Prilling of fatty acid-API suspensions: processability and characterization

Current study evaluated the processability and characteristics of prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension instead of previously studied API/FA solutions to enlarge the application field of prilling. Metformin hydrochloride (MET) and paracetamol (PAR) were used as model APIs while both the effect of drug load (10% to 40%) and FA chain length (C14 to C22) were evaluated. Prevention of nozzle obstruction due to large or agglomerated API particles in the molten FA was achieved via API sieving while sedimentation during processing was avoid via equipment modifications. Finally, the API/FA suspensions were processable on lab-scale prilling equipment without thermal degradation, nozzle obstruction or sedimentation in function of processing time. The processability of API/FA suspensions was only limited by the viscosity of the molten mixture which was mainly affected by the size and shape of the API particles but independent of the FA chain length. A lower API particle size and aspect ratio, resulted in a higher amount of particle-particle interactions and consequently a higher viscosity at equal drug load. Current study also gained more insight in the solidification behavior of API/FA based formulations in liquid nitrogen via high speed camera analysis and rapid heat calorimetry. The collected prills were spherical (AR ≥ 0.89 8) with a smooth surface (sphericity ≥ 0.91 4) and a stable particle size of ± 2.3mm and 2.4mm for MET and PAR prills respectively, independent of the drug load and/or FA chain length. In vitro drug release evaluation revealed a faster drug release at higher drug load, higher API water solubility and shorter FA chain length. Except for a 10% MET in behenic acid (C22) formulation since the low viscosity of the mixture resulted in an inhomogeneous API distribution in the prill, while stearic acid (C18) based formulations had an increased drug release due to their high porosity. Solid state characterization via XRD and Raman spectroscopy proved the preservation of API and FA crystallinity after thermal processing via prilling and during storage. Evaluation of the similarity factor proved a stable drug release (f 2 >50) of both MET and PAR prills after storage at 25°C or 40°C for 6 months. Malvern Instruments, Malvern, UK) was applied on dispersions of the API in Miglyol 812® (IOI Oleo GmbH, which were vortexed and subsequently sonicated for 10 min. After transfer to the wet sample dispersion unit (1500 rpm) to obtain an obscuration of 10 - 30%, the samples were analysed using a 300RF lens (Malvern Instruments, Malvern, UK). d 50 and d 90 were determined on a volume based distribution after performing measurements in triplicate. of MET, the in vitro drug release rate out of MET prills was higher and less susceptible to pH differences and/or surfactants present in the dissolution in comparison with PAR prills. Solid state characterization via XRD and Raman spectroscopy proved the preservation of API and FA crystallinity after thermal processing via prilling and during storage. Drug release of both MET and PAR prills was stable during 6m storage at 25°C and 40°C.