An-Bang Wu

DEVELOPMENT OF A LIQUID CHROMATOGRAPHIC METHOD FOR BIOANALYTICAL APPLICATIONS WITH SILDENAFIL

An improved HPLC method was developed for the determination of sildenafil concentrations in plasma. Analysis of sildenafil in plasma samples was simplified by utilizing a one-step liquid-liquid extraction after alkaline treatment of only 1 ml of plasma. The lower limit of quantitation was 10 ng/ml with a coefficient of variation of less than 20%. A linear range was found to exist from 10 to 1000 ng/ml. This HPLC method was validated with precisions (coefficient of variation, C.V.) for inter- and intra-day runs of 0.41-11.15% and 0.36-8.05%, respectively, and accuracies (the relative error of the mean, REM) for inter- and intra-day runs of -8.72-6.81% and 0.41-11.15%, respectively. A bioavailability study of sildenafil was performed on one normal healthy male volunteer by analyzing sildenafil plasma concentrations with this validated HPLC method. Results demonstrated that this HPLC method is appropriate for applications to bioavailability studies of sildenafil. In addition, an example of the influence of the co-administration of grapefruit juice on sildenafil pharmacokinetics in a healthy volunteer is presented.

Effect of Tocopheryl Polyethylene Glycol Succinate on the Percutaneous Penetration of Minoxidil from Water/Ethanol/Polyethylene Glycol 400 Solutions

ABSTRACT We described to achieve the local retention of minoxidil which has penetrated the skin with minimization of its absorption into the general circulation and elimination of local irritation induced by propylene glycol. The effect of tocopheryl polyethylene glycol succinate (TPGS) on the penetration flux of minoxidil and its retention in the skin from topical minoxidil formulations consisting of water, alcohol, and polyethylene glycol 400 was characterized by an experimental design of ten solvent formulations in this study. Results show that the addition of TPGS was only able to improve the solubility of minoxidil in those solvent systems containing higher proportions of water and PEG 400, and the extent of improvement was also more profound with the addition of TPGS at concentrations higher than 5%. For those solvent systems containing a higher fraction of alcohol, an insignificant change in minoxidil solubility with increasing added amounts of TPGS was noted even with the tendency to decrease the solubility of minoxidil with higher amounts of TPGS. Increasing the amount of TPGS added gradually increased the flux and the corrected flux from solvent formulations with a lower solubility parameter, but decreased those from solvent systems with a higher solubility parameter. With the addition of TPGS, solvent formulation F6 (alcohol:PEG 400 of 50:50) was demonstrated to be the optimal choice by having an improved local effect and a reduced systemic effect compared to the reference of 2% Regaine®. Tocopheryl polyethylene glycol succinate (TPGS) was mainly retained locally in the stratum corneum, and the amount was proportional to the increase in the amount of TPGS added to these ten solvent formulations.

Effect of hydroxypropyl-β-cyclodextrin on the solubility, photostability and in-vitro permeability of alkannin/shikonin enantiomers

The influence of hydroxypropyl-β-cyclodextrin (HPCD) on the solubility, photostability, and the in-vitro permeability of alkannin/shikonin enantiomers (A/S) was investigated. Solubility of A/S increased approximately 200 fold at 50% HPCD. The phase-solubility diagram revealed the formation of a 1:1 inclusion complex of A/S-HPCD and a stability constant (ks) of 260.5 M−1. Addition of HPCD significantly decreased the photochemical decomposition rate of A/S at pH 9.0. The apparent-first-order photochemical decomposition rate constants of free and complexed A/S were calculated from the Lineweaver-Burk plot to be 0.329 and 0.156 h−1, respectively. The in-vitro permeability study showed that the release of A/S from four test bases followed a Higuchi release model. The presence of HPCD enhanced the A/S release rate by 34 and 54 fold in cream and gel form, respectively, at one-tenth A/S concentration of the control preparation-Shiunko ointment.

Photolysis of indomethacin in methanol

Abstract A novel photo-oxidation product containing a six-membered 1,2-dioxane ring was isolated from the photolysis of indomethacin in methanol and a possible mechanism is proposed.

Separation and structure determination of nicardipine photoproducts by LC-ESI-MS

A sample of 0.104 M nicardipine in methanol was photoirradiated with a Philips 400 W UV lamp for 3 h in a photochemical chamber. A total of four major photoproducts were found from the HPLC chromatogram. The same sample was used for taking LC-MS, while eight major photoproducts were observed and the structures elucidated by analyzing the CID patterns of their respective mass spectra. A reaction scheme of nicardipine is proposed that the photochemical reactions occur mainly via oxidation of 1,4-dihydropyridine moiety, following the stepwise photo-reduction of the m-nitro group and demethylation of the ester group at 5-position of the pyridine ring.