Optimisation of aciclovir poly(D,L-lactide-co-glycolide) microspheres for intravitreal administration using a factorial design study

Abstract

The purpose of this work was to obtain an optimised long-term aciclovir PLGA microspheres formulation for intravitreal administration to minimise, as much as possible, the dose of microspheres to be administered with a suitable particle size for its injection through a 27G needle in a single dose. Microspheres were prepared by the solvent evaporation method. To obtain the optimum formulation a two-factor five-level central rotatable composite 2(2) + star design was employed. The independent variables were aciclovir and gelatin (added to the external phase of the emulsion). The dependent variables were the yield of production (%), the encapsulation efficiency (%), the initial burst release (%), the cumulative amount released from 1 to 14 days and the amount of aciclovir at the end of the release assay (microg aciclovir/mg microspheres). The best formulation according to the studied variables was (0,0), prepared with 80 mg of aciclovir and 80 mg of gelatin. This formulation showed good yield of production (70.14 +/- 3.72 %) and encapsulation efficiency ( 70.77 +/- 2.62 %), and released the drug at a constant rate for 63 days with a mean release constant of 1.73 +/- 0.08 microg/day per mg microspheres. The selected formulation reduces a 40% the dose of microspheres to be administered through a 27G needle with respect to previous studies.