INTRODUCTIONThe objective of this research was to optimize the processing parameters for poly(D,L-lactide-coglycolide) (PLGA) microspheres of 5-fluorouracil (5-FU) and to mathematically relate the process parameters and properties of microspheres. Microspheres were prepared by a water-in-oil-in-water emulsion solvent evaporation technique. A 3 2 factorial design was employed to study the effect of the volume of the internal phase of the primary emulsion and the volume of the external phase of the secondary emulsion on yield, particle size, and encapsulation efficiency of microspheres. An increase in the volume of the internal phase of the primary emulsion resulted in a decrease in yield and encapsulation efficiency and an increase in particle size of microspheres. When the volume of the external phase of the secondary emulsion was increased, a decrease in yield, particle size, and encapsulation efficiency was observed. Microspheres with good batch-to-batch reproducibility could be produced. Scanning electron microscopic study indicated that microspheres existed as aggregates.Poly(D,L-lactide-co-glycolide) (PLGA) is a biocompatible, bioabsorbable, and biodegradable polymer that is used to formulate many types of implantable and injectable drug delivery systems for humans and other animals. PLGA microspheres have been reported as carriers for site-specific delivery of various drugs like adapalene 1 and tetracycline.
2In the present study, an attempt was made to prepare PLGA microspheres of 5-fluorouracil (5-FU) for sitespecific delivery of 5-FU through passive targeting. The pyrimidine analogue 5-FU is an antimetabolite and immunosuppressive agent. It is used in the treatment of breast, colon, stomach, pancreas, ovary, head and neck, urinary bladder and lung cancer. 3 It has a rapid plasma clearance and a short half-life (t 1/2 :10-20 minutes). The drug can be encapsulated in microspheres to prolong its residence time and thereby its action.The 5-FU is water soluble. Several reports are available for encapsulation of hydrophilic drugs into PLGA microspheres by a water-in-oil-in-water (w/o/w) emulsification solvent evaporation technique.4,5 Hence, we prepared PLGA microspheres containing 5-FU by this technique. We could prepare microspheres with good batch to batch reproducibility.
KEYWORDS: 5-fluorouracil, microspheres, PLGA microspheres, optimizationSeveral researchers have tried to study the effect of process parameters on properties of microspheres and to derive mathematical models that can be used to predict process kinetics. Sato et al 6 reported that the sphericity, size, and yield of microspheres were influenced by the preparation procedure, surfactant type and concentration, temperature of the continuous phase, polymer concentration in the dispersed phase, and ratio of marker to polymer. Jeyanthi et al 2 have shown the effect of the solvent removal technique, the dispersed phase composition, and the ratio of dispersed to continuous phase volume (D/C ratio) on matrix character-
