title: 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: 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 (Kps) of the drugs for the LNE were determined by19F nuclear magnetic resonance (NMR) spectrometry. The19F 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 Kpvalues 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 Kpvalues 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, the19F NMR spectrometric method is a useful technique to obtain the Kpvalues of fluorinated drugs and thereby predict the theoretical lipid concentrations and prepare LNEs with high EE% values.
authors: Department of Analytical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan. takegami@mb.kyoto-phu.ac.jp.
authors: Shigehiko
authors: S
authors: Takegami
authors: Department of Analytical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan.
authors: Keisuke
authors: K
authors: Kitamura
authors: Department of Analytical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan.
authors: Mayuko
authors: M
authors: Ohsugi
authors: Department of Analytical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan.
authors: Atsuko
authors: A
authors: Konishi
authors: Department of Analytical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, Kyoto, 607-8414, Japan.
authors: Tatsuya
authors: T
authors: Kitade
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry*; D005485:Flutamide / Q000737:chemistry*; D006801:Humans; D048289:Imidazolidines / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004655:Emulsions; D048289:Imidazolidines; D008055:Lipids; D010713:Phosphatidylcholines; C021277:nilutamide; D005485:Flutamide
keywords: 19F NMR spectrometry; antiprostate cancer drug; encapsulation efficiency; lipid nano-emulsion; partition coefficient