5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

Abstract

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47 ± 11 and 67 ± 12 µg 5-FU mg⁻¹ microspheres and the percentage of entrapment efficiency was between 52 ± 12 and 74 ± 13. Microspheres were of small size (average diameter: 0.9 ± 0.4–1.4 ± 0.8 µm microspheres without drug; 1.1 ± 0.5–1.7 ± 0.9 µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129 h) was in the order PLA > PLGA 75/25 > PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52 ± 0.82–1.46 ± 0.26 µg 5-FU h⁻¹ per milligram of microspheres) up to 8 or 13 h, depending on the polymer, was obtained.

Keywords: :

• 5-Fluorouracil
• poly(D,L-lactide)
• poly(lactide-co-glycolide)
• microspheres
• controlled release
• spray-dryer