Solidification of cinnarizine self-nanoemulsifying drug delivery systems by fluid bed coating: optimization of the process and formulation variables.

Abstract

Self-nanoemulsifying drug delivery systems (SNEDDS) offer an efficient choice to improve the poor dissolution and erratic bioavailability of poorly-water soluble drugs. However, liquid SNEDDS experience some manufacturing and stability limitations. To overcome these limitations, the current study aims to investigate and optimize the solidification of cinnarizine (CN) liquid SNEDDS onto pellets by fluid bed coating. The study involved optimization of process and formulation variables. The coated self-nanoemulsifying pellets (SNEP) were characterized, their droplet size and dissolution profiles were compared to the corresponding liquid SNEDDS. Higher spray/microclimate air pressure led to minimal agglomeration and minimal spray drying. However, slight increase in inlet air volume above 35 m3/h led to extensive spray drying. The optimized coating formula included oleic acid/Imwitor308/Cremophor El (25/25/50) as liquid SNEDDS, HPMC E3 as coating polymer and Plasacryl™T20 as anti-tacking agent. The optimum concentration of coating solution was 15% and optimum SNEDDS proportion in the coating layer was 40%. The droplet size of reconstituted SNEP was significantly (p < 0.05) higher than liquid SNEDDS, yet the SNEP aqueous dispersion was still within the nano-metric scale. Pure CN showed sharp precipitation upon shifting the media from pH 1.2 to 6.8. In contrast, Both SNEP and liquid SNEDDS maintained >85% CN in solution, even at pH 6.8. Therefore, CN-SNEP seems to be an excellent dosage form that maintains the solubilization benefits of liquid SNEDDS, overcomes their limitations along with the additional benefits of solid dosage form.