Indomethacin-5-fluorouracil-methyl ester dry emulsion: a potential oral delivery system for 5-fluorouracil.

OBJECTIVE: To produce a combined effect of indomethacin (IDM) and 5-fluorouracil (5FU) for cancer therapy, the side effects of IDM on the gastrointestinal (GI) tract were reduced and the oral adsorption of 5FU was improved. Indomethacin-5-fluorouracil-methyl ester (IFM) dry emulsion was prepared and evaluated as a potential oral delivery system for 5FU. METHODS: IFM was synthesized by formation of an ester between IDM and 5FU intermediate and then characterized by structure, melting point, solubility, apparent partition coefficient, and incubation with GI tract contents and plasma. Gum acacia and sodium carboxymethyl cellulose (CMC-Na) were applied as the adsorbent and solid carrier to prepare IFM dry emulsion. IFM dry emulsion was then characterized by reconstitution in water and in situ intestinal perfusion experiment. RESULTS: Physicochemical properties of the new synthesized compound confirmed the formation of IFM. Incubation of IFM in the contents of the GI tract and plasma revealed that IFM was not relatively stable in GI contents during the time period of transit through the GI tract, whereas it was very unstable in plasma and released 5FU rapidly. The IFM dry emulsion could be easily reconstituted in water, and the mean particle size was 2.416 microm. The absorption rate constant (K) for IFM with concentration of 2, 5, and 10 microg/mL in the in situ perfusion experiment were 0.473, 0.423, and 0.433/h, respectively, demonstrating passive diffusion of IFM across the biological membranes. CONCLUSION: This study indicates that the IFM dry emulsion may represent a potentially useful oral delivery system for 5FU.

Liquid chromatography-mass spectrometry method for the determination of thiamphenicol in rabbit tears.

A simple and sensitive liquid chromatography-mass spectrometry (LC-MS) method was described for the determination of thiamphenicol in rabbit tears. Chromatographic separation of the analyte was achieved on a C18 column using a mobile phase of acetonitrile and 10 mmol/l ammonium acetate solution (60:40, v/v). Selected ion monitoring (SIM) in negative mode was used for analyte quantification at m/z 354.4 for thiamphenicol and at m/z 137.1 for salylic acid. The run time was less than 6 min. Linearity over the concentration range of 0.032-32.0 ng/ml for thiamphenicol was obtained and the lower limit of quantification was 0.032 ng/ml. For each level of QC samples, inter- and intra-day precisions (R.S.D.) were

Investigation of microemulsion system for transdermal delivery of meloxicam.

A new oil-in-water microemulsion containing 0.375% meloxicam was developed in order to improve the skin permeability of meloxicam. Among various surfactants and cosurfactants investigated in the microemulsion system, polyoxyethylene sorbitan trioleate (Tween 85) showed excellent solubility and ethanol expressed skin permeation enhancing effect for meloxicam. The microemulsion existence ranges were defined through the construction of the pseudo-ternary phase diagram. The effect of the content of isopropyl myristate (IPM) and the effect of the mass ratio of the surfactant/cosurfactant (Km) on skin permeation of meloxicam were evaluated with excised rat skins. The optimum formulation with the highest skin permeation rate (5.40 microg/cm2/h) consisted of 0.375% meloxicam, 5% IPM, 50% Tween 85/ethanol (1:1) and water.