Effect of processing parameters on characteristics of biodegradable extended-release microspheres containing leuprolide acetate.

Abstract

Objective: Poly(lactic-co-glycolic acid) microsphere containing leuprolide acetate - an extended-release drug delivery system whose characteristics (i.e. loading capacity, particle size and initial burst phase) depend on processing parameters.

Methods: Microspheres were prepared by water/oil/water double-emulsion solvent evaporation method; drug content in microspheres was determined by high-performance liquid chromatography (HPLC); peptide concentration in the release medium was measured by fluorescence spectrometer; particle size and particle size distribution were measured by laser diffraction method; interaction between poly(lactic-co-glycolic acid) (PLGA) and leuprolide acetate (LA) was determined by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR).

Results: DSC curves and assay results proved LA adsorption ability of PLGA film. FTIR spectra proved ionic interactions between positive charged LA molecules and negative charged PLGA chains in phosphate buffer pH 7.4. Ten processing parameters including LA concentration (mg/mL), PLGA concentration (mg/mL), W1/O ratio (v/v), the first homogenization time (min), the first homogenization speed (rpm), O/W2 ratio (v/v), PVA concentration of W2 phase (mg/ml), the second homogenization time (s), the volume of diluted solution (ml) and nitrogen aeration time (min) have impacts on loading capacity, particle size and initial burst phase of microspheres. The release exponent (n) of Korsmeyer-Peppas model was 0.3571 (lower than 0.43), indicating that Fickian diffusion manipulated release kinetics of initial burst phase.

Conclusions: Processing parameter modification contributes to small microspheres with high loading capacity and controlled initial burst phase.