Microwave-derivatized enhanced-spectrofluorophotometric characterization of nateglinide-loaded solid dispersion adsorbate and greenness profile assessment of method.

Abstract

Nateglinide is an oral meglitinide that treats diabetes. Nateglinide was determined in several commercial formulations using chromatographic and spectrophotometric methods in published research. Quality-by-design approach was applied to develop the in-house nateglinide-loaded Solid Dispersion Adsorbate (SDA) for improving bioavailability and solubility. To determine nanogram-level nateglinide concentration for the in-house developed nateglinide-SDA pharmacokinetics required time-consuming and expensive hyphenated analytical techniques such as LC-MS or UPLC-MS. Hence, a sensitive spectrofluorophotometric method was developed to estimate nateglinide using NBD-Cl (7-chloro-4-nitrobenzoxadiazole) as the fluorophore. Microwave-aided chemical derivatization of nateglinide with NBD-Cl sped up sample analysis. Chemical reaction solvents were eco-friendly to safeguard aquatic life and environment. The chemical process was optimized by quality by design approach using screening design and response surface modelling. The fluorescence intensity of nateglinide was found to be linear over the concentration range of 20-250 ng/mL with a correlation coefficient of 0.9978. The limits of detection and quantification were found to be 10 and 20 ng/mL respectively. Precision and robustness investigations of the spectrofluorimetric method showed less than 2% relative standard deviations. Nateglinide-SDA drug-release study and pharmacokinetics were performed using the sensitive spectrofluorophotometric method. The in-house developed nateglinide-SDA released 95% of the drug in 30 min time duration. In-house-developed nateglinide-SDA has 1.5 times the oral bioavailability of commercial formulations due to in-vivo absorption. The published analytical methods were compared to the enhanced-spectrofluorophotometric method for user-friendliness, efficiency, cost-of-analysis, and environmental friendliness. The proposed sensitive-spectrofluorophotometric method was found to be robust, rapid, eco-friendly, cost-effective, and simple for the estimation of nateglinide.