Formulation, optimization, in vitro and in vivo evaluation of Nateglinide-loaded nanostructured lipid carriers for enhanced bioavailability.

Abstract

Purpose Nateglinide belongs to the meglitinide class, oral hypoglycemic drug used in the treatment of insulin-resistant (Type II) diabetes mellitus. Potential constraints associated with NTG delivery include poor aqueous solubility, short action time, and quick elimination, which causes variable bioavailability. Therefore, the aim of the present study was to develop and optimize NLCs formulations to improve the oral bioavailability and efficient delivery of NTG. Method NLCs were prepared by a modified HPH method using a box Behenken design approach. Glyceryl Monostearate and Miglyol 812, Acrysol EL 135 were chosen as solid lipid, liquid lipids, and surfactant respectively. Obtained NLCs were characterized for physicochemical properties, in-vitro drug release studies and pharmacokinetic parameters. Result NTG-NLCs exhibited small particle size ranging from 142.8 ± 1.67 to 252.7 ± 2.17 nm zeta potential in the ranging from 13.53 mV to 30.93 mV, Polydispersibility index of 0.343±0.071 to 0.417 ±0.058. The average encapsulation efficiency for the NLCs was 89.99%. Optimized NTG-NLC showed particle size 142.8 nm, zeta Potential, 30.93 mV, drug loading 16.04%, and entrapment efficiency 93.48 %. In a pharmacokinetic study, the relative oral bioavailability of nateglinide-NLC was increased by 3.77 times than that of pure nateglinide and 1.54 times than Glinate 60 marketed nateglinide formulation. The half-life of the drug was prolonged by 1.6 times. The solubility and bioavailability of nateglinide is enhanced, coupled with its prolonged release. Conclusion: NTG-NLC prepared by the modified HPH method is a promising technique to enhance in vitro drug release, bioavailability, and pharmacokinetics.