Current Pharmaceutical Analysis - Volume 6, Issue 4, 2010

The application of classical methods for pellet coating thickness determination (weight gain, microscopic analysis, dissolution testing) is time-consuming or does not consider pellets loss during the coating procedure. Therefore, these methods are not optimal for process control during pellets coating. The aim of this study was to develop rapid and valid methods for the determination of pellets average coating thickness by near infrared spectroscopy (NIRS). NIRS is not the primary method; therefore reference data are required for calibration. Data obtained from two reference methods for coating thickness determination (microscopic analysis, a geometric model calculated from pellets weight and density) were mutually compared. A geometric model was chosen as the simpler, quicker and more robust reference method. The polymer films studied were ethylcellulose (EC) and Eudragit® RS (ERS) applied on pellets in a Wurster column. The calibration models were carried out by partial least squares (PLS) regression, with two factors for EC and ERS films, respectively. The PLS validation sets had r > 0.97, and a standard error of validation, 3.29 μm (range tested 10 - 70 μm), for the EC film and 1.10 μm (range tested 2 - 20 μm) for the ERS film. The obtained results clearly demonstrate the feasibility of NIRS as a part of quality control procedure in the pharmaceutical industry.

The power of NMR in elucidating the structure of isolated natural or synthetic compounds is well established. In recent years, NMR has also become an important tool for the qualitative and quantitative analysis of complex mixtures such as herbal medicines. The combination of 1H NMR and multivariate analysis, quite often used in metabolomics, leads to a metabolite fingerprint that can be used for quality control and identification of the origin (e.g. geographical or supplier). Compared with other methods and despite its relatively low intrinsic sensitivity, NMR has the advantages of simple sample preparation, high robustness, and non-selectivity thus providing global information in a single analysis but also specific structural characterization. Several examples of the application of 1H NMR in the quality control of herbal materials will be reviewed for highlighting the usefulness, advantages and limitations of NMR. The article will conclude on the Diffusion Ordered Spectroscopy 1H NMR method that can be regarded as a “virtual chromatography” for screening adulterations of herbal medicines.

Fluoroquinolones antibiotics are more effective pathogens resistant to other antibacterial, thus being regularly prescribed drugs in human and veterinary medicine. Many fluoroquinolones posses one or two stereogenic centers giving rise to enantiomers whose pharmacological properties and toxicity are often different. At the successive stages of drug discovery, the enantiomers of any chiral molecule must be isolated and analyzed and their enantiomeric purity determined. The present review summarizes recent developments on chiral separation of fluoroquinolones using chromatographic and electrophoretic techniques.

Turmeric (Curcuma longa L., Zingiberaceae family) is a well known Chinese herbal medicine. It possesses diverse pharmacologic effects including antioxidant, anti-inflammatory, antiproliferative and antiangiogenic activities. The main bioactive constituents of C. longa include sesquiterpenes, which are responsible for its aroma, and curcuminoids, which contribute to its bright yellow color. Both sesquiterpenes and curcuminoids exhibit great potential as therapeutic agents for various diseases including colon cancer, pancreatic cancer, diabetes and Alzheimer's disease. Particularly, curcumin, one of the major curcuminoids of turmeric, has been proved to be effective in cancer treatment and prevention by recent phase I clinical trials. In order to ensure the efficacy and safety of turmeric in clinical applications, sensitive and accurate analytical methods are of significance for the comprehensive quality control of C. longa. This review summarizes recent progress in the chemical analysis of sesquiterpenes and curcuminoids in turmeric.

During the 10-year period from 1999 to 2009, a rapid evolution was witnessed in the research of phytomedicines analysis. Radical developments in various chromatography methods have also taken place. Especially Ultra Performance LC spurred a revolution in liquid chromatography and brought regular analysis of new levels of efficiency. Another important addition has been the development of hyphenated techniques involving LC/MSn, LC/NMR, CE/MS, HSCCC/MS and TLC/MS, etc, which provide a more efficient analysis approach for complex systems in herbs, functional foods, and their related products. These achievements significantly enhance the possibility to find new lead compounds or traces of in vivo and in vitro metabolites of meaningful constituents, and provide both higher sample analysis throughput and better assay sensitivity for researchers.

Currently, in vivo-in vitro correlation (IVIVC) has become an effective tool to predict absorption behaviour of various pharmaceutical dosage forms. IVIVC in conjunction along with biopharmaceutical classification system (BCS) is considered to be a more effective alternative tool in view of the classical bioavailability studies. The most popular and recognized type of IVIVC are studies related to prolonged release oral dosage forms. The methodology for these tests is widely defined by FDA guidelines. Examples of IVIVC's for other pharmaceutical dosage forms like immediate release oral or parenteral prolonged release preparations are still limited. Especially, in the case of immediate release oral forms it seems to be such because of the lack of criteria, defined methodology, technical difficulties as well as troubles to find immediate release formulations comprising different extent of absorption. First, the examples of IVIVC for variable immediate release oral dosage forms were discussed along with the appropriate biopharmaceutical class and pharmacokinetic profile of an individual active substance. Proposed approaches were also analyzed in view of the estimation of their reliability. Moreover, some technical aspects of the building of IVIVC were discussed with the emphasis on the tools, which were applied to establish a correlation (e.g., time scaling factor, kind of pharmacokinetic analysis, medium, type of apparatus, dissolution procedure). Finally, the perspectives of IVIVC application for immediate release dosage forms as an alternative strategy to the bioavailability studies were estimated and then a proposal for the reliability criteria of IVIVC in the case of immediate release oral dosage forms was done.

Profiling of impurities in pharmaceutical products is an important part of the pharmaceutical manufacturing process and it is a regulatory expectation. Impurities may influence the safety and efficacy of the pharmaceutical products. Estimation of the impurity of pharmaceuticals provides excellent means for drug authorities to control the manufacturing process. To meet the challenges and to build high degree of purity in drug substances and drug products, it is required to carry out all the investigations for standards of drugs and impurities to get significant results. Different methods are available for impurity profiling; the most common analytical methods are based upon spectroscopic and chromatography separation techniques. One of the powerful tools of impurity profile is liquid chromatography (LC) coupled with mass spectroscopy (MS), and it is employed for the identification of impurities, natural products, drug metabolites, and proteins. LC-MS offers selectivity and specificity in both the chromatographic separation and detection steps, and is found as necessary steps to measure compounds at extremely low concentrations. LC-MS is steadily applied to scrutinize impurity during pharmaceutical product development and manufacturing process to support the safety evaluation of batches used in clinical studies. In this review, strategies for impurity profiling of pharmaceuticals with the applications of LC-MS, LCMS/ MS, LC-ESI/MS and LC-TOF/MS methods will be critically reviewed and discussed.