Optimization of the supercritical fluidized bed process for sirolimus coating and drug release

Directly coating an active pharmaceutical ingredient (API) onto excipient granules has been a common approach to prepare solid dosage forms. The combination of supercritical anti-solvent (SAS) and fluidized bed (FB) coating technology (SAS-FB) has the advantages of preventing nanoparticles aggregation, oxidation and light exposure. However individual operating parameters and factors which contribute to the overall coating efficiency remain to be defined. Sirolimus is an immunosuppressive agent for preventing the rejection of organ transplants and this drug is sensitive to light exposure and high temperature. Our study used sirolimus as the model API to evaluate parameters including temperature, pressure, drug concentration, mass, material and diameter of carrier, CO2 flow rate and solvent in the SAS-FB process. By optimizing these parameters, we achieved a 3.5-fold enhancement of the coating efficiency over the standard condition. A series of characterizations of the sirolimus coated particles were performed from which scanning electron microscopy and Raman mapping confirmed that the sirolimus particles were uniformly coated on carriers as cuboid particles; X-ray powder diffraction showed that processed sirolimus is crystalline but has lower crystallinity than the API, and fourier transform infrared spectroscopy and differential scanning calorimeter confirmed that there is no chemical interaction between sirolimus and carriers after SAS-FB processing. Finally compared to sirolimus alone, sirolimus coated particles displayed a faster dissolution and higher bioavailability. Collectively, our optimized operation parameters for SAS-FB coating technique provide a useful guidance for achieving higher efficiency of drug coating and faster release rate of sirolimus pellets, which has the potential to apply to other APIs.