Conversion of PLGA nanoparticle suspensions into solid dosage forms via fluid bed granulation and tableting

Incorporating poorly soluble drugs into polymeric nanoparticles is a widely investigated approach to improve their biopharmaceutical performance. Poly(DL-lactide-co-glycolide) (PLGA) nanoparticle formulations have previously been tested and recommended as drug carriers for peroral administration of poorly soluble porphyrin derivatives intended for photodynamical therapy. Based on those PLGA formulations the present study investigates conventional techniques like fluid bed granulation and tableting for conversion of such polymeric nanoparticle suspensions into solid dosage forms. Analytical methods like asymmetrical flow field-flow fractionation (AF4) and photon correlation spectroscopy (PCS) were used to assess changes of the nanoparticle properties during processing and the recovery after redispersion of the solid dosage forms. Preliminary experiments were conducted to demonstrate the feasibility of the granulation and tableting strategy. Afterwards, design of experiments (DoE) was used to determine formulation and process parameters with critical influence on several properties of the solid forms, in particular the recovery of nanoparticles during dissolution testing. Fluid bed granulation with aqueous PLGA nanoparticle suspensions and soluble carriers was shown to be a simple and high yield process for drying of the nanoparticles. The nanoparticle concentration of the granulation suspension and the ratio of the spraying rate and the atomization air pressure were critical for the physicochemical characteristics of the granules like density and particle size distribution (PSD) as well as for the re-dispersibility to nanoparticle suspensions of original properties. The granules were compressed to tablets without impairing the nanoparticle diameter and the recovery when an adequate level of filler and low compression forces were used.