Fluphenazine release from biodegradable microparticles: characterization and modelling of release.
The release of actives encapsulated in biodegradable poly-lactide-co-glycolide (PLGA)-based microparticles may be diffusion controlled, dependent on polymer degradation, or may occur by a combination of drug diffusion and polymer degradation. This report applies a model, describing combined diffusional and polymer degradation-assisted drug release, to quantify the release of fluphenazine HCl (F-HCl) from PLGA microspheres. Parameters for the release process showed that both the initial drug release phase and the polymer controlled drug release phase were dependent on the F-HCl loading of the microspheres. The percentage drug released in the burst phase and the length of the lag phase were dependent on F-HCl loading. In the degradation controlled release phase, drug release was faster the higher the loading, as shown by the decrease in t(max) from 27 to 10 days, as F-HCl loadings increased from 4.2 to 16.6%w/w. The presence of F-HCl was found to catalyse the degradation of PLGA polymer during particle manufacture and during dissolution. When compared to drug free microspheres, F-HCl accelerated PLGA degradation as shown by the approximately 5-fold increase in both PLGA degradation rate constant (k) and reduction in t(max).
Dunne
Margaret M
MM
School of Pharmacy and Pharmaceutical Sciences, University of Dublin, Trinity College, Dublin 2, Ireland.
Ramtoola
Zebunnissa
Z
Corrigan
Owen I
OI
D001672:Biocompatible Materials / Q000737:chemistry; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations; D004058:Diffusion; D005476:Fluphenazine / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D008956:Models, Chemical; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013997:Time Factors
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005476:Fluphenazine