Bupivacaine (S75:R25) Loaded in Nanostructured Lipid Carriers: Factorial Design, HPLC Quantification Method and Physicochemical Stability Study

Author(s): Gustavo Henrique Rodrigues Da Silva, Ligia Nunes de Morais Ribeiro, Viviane Aparecida Guilherme, Simone Ramos de Castro, Marcia Cristina Breitkreitz, Eneida de Paula*

Journal Name: Current Drug Delivery

Volume 15 , Issue 3 , 2018

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Graphical Abstract:


Background: Bupivacaine is the most used local anesthetic in surgical procedures, producing prolonged anesthesia. The major limiting factor for the clinical use of bupivacaine comes from its systemic toxicity. Nanostructured lipid carriers (NLC) are vehicles for sustained drug delivery that are able to minimize the toxicity and to increase the action time of lipophilic drugs.

Methods: This work reports a 22 factorial design, which elucidates the role of the lipids mixture in the NLC, towards an optimized formulation. It also provides a new method for bupivacaine S75:R25 (BVCS75) quantification in NLC. Moreover, physicochemical stability studies on the prepared NLC formulations were carried out by monitoring particle size, polydispersity, Zeta potential and BVCS75 encapsulation efficiency for 90 days, at 25°C.

Results: The factorial design showed that the liquid lipid Capryol 90® has a negative effect over particle size and PDI values while cetyl palmitate presented a positive effect in size. The analytical method was accurate, reproducible, specific and linear over the concentration range of 0.16-54.00 µg.mL-1 BVCS75 with limits of quantification and detection of 0.10 and 0.03 µg.mL-1, respectively. The validated method was used to quantify the BVCS75 encapsulation (55.5 ±2.8 %). Encapsulation did not affect the nanoparticles morphology (confirmed by Transmission Electron Microscopy), but increased their Zeta potential (from -15.7 to -37.0 mV). The NLC physical stability was maintained (particles: size < 170 nm, polydispersity <0.16, and number = 8.85 ±0.11 x 1013 particles.mL-1) during storage.

Conclusion: These results support further investigations on the use of BVCS75-in-NLC formulation for surgical anesthesia, aiming the development of a potent and less toxic nanostructured lipid carrier formulation for BVCS75.

Keywords: Bupivacaine, nanostructured lipid carriers, factorial design, HPLC, drug delivery, NTA.

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Article Details

Year: 2018
Published on: 27 March, 2018
Page: [388 - 396]
Pages: 9
DOI: 10.2174/1567201814666170726101113
Price: $65

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