ABSTRACT
This case study describes in vitro and in vivo characterization performed to support manufacturing scale-up, from laboratory to pilot scale, of an experimental microsphere formulation.
The experimental formulation consists of an active pseudo-decapeptide encapsulated in a poly(lactide-co-glycolide) matrix at a target loading of approximately 8% w=w. Microspheres were manufactured in a continuous manner by a proprietary process (1) involving the formation of an oil-in-water emulsion, extraction of the organic phase, drying and collection of microspheres in the size range 25-125mm. Mannitol is
added to the extraction phase to facilitate subsequent handling. Three formulation variants, based on polymers differing in lactide:glycolide ratio and molecular weight distribution, were investigated in pre-clinical studies and in vivo and in vitro release characteristics were determined. A preliminary in vitro-in vivo correlation was developed for using a rat model, supporting the use of the in vitro release test to select batches for pre-clinical use.
