Quantitative analysis of binary polymorphs mixtures of fusidic acid by diffuse reflectance FTIR spectroscopy, diffuse reflectance FT-NIR spectroscopy, Raman spectroscopy and multivariate calibration.

Vibrational spectroscopic techniques such as infrared, near-infrared and Raman spectroscopy have become popular in detecting and quantifying polymorphism of pharmaceutics since they are fast and non-destructive. This study assessed the ability of three vibrational spectroscopy combined with multivariate analysis to quantify a low-content undesired polymorph within a binary polymorphic mixture. Partial least squares (PLS) regression and support vector machine (SVM) regression were employed to build quantitative models. Fusidic acid, a steroidal antibiotic, was used as the model compound. It was found that PLS regression performed slightly better than SVM regression in all the three spectroscopic techniques. Root mean square errors of prediction (RMSEP) were ranging from 0.48% to 1.17% for diffuse reflectance FTIR spectroscopy and 1.60-1.93% for diffuse reflectance FT-NIR spectroscopy and 1.62-2.31% for Raman spectroscopy. The results indicate that diffuse reflectance FTIR spectroscopy offers significant advantages in providing accurate measurement of polymorphic content in the fusidic acid binary mixtures, while Raman spectroscopy is the least accurate technique for quantitative analysis of polymorphs.

Quantitative analysis of oleic acid and three types of polyethers according to the number of hydroxy end groups in Polysorbate 80 by hydrophilic interaction chromatography at critical conditions.

A quantitative characterization of Polysorbate 80 is crucial for its many applications. In this paper we report a quick RP-HPLC method for the quantitative determination of Polysorbate 80. The hydrolysis of Polysorbate 80 to release oleic acid and three types of polyethers was first carried out. A chromatographic method based on liquid chromatography at critical conditions (LCCC) was then developed for an endgroup-based separation of low-molecular-mass polyether. With this method the polyether, irrespective of its molecular-mass, is separated according to endgroups (functionality) due to interactions of the polar endgroups with the hydrophilic stationary phase. The different types of polyethers and oleic acid were identified using on-line electrospray ionization mass spectrometry and quantified by evaporative light scattering detection.

Polyoxyethylene 40 stearate modulates multidrug resistance and enhances antitumor activity of vinblastine sulfate.

Multidrug resistance (MDR) is one of the major obstacles limiting the efficacy of cancer chemotherapy. Identification of new and effective MDR reversal agents is needed. In this study, the effects of polyoxyethylene 40 stearate (PS40) on MDR were evaluated via the transport of the P-glycoprotein (P-gp) substrate vinblastine sulfate (VBL) through Caco-2 cell monolayers and rat intestine tissue. The effects of PS40 on the antitumor activity of VBL were examined through 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and multidrug-resistant tumor-bearing mice. Results of the transport experiments showed that PS40 reduced VBL efflux. The cytotoxicity of vinblastine to K562/ADR cells was significantly enhanced when the cells were cotreated with 100 or 150 microg/mL PS40. In vivo data revealed that average tumor volume and average tumor weight were significantly less in the VBL+PS40 group than in the VBL group. The inhibition rate for tumor growth was increased from 0.06 (VBL group) to 0.84 (VBL+PS40 group). These results suggest that PS40 may be a potentially useful adjuvant to enhance the therapeutic effects of P-gp substrates.