Box-Behnken based furosemide-nanostructured lipid carriers (NLCs) delivery system for improving oral bioavailability.

OBJECTIVE

The fabrication of furosemide (FSM) with enhanced oral bioavailability and encapsulation was achieved using a nanostructured lipid carriers (NLCs) drug delivery system.

SIGNIFICANCE: The uniform drug distribution is a barrier due to its low dose. The lipid-based delivery system was selected based on its poor solubility and permeability, limiting its poor partitioning and solubility in water-based polymeric delivery systems. The lipophilicity of the FSM makes it favorable to partition with triglyceride-based Compritol 888 ATO and oleic acid with minimized drug expulsion, high drug payload, and sustained release over extended time frames.

METHODS

The Organic and aqueous phases of the microemulsion were stabilized using Tween 80, a hydrophilic surfactant. Box-Behnken design-based optimization was done using alteration in various formulation variables to obtain nano-formulation with the lowest particle size and polydispersity, maximal zeta potential and entrapment efficiency.

RESULTS

Design-Expert yielded several optimized formulations with the desirability function. Maximum desirability was obtained at a particle size of around 178 nm, a surface charge of -19.6 mV, and an EE of above 85%.The in vitro release profile depicted 86.5% of cumulative release after 24 h whereas, in vivo pharmacokinetic study revealed an increase in Cmax from 0.48 µg/mL (FSM-Suspension) to 0.77 µg/mL (FSM NLCs) to increase the bioavailability to approx. 241% in FSM NLCs. The half-life escalation demonstrated that the residence time of the nanoparticles prolonged at the physiologic pH.

CONCLUSIONS

FSM-NLCs exhibited sustained release over a prolonged period, improved residence time in the body, and their action was prolonged.