Mechanistic explanation of the (up to) 3 release phases of PLGA microparticles: Diprophylline dispersions

Publication date: Available online 11 November 2019Source: International Journal of PharmaceuticsAuthor(s): F. Tamani, C. Bassand, M. Hamoudi-Ben Yelles, F. Danede, J.F. Willart, F. Siepmann, J. SiepmannAbstractThe aim of this study was to better understand the root causes for the (up to) 3 drug release phases observed with poly (lactic-co-glycolic acid) (PLGA) microparticles containing diprophylline particles: The 1st release phase (“burst release”), 2nd release phase (with an “about constant release rate”) and 3rd release phase (which is again rapid and leads to complete drug exhaust). The behavior of single microparticles was monitored upon exposure to phosphate buffer pH 7.4, in particular with respect to their drug release and swelling behaviors. Diprophylline-loaded PLGA microparticles were prepared with a solid-in-oil-in-water solvent extraction/evaporation method. Tiny drug crystals were rather homogeneously distributed throughout the polymer matrix after manufacturing. Batches with “small” (63 µm), “medium-sized” (113 µm) and “large” (296 µm) microparticles with a practical drug loading of 5-7 % were prepared. Importantly, each microparticle releases the drug “in its own way”, depending on the exact distribution of the tiny drug crystals within the system. During the burst release, drug crystals with direct surface access rapidly dissolve. During the 2nd release phase tiny drug crystals (often) located in surface near regions which undergo ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research