Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics br

Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs).During spray drying, very fast solvent evaporation is enabled by thegeneration of small droplets and exposure of these droplets to aheated drying gas. This fast solvent evaporation leads to anincreased viscosity that enables kinetic trapping of an activepharmaceutical ingredient (API) in a polymer matrix, which isfavorable for the formulation of supersaturated, kineticallystabilized ASDs. In this work, the relation between the solventevaporation rate and the kinetic stabilization of highly drug-loadedASDs was investigated. Accordingly, thermal gravimetric analysis(TGA) was employed to study the evaporation kinetics of sevenorganic solvents and the influence of solutes, i.e., poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), fenofibrate (FNB), and naproxen(NAP), on the evaporation behavior. At 10 degrees C below the boiling point of the respective solvent, methanol (MeOH) had the lowestevaporation rate and dichloromethane (DCM) had the highest. PVPVA decreased the evaporation rate for all solvents, yet this effectwas more pronounced for the relatively faster evaporating solvents. The APIs had opposite effects on the evaporation process: FNBincreased the evaporation rate, while NAP decreased it. The latter might indicate the presence of interactions between NAP and thesolvent or NAP and PVPVA, which was further investigated using Fourier transform-InfraRed (FT-IR) spectroscopy. Based onthesefindings, spray drying process parameters were adapted to alter the evaporation rate. Increasing the evaporation rate of MeOHand DCM enabled the kinetic stabilization of higher drug loadings of FNB, while the opposite trend was observed for ASDs of NAP.Even when higher drug loadings could be kinetically stabilized by adapting the process parameters, the improvement was limited,demonstrating that the phase behavior of these ASDs of FNB and NAP immediately after preparation was predominantlydetermined by the API-polymer-solvent combination rather than the process parameters applied

Jaar van publicatie:2022

Trefwoorden:amorphous solid dispersions, spray drying, solvent, evaporation, interactions, fenofibrate, naproxen

Toegankelijkheid:Open