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 such as microfludizers 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 3 processes have been compared for the production of a model parenteral nanoemulsion containing all-trans retinoic acid, a thermolabile molecule that 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 with the other processes that 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 3 processes was observed on active degradation during emulsifcation. However regarding stability, especially at 40°C, nanoemulsions obtained with the microfluidizer showed a greater molecule degradation and unstable nanoemulsion with a 4-times droplet size increase under stress conditions.
Keywords: atRA; microfludizer; parenteral nanoemulsion; premix membrane emulsification; ultrasounds.
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