Factorial effect of process parameters on pharmaceutical characteristics of biodegradable PLGA microparticles

Among the drug delivery strategies intended to increase the bioavailability of drugs, the use of polymeric biodegradable microcarriers has shown a significant degree of success.The purpose of this study was developing a polymeric drug delivery system for a model drug: furosemide, which belongs to class IV of BCS (low solubility and low permeability), intended to oral administration and improving the stability and intestinal absorption of the drug.To achieve this goal, furosemide loaded poly (lactic-co-glycolic acid) (PLGA) microparticles were prepared by solvent evaporation method and characterized. To obtain an appropriate mathematical model with minimum experiments for optimization of formulation, a 24 full factorial design based on four independent variables (amount of polymer, emulsifier, volume of internal and external phases) was used to plan the experiments. The effects of these parameters on the drug loading efficiency were investigated. The release profiles of furosemide from microparticles were examined in simulated gastric fluid (SGF pH 1.2), simulated intestinal fluid (SIF pH 7.4) and phosphate buffer (pH: 7.4).The results of optimized formulation showed a narrow size distribution with an average diameter of 60 ± 5 μm and a drug loading of more than 60%. In simulated gastric fluid (SGF), less than 8% of furosemide was released from microparticles in 24 h and about 60% and 50% furosemide was released in 24 h in simulated intestinal fluid (SIF) and phosphate buffer, respectively.Results from this preliminary work showed that furosemide loaded PLGA microparticles can be successfully obtained through solvent-evaporation technique, with good morphological characteristics, high encapsulation efficiency and controlled drug release profile suitable for per oral administration.Keywords: Furosemide; PLGA microparticles; Full factorial design

Factorial effect of process parameters on pharmaceutical characteristics of biodegradable PLGA microparticles

Among the drug delivery strategies intended to increase the bioavailability of drugs, the use of polymeric biodegradable microcarriers has shown a significant degree of success.The purpose of this study was developing a polymeric drug delivery system for a model drug: furosemide, which belongs to class IV of BCS (low solubility and low permeability), intended to oral administration and improving the stability and intestinal absorption of the drug.To achieve this goal, furosemide loaded poly (lactic-co-glycolic acid) (PLGA) microparticles were prepared by solvent evaporation method and characterized. To obtain an appropriate mathematical model with minimum experiments for optimization of formulation, a 24 full factorial design based on four independent variables (amount of polymer, emulsifier, volume of internal and external phases) was used to plan the experiments. The effects of these parameters on the drug loading efficiency were investigated. The release profiles of furosemide from microparticles were examined in simulated gastric fluid (SGF pH 1.2), simulated intestinal fluid (SIF pH 7.4) and phosphate buffer (pH: 7.4).The results of optimized formulation showed a narrow size distribution with an average diameter of 60 ± 5 μm and a drug loading of more than 60%. In simulated gastric fluid (SGF), less than 8% of furosemide was released from microparticles in 24 h and about 60% and 50% furosemide was released in 24 h in simulated intestinal fluid (SIF) and phosphate buffer, respectively.Results from this preliminary work showed that furosemide loaded PLGA microparticles can be successfully obtained through solvent-evaporation technique, with good morphological characteristics, high encapsulation efficiency and controlled drug release profile suitable for per oral administration.Keywords: Furosemide; PLGA microparticles; Full factorial design