Development of in situ ion selective sensors for dissolution.

The dissolution of formulations of the drugs dapoxetine, paliperidone, cinnarizine, tetrazepam, mebeverine, loperamide, galantamine and ibuprofen was studied by an in-line potentiometric measurement system. The transpose of a Nikolskii-Eisenman type function performed the conversion of potential to percentage of dissolution. A novel gradient membrane electrode was developed especially for dissolution, varying continuously in composition from an ionically conducting rubber phase to an electronically conducting solid state PVC/graphite composite. The gradient part had a thickness of 200 microm. The electrodes life span exceeded 6 months. An ion exchange procedure was used to prepare them for one specific drug. This enabled us to use one universal electrode built to measure a wide array of drugs. The system parameters such as accuracy, reproducibility and linearity were presented with the data obtained for the drug dapoxetine. In dissolution, accurate measurements were possible from 10(-9) to 10(-3) M concentrations, for high log P drugs. The effect of t(90) response times on the measurement error was estimated. The t(90) response times of the electrodes were concentration dependent, and varied between 50 and 10 s for, respectively, 10(-6) and 10(-3) M concentrations. Potential drift was studied in detail. The measurements performed with these electrodes showed an accuracy of 1%, and inter- and intra electrode variabilities of 0.6 and 1.7%, respectively. The electrodes were successfully applied in colloidal media containing suspended matter, typically formed during dissolution of tablets. The advantages and pitfalls of potentiometry over the presently used techniques for dissolution testing are discussed.

Capillary electrophoresis as an orthogonal technique in HPLC method validation.

High-performance liquid chromatography is usually used to assay the main compound and organic impurity content of drug substance and drug product during pharmaceutical development. A crucial validation parameter of these methods is specificity--the ability to unequivocally assess the analyte in the presence of component expected to be present. Typically, these include impurities, degradation products, and matrices. Besides adequate chromatographic separation with sufficient selectivity, additional 2- or 3-D spectroscopic or chromatographic tools are frequently necessary for this purpose. In our current practice, HPLC is used with ultraviolet photodiode array detection and on-line mass spectrometry (LC-UVDAD-MS) during the assessment of specificity. Although this approach is very powerful and can solve the majority of problems, separation of isomers of the main compound is still difficult. Since HPLC usually cannot offer the required selectivity and because of the similar molecular weights, structural isomers are not specifically detected using LC-MS. Capillary electrophoresis, on the other hand, offers high separation efficiency and can be applied as an adjunct to HPLC. Therefore, a set of highly selective CE methods is used orthogonally in the specificity assessment of HPLC methods.