[Show abstract][Hide abstract] ABSTRACT: An innovative versatile strategy using Total Error has been proposed to decide about the method's validity that controls the risk of accepting an unsuitable assay together with the ability to predict the reliability of future results. This strategy is based on the simultaneous combination of systematic (bias) and random (imprecision) error of analytical methods. Using validation standards, both types of error are combined through the use of a prediction interval or β-expectation tolerance interval. Finally, an accuracy profile is built by connecting, on one hand all the upper tolerance limits, and on the other hand all the lower tolerance limits. This profile combined with pre-specified acceptance limits allows the evaluation of the validity of any quantitative analytical method and thus their fitness for their intended purpose.
In this work, the approach of accuracy profile was evaluated on several types of analytical methods encountered in the pharmaceutical industrial field and also covering different pharmaceutical matrices. The four studied examples depicted the flexibility and applicability of this approach for different matrices ranging from tablets to syrups, different techniques such as liquid chromatography, or UV spectrophotometry, and for different categories of assays commonly encountered in the pharmaceutical industry i.e. content assays, dissolution assays, and quantitative impurity assays. The accuracy profile approach assesses the fitness of purpose of these methods for their future routine application. It also allows the selection of the most suitable calibration curve, the adequate evaluation of a potential matrix effect and propose efficient solution and the correct definition of the limits of quantification of the studied analytical procedures. Copyright
Full-text · Article · Dec 2012 · Drug Testing and Analysis
[Show abstract][Hide abstract] ABSTRACT: In this paper, we report the results of quality control based in physicochemical characterization and impurities determination of three samples of fluconazole drug substances marketed in Morocco. These samples were supplied by different pharmaceuticals companies. The sample A, as the discovered product, was supplied by Pfizer, while samples B and C (generics), were manufactured by two different Indian industries. Solid-state characterization of the three samples was realized with different physicochemical methods as: X-ray powder diffraction, Fourier-transformation infrared spectroscopy, differential scanning calorimetry. High performance liquid chromatography was used to quantify the impurities in the different samples. The results from the physicochemical methods cited above, showed difference in polymorph structure of the three drug substances. Sample A consisted in pure polymorph III, sample B consisted in pure polymorph II, sample C consisted in a mixture of fluconazole Form III, form II and the monohydrate. This result was confirmed by differential scanning calorimetry. Also it was demonstrated that solvents used during the re-crystallization step were among the origins of these differences in the structure form. On the other hand, the result of the stability study under humidity and temperature showed that fluconazole polymorphic transformation could be owed to the no compliance with the conditions of storage. The HPLC analysis of these compounds showed the presence of specific impurities for each polymorphic form, and a possible relationship could be exist between impurities and crystalline form of fluconazole.
Full-text · Article · Dec 2012 · Journal of Pharmaceutical Analysis
[Show abstract][Hide abstract] ABSTRACT: The dosage of the impurities of fluconazole was realized on three different samples from active raw materials marketed in Morocco. Sample a was supplied by the pharmaceutical company that discovered the drug (Pfizer, Ireland) while samples b and c were manufactured by two different Indian companies. These samples belong to three different polymorphic forms: the first one corresponds to the pure polymorph III, the second to the pure polymorph II, while the third is constituted by a mixture of two polymorphs (II, III) and a monohydrate form. The HPLC/UV methods adopted for the dosage of the impurities of fluconazole are described, in an internal monograph, by an Indian manufacturer. The results showed that the percentages in impurities are less than the limits fixed by the European and US Pharmacopoeias. The comparative analysis of the results of dosage of the impurities showed the presence of specific impurities for every polymorphic form. However, a possible relation impurities-crystalline form of the fluconazole was determined. Solvents used in the process of synthesis and purification could be at the origin of these differences.
[Show abstract][Hide abstract] ABSTRACT: Since 2002, the characterization of crystalline polymorphism has become an integral stage of drug substance (DS) development and quality control. The results of a comparative physicochemical characterization study of three samples (A, B and C) of fluconazole DS commercially available in Morocco are reported herein. Sample A was supplied by the pharmaceutical company that discovered the drug (Pfizer) while samples B and C were manufactured by two different Indian companies. Fluconazole was shown to have different crystal structures in the three samples. Three polymorphs and a hydrated form were distinguished. The samples were characterized using various physicochemical methods: X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). XRD and FTIR enabled differentiation of the three DS: sample A consisted in pure polymorph III, sample B consisted in pure polymorph II, sample C consisted in a mixture of two polymorphs and a hydrated form (III, II and the monohydrate). The findings were confirmed by DSC.
No preview · Article · Jan 2007 · S.T.P. Pharma Pratiques