Comparison of Three Processes for Parenteral Nanoemulsion Production: Ultrasounds, Microfluidizer, and Premix Membrane Emulsification

Océane Alliod (1) , Eyad Almouazen (1) , Georgio Nemer (1) , Hatem Fessi (1) , Catherine Charcosset (1)

1 LAGEPP - Laboratoire d'automatique, de génie des procédés et de génie pharmaceutique

Nanoemulsions are of great interest for pharmaceutical applications, including parenteral dosage forms. However, their production is still limited and requires more efficient and adaptive technologies. The more common systems are high-shear homogenization like microfludizers (MF) at industrial scale and ultrasounds at research scale, both based on high energy limiting their application for sensitive drugs. Recently, a process based on premix membrane emulsification (PME) was developed to produce nanoemulsions. These three processes have been compared for the production of a model parenteral nanoemulsion containing all-trans-retinoic acid, a thermolabile molecule which is used in the treatment of acute promyelocytic leukemia in a parenteral form. Droplet size and active integrity were studied because of their major interest for efficacy and safety assessment. Regarding droplet size, PME produced monodispersed droplets of 335 nm compared to the other processes which produced nanoemulsions of around 150 nm but with the presence of micron size droplets detected by laser diffraction and optical microscopy. No real difference between the three processes was observed on active degradation during emulsifcation. However, regarding stability, especially at 40 o C nanoemulsions obtained with the microfluidizer showed a greater molecule degradation and unstable nanoemulsion with a 4 times droplet size increase under stress conditions.

Mots clés: Parenteral Nanoemulsion; Premix membrane emulsification; atRA; Microfludizer; Ultrasounds

Domaines: Chimie; Génie chimique; Sciences de l'ingénieur [physics]; Génie des procédés; Sciences du Vivant [q-bio]; Sciences pharmaceutiques

Océane Alliod, Eyad Almouazen, Georgio Nemer, Hatem Fessi, Catherine Charcosset. Comparison of Three Processes for Parenteral Nanoemulsion Production: Ultrasounds, Microfluidizer, and Premix Membrane Emulsification. Journal of Pharmaceutical Sciences, 2019, 108 (8), pp.2708-2717. ⟨10.1016/j.xphs.2019.03.026⟩. ⟨hal-02362258⟩