Optimisation of aciclovir poly(D,L-lactide-co-glycolide) microspheres for intravitreal administration using a factorial design study.
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.
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
C
C
Martínez-Sancho
R
R
Herrero-Vanrell
S
S
Negro
D000212:Acyclovir / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D004655:Emulsions; D005780:Gelatin / Q000737:chemistry; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012107:Research Design; D012995:Solubility
D000998:Antiviral Agents; D004655:Emulsions; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin; D000212:Acyclovir