19F Nuclear Magnetic Resonance Spectrometric Determination of the Partition Coefficients of Flutamide and Nilutamide (Antiprostate Cancer Drugs) in a Lipid Nano-Emulsion and Prediction of Its Encapsulation Efficiency for the Drugs

Abstract

Abstract. To design a useful lipid drug carrier having a high encapsulation efficiency (EE%) for the antiprostate cancer drugs flutamide (FT) and nilutamide (NT), a lipid nano-emulsion (LNE) was prepared with soybean oil (SO), phosphatidylcholine (PC), and sodium palmitate, and the partition coefficients (K p s) of the drugs for the LNE were determined by 19 F nuclear magnetic resonance (NMR) spectrometry. The 19 F NMR signal of the trifluoromethyl group of both drugs showed a downfield shift from an internal standard (trifluoroethanol) and broadening according to the increase in the lipid concentration due to their interaction with LNE particles. The difference in the chemical shift (Δδ) of each drug caused by the addition of LNE was measured under different amounts of LNE, and the K p values were calculated from the Δδ values. The results showed that FT has higher lipophilicity than NT. The total lipid concentration (SO + PC) required to encapsulate each drug into LNE with an EE% of more than 95% was calculated from the K p values as 93.3 and 189.9 mmol/L for FT and NT, respectively. For an LNE prepared with the total lipid concentration of 215 mmol/L, the predicted EE% values were 98 and 96% for FT and NT, respectively, while the experimental EE% values determined by a centrifugation method were approximately 99% for both drugs. Thus, the 19 F NMR spectrometric method is a useful technique to obtain the K p values of fluorinated drugs and thereby predict the theoretical lipid concentrations and prepare LNEs with high EE% values.

Application of Ultra-Centrifugation and Bench-Top 19F NMR for Measuring Drug Phase Partitioning for the Ophthalmic Oil-in-Water Emulsion Products

“…The absolute chemical shift values of nuclei F28 and F29 were slightly different among spectra of different samples, e.g., the largest 0.25 ppm difference was observed in peak F29 (Fig. 2a), which was attributed to the differences in excipient chemicals from sample to sample (12) and no reference correction to the field drifting. In this study, because F28 and F29 peaks were well-resolved with a consistent chemical shift separation of 21.63 ± 0.05 ppm, the small peak drifts (e.g., 0.25 ppm) do not affect the peak integration and quantification.…”

“…DFPN chemical shift assignments were taken from the literature (13). The absolute chemical shifts values were slightly different due to the differences in residual chemicals including oil (12) and the field drifting in the bench-top NMR spectrometer The DFPN water phase partition for all the 11 tested formulations Table I.…”

Porous Nanostructured Chromium-Doped Tungsten Oxide Electrocatalysts for Flutamide and Nilutamide Detection

“…Therefore, the determination of NLTM is biologically vital and of concern. In previous years, NLTM detection was carried out using analytical methods such as micellar electrokinetic chromatography, spectrophotometric/flow systems, 19 F-NMR spectroscopy, amperometry, and voltammetric techniques. − …”

“…42 Therefore, the determination of NLTM is biologically vital and of concern. In previous years, NLTM detection was carried out using analytical methods such as micellar electrokinetic chromatography, 43 spectrophotometric/flow systems, 44 19 F-NMR spectroscopy, 45 amperometry, 46 and voltammetric techniques. 47−51 The traditional methods mentioned above exhibit certain drawbacks, including significant time consumption, the need for skilled personnel, expensive instrumentation, and high complexity.…”