-ray powder diffraction and differential scanning calorimetry revealed the presence of methotrexate in amorphous form and FT-IR spectroscopy showed the presence of light interactions between the silicate silanols and the drug. The decrease of Brunauer, Emmett and Teller specific surface area and pore volume between free MCM-41 and the inclusion compound was the proof of the presence of methotrexate inside the mesopores. The inclusion compound was submitted to in vitro dissolution tests and a remarkable dissolution rate improvement was observed in comparison to the crystalline drug in all tested conditions. (C) 2011 Elsevier B.V. All rights reserved.
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