Poly(D,L-Lactide-Co-Glycolide) microspheres containing 5-fluorouracil: Optimization of process parameters

Abstract

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-

Preparation, Characterization, and Pharmacodynamics of Exenatide-Loaded Poly(DL-lactic-co-glycolic acid) Microspheres

“…Parikh et al also reported the similar results. 19) PLGA concentration in the oil phase is also a key factor influencing the encapsulation efficiency of exenatide microspheres. Exenatide microspheres were prepared using PLGA by varying concentration as given in Table 1 (Formulation F, A and G).…”

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters

“…However, it has been shown that the a high encapsulation efficiency of macromolecular hydrophilic compounds (e.g. peptides, proteins, DNA) in PLGA microspheres can be established by optimizing the formulation parameters, such as type and polymer concentration [10], type and concentration of surfactant [11,12], volume of the internal phase of the primary emulsion, and the volume of the external phase of the secondary emulsion [13]. There are several drawbacks associated with the use of PLGA as a drug delivery system.…”

Investigation on Processing Variables for the Preparation of Fluconazole-Loaded Ethyl Cellulose Microspheres by Modified Multiple Emulsion Technique

“…Unlike w/o emulsification method, water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique proves much more effective when the aqueous solubility of drug is high (>900 mg/ml) and partitioning into the organic phase is disfavorable (6). Accordingly, microspheres containing water soluble drugs have been prepared using different polymers such as poly(lactide-co-glycolide) (PLGA) (7), eudragit RS (8), polymethyl methacrylate (9). In addition, modified procedures of this technique have been proposed to obtain desired properties of the microspheres, loaded with the water soluble active principles.…”