Levofloxacin in nanostructured lipid carriers: Preformulation and critical process parameters for a highly incorporated formulation

Author(s)

Beraldo-Araujo, Viviane Lucia ; Siqueira Vicente, Ana Flavia ; Lima, Marcelo van Vliet ; Umerska, Anita ; Souto, Eliana B. ; Tajber, Lidia ; Oliveira-Nascimento, Laura

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 626, p. 13-pg., 2022-10-15.

Abstract

The first step of a successful nanoformulation development is preformulation studies, in which the best excipi-ents, drug-excipient compatibility and interactions can be identified. During the formulation, the critical process parameters and their impact must be studied to establish the stable system with a high drug entrapment effi-ciency (EE). This work followed these steps to develop nanostructured lipid carriers (NLCs) to deliver the antibiotic levofloxacin (LV). The preformulation studies covered drug solubility in excipients and thorough characterization using thermal analysis, X-ray diffraction and spectroscopy. A design of experiment based on the process parameters identified nanoparticles with < 200 nm in size, polydispersity <= 0.3, zeta potential-21 to-24 mV, high EE formulations (>71 %) and an acceptable level of LV degradation products (0.37-1.13 %). To the best of our knowledge, this is the first time that a drug degradation is reported and studied in work on nanostructured lipids. LV impurities following the NLC production were detected, mainly levofloxacin N-oxide, a degradation product that has no antimicrobial activity and could interfere with LV quantification in spectro-photometric experiments. Also, the achievement of the highest EE in lipid nanoparticles than those described in the literature to date and the apparent protective action of NLC of entrapped-LV against degradation are important findings. (AU)

• FAPESP's process: 20/08059-8 - Multifunctional molecule delivery to treat pulmonary infections and consequent local inflammation
• Grantee: Laura de Oliveira Nascimento
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/09719-4 - Development and physical-chemical characterization of nanostructured antibiotics
• Grantee: Ana Flávia Siqueira Vicente
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/03666-3 - Use of nanostructured carriers to load combined antibiotics
• Grantee: Viviane Lucia Beraldo de Araújo
• Support Opportunities: Scholarships in Brazil - Doctorate