Response Surface Methodology to Obtain β-Estradiol Biodegradable Microspheres for Long-Term Therapy of Osteoporosis

Abstract

The purpose of this work was to evaluate the main and interaction effects of formulation factors on the drug encapsulation efficiency of β-estradiol biodegradable microspheres by applying response surface methodology. A secondary purpose was to obtain an optimized formula for long-term therapy of osteoporosis. A three factor, three level Box-Behnken experimental design was used to get 15 experimental runs. The independent variables were drug/polymer ratio (X1), dispersing agent concentration (X2), and deaggregating agent concentration (X3). The dependent variables were percentage encapsulation efficiency (Y1), cumulative percent drug released (Y2), and percentage yield of the microspheres (Y3). The formulations were prepared by emulsion solvent evaporation technique using ethyl acetate as organic solvent. The optimized formulation was maximized for encapsulation efficiency and further characterized for the particle size distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The mathematical relationship obtained between X1, X2, X3, and Y1 was:

Y1 = −129.85 + 29.35X₁ + 129.99X₂ + 64.82X₃ − 3.2X₁X₂ − 0.29X₁X₃ − 35.83X₂X₃ − 2.05X₁² − 13.23X₂² − 5.92X₃² (R2 = 0.99)

The equation showed that X1, X2, and X3 affect Y1 positively but interaction between any two of these factors affects Y1 negatively. The most significant interaction was between X2 and X3. The finding indicated that controlled releases β-estradiol biodegradable microspheres with high encapsulation efficiency and low pulsatile release can be prepared and the quantitative response surface methodology applied helped in understanding the effects and the interaction effects between the three factors applied.

Keywords:

• controlled drug release
• beta-estradiol
• Box-Behnken experimental design
• biodegradable polymers
• optimization