Profiles of drug substances, excipients, and related methodology最新文献

Sucrose octaacetate (SOA) is a United States National Formulary (NF) monograph compendial material (U.S. Pharmacopeia, 2008), and, as shown in Fig. 1, has eight acetate groups attached to a sucrose moiety. It is a natural product that has been extracted from the seeds of Annona cornifolia (Lima et al., 2011). It is nontoxic (Sigma-Aldrich, 2016) and has a number of uses based on its bitter taste. For example, sugar is rendered too bitter is eat at a concentration of 0.06% (w/w) SOA (Mann et al., 1992). SOA can form 255 different possible isomers and degradation products, all of which have a very low molar absorptivity. Its ultraviolet molar absorptivity at 210nm has been reported to be 439 absorption units/cm/M in water and 442 absorption units/cm/M in 30:70 acetonitrile-water.

Topiramate, 2,3:4,5-di-O-isopropylidene-β-d-fructopyranose sulfamate, is a potent antiepileptic drug with a broad spectrum of activity. It is effective in both partial and generalized seizures. Topiramate was also found to have significant efficacy in migraine prevention with considerable reductions in the frequency of migraine headaches. The most common adverse events, which may accompany the use of topiramate, are paresthesia, fatigue, decreased appetite, nausea, diarrhea, weight decrease and taste perversion. The weight loss observed with the use of topiramate in obese, epileptic patients, afforded the approval of this drug as an anti-obesity medication. This action is thought to be based on the selective inhibition of mitochondrial carbonic anhydrase isoforms. This profile is prepared to discuss and explain physical characteristics, proprietary and nonproprietary names of topiramate. It also includes methods of preparation, thermal and spectral behavior and methods of analysis. Pharmacokinetics, metabolism, excretion and pharmacology together with its uses and applications are also discussed.

A comprehensive profile of cefpodoxime proxetil including the nomenclatures, formulae, elemental composition, appearance, uses, and applications. The methods which were developed for the preparation of the drug substance and their respective schemes are outlined. The physical characteristics of the drug including the ionization constant, solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal behavior, and spectroscopic studies are included. The methods which were used for the analysis of the drug substance in bulk drug and/or in pharmaceutical formulations includes the compendial, spectrophotometric, electrochemical and the chromatographic methods. The other studies which was carried out on this drug substance are including the drug stability, pharmacokinetics, bioavailability, drug evaluation, comparison and several compiled reviews. Finally, more than two hundred references are listed at the end of this profile.

A comprehensive profile of levetiracetam is presented in this chapter which includes its description, formula, elemental analysis, appearance, uses and applications. Different earlier studies included for example methods of synthesis are described with its typical structural schemes. The profile also listed the drug's physical characteristics indicating its solubility, X-ray powder diffraction pattern, thermal methods of analysis as well as its spectroscopic characteristics. Different methods of analysis which includes compendial method of analysis, as well as reported method of analysis which include spectrophotometry, spectrofluorometry, electrochemical method, chromatographic method, and immunoassay method of analysis. The study was include drug stability, clinical pharmacology, e.g., mechanism of action, pharmacokinetic study. Around 70 references are recorded as a proof of this chapter.

Pharmaceutical preparations may contain a single ingredient or multi-ingredients as well as excipients. In multicomponent systems, specific analytical methods are required to determine the concentrations of individual components in the presence of interfering substances. Ultraviolet and visible spectrometric methods have widely been developed for the analysis of drugs in mixtures and pharmaceutical preparations. These methods are based on ultraviolet and visible multicomponent analysis and chemometrics (multivariate data analysis). The commonly used chemometric methods include principal component analysis (PCA); regression involving classical least squares (CLS), partial least squares (PLS), inverse least squares (ILS), principal component regression (PCR), multiple linear regression (MLR), artificial neural networks (ANNs); soft independent modeling of class anthology (SIMCA), PLS-discriminant analysis (DA); and functional data analysis (FDA). In this chapter, the applications of multicomponent ultraviolet and visible, derivative, infrared and mass spectrometric and spectrofluorimetric methods to the analysis of multi-ingredient pharmaceutical preparations, biological samples and the kinetics of drug degradation have been reviewed. Chemometric methods provide an efficient solution to calibration problems in the analysis of spectral data for the simultaneous determination of drugs in multicomponent systems. These methods facilitate the assessment of product quality and enhance the efficiency of quality control systems.

It is now well established that infrared absorption spectroscopy is a powerful technique for the physical characterization of pharmaceutical solids. Besides being a preferred methodology for identification purposes, one can use trends in the energy values in the spectra as a means to study the solid-state properties of the system. FTIR spectra are often used to evaluate the type of polymorphism existing in a drug substance, can be very useful in studies of the water contained within a hydrate species, and are emerging as a technique of choice for the study of cocrystal systems. In this review, an overview of the theoretical foundations for infrared spectroscopy will be presented, which will be supported by illustrations as to how the methodology can be used.

It is well known that the quality control (QC) of drugs derived from herbs (DDHs) has two main problems: first, DDHs are chemically complex mixtures, and second, the chemical contents of raw plant materials are affected by the site of cultivation, age of plants, methods of harvesting, and processing. QC is used by manufacturers to ensure the consistency, safety, and efficacy of the DDHs. QC of DDHs can be performed by two approaches, namely, marker-oriented and chemical pattern-oriented (metabolite profiling) using chromatographic methods. For having reliable results of any chemical analysis that will be performed in the QC laboratory, the method of analysis must be validated first before it can be routinely applied. Parameters of the validation method that should be evaluated for marker-oriented approach are stability, selectivity, linearity, trueness, precision, and robustness/ruggedness, while for metabolite profiling approach stability, intra- and interday precisions should be determined. Determination of instrumental and sample detection limit (DL), quantification limit (QL), and cutoff value is described in this review. Some relatively new validation methods that could correlate trueness and precision will be also discussed. The importance and application of metabolite profiling for a QC laboratory at pharmaceutical industry are discussed.