A quality by design approach for optimization of Lecithin/Span® 80 based nanoemulsions loaded with hydrophobic drugs

• Published in: Journal of molecular liquids 2021-01, Vol.321, p.114743, Article 114743
• Main Authors: Real, Daniel A., Hoffmann, Stefan, Leonardi, Darío, Goycoolea, Francisco M., Salomon, Claudio J.
• Format: Article
• Language: English
• Subjects: Central composite; Lecithin; Nanoemulsions; Placket Burmann; Quality by design; Span 80
• ISSN: 0167-7322
• DOI: 10.1016/j.molliq.2020.114743

Lately, nanoemulsions loaded with hydrophobic drugs have been successfully developed to improve the treatment of several global diseases. On this subject, a detailed study of the crucial role of the excipients and the experimental conditions used for these nanosystems is still required. Thus, the aim of this work was the development of nanoemulsions of Benzidazole (Class I, log P = 0.91), Praziquantel (Class II, log P = 2.44), Pyrimethamine (Class II/IV, log P = 2.69), Niclosamide (Class II/IV, log P = 4.5), and Triclabendazole (Class II/IV, log P = 5.9) using Span® 80, soybean lecithin and Miglyol® 812 as excipients. A Placket-Burman design was selected to identify the main parameters that influence in the desirable characteristics of such formulations. Then, a full factorial design was built to analyze the effect of the factors identified in the screening phase. Plackett-Burman design indicated that Miglyol® 812 and lecithin were the two most influencing factors on the hydrodynamic diameter of the systems. In addition, the association efficiency was influenced by the log P of each drug while the response stability in PBS was modified by Span® 80 and log P. The results of the full factorial design revealed that concentration of Miglyol® 812 and log P values of each drug have a remarkable impact on the stability of the nanosystems. The optimal conditions for the preparation of nanoemulsions were verified by other independent experiment and the results were in agreement with the predicted optimum values. Thus, this methodology could serve as an attracttive platform to deliver other hydrophobics compounds in stable nanoemulsions. [Display omitted] •A quality by design approach was successfully applied for optimization of Lecithin/Span® 80 based nanoemulsions.•Miglyol® 812 and lecithin were the most influencing factors on the hydrodynamic diameter of the nanoemulsions.•Stable O/W nanoemulsions exhibited particle sizes lower than 160 nm and an association efficiency between 55 and 97%.•Concentration of Miglyol® 812 and log P values have a remarkable impact on the stability of the nanoemulsions.•This methodology could serve as platform to deliver other hydrophobics drugs in stable nanoemulsions.