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

Autor: Viviane Lucia Beraldo-Araújo, Ana Flávia Siqueira Vicente, Marcelo van Vliet Lima, Anita Umerska, Eliana B. Souto, Lidia Tajber, Laura Oliveira-Nascimento
Přispěvatelé: Universidade do Minho
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Pharmaceutics. 626:122193
ISSN: 0378-5173
Popis: Available online 13 September 2022
The first step of a successful nanoformulation development is preformulation studies, in which the best excipients, 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 efficiency (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 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 spectrophotometric 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.
This study was part-financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001, CAPES-PrInt, Santander – Program of International Mobility number 31/2018 and Sao Paulo Research Foundation (FAPESP) grant numbers 2018/03666-3, 2019/09719-4 and 2020/08059-8. LT and AU acknowledge funding from Science Foundation Ireland, grants 15/CDA/3602 and 12/RC/2275_P2.
info:eu-repo/semantics/publishedVersion
Databáze: OpenAIRE
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