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

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.

Ganciclovir is synthetic nucleoside analog of guanine closely related to acyclovir but has greater activity against cytomegalovirus. This comprehensive profile on ganciclovir starts with a description of the drug: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and application of the drug are explained. The methods that were used for the preparation of ganciclovir are described and their respective schemes are outlined. The methods which were used for the physical characterization of the dug are: ionization constant, solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The chapter contains the spectra of the drug: ultraviolet spectrum, vibrational spectrum, nuclear magnetic resonance spectra, and the mass spectrum. The compendial methods of analysis of ganciclovir include the United States Pharmacopeia methods. Other methods of analysis that were reported in the literature include: high-performance liquid chromatography alone or with mass spectrometry, electrophoresis, spectrophotometry, voltammetry, chemiluminescence, and radioimmunoassay. Biological investigation on the drug includes: pharmacokinetics, metabolism, bioavailability, and biological analysis. Reviews on the methods used for preparation or for analysis of the drug are provided. The stability of the drug in various media and storage conditions is reported. More than 240 references are listed at the end of the chapter.

Tolfenamic acid (TA) is a nonsteroidal antiinflammatory drug and belongs to the group of fenamates. It is used as a potent pain reliever in the treatment of acute migraine attacks, and disorders like dysmenorrhea, rheumatoid, and osteoarthritis. TA has shown excellent in vitro antibacterial activity against certain ATCC strains of bacteria when complexed with bismuth(III). It has also been reported to block pathological processes associated with Alzheimer's disease. In the recent past, TA has also been used as a novel anticancer agent for the treatment of various cancers. In view of the clinical importance of TA, a comprehensive review of the physical and pharmaceutical properties and details of the various analytical methods used for the assay of the drug in pharmaceutical and biological systems has been made. The methods reviewed include identification tests and titrimetric, spectrophotometric, chromatographic, electrochemical, thermal, microscopic, enzymatic, and solid-state techniques. Along with the analytical profile, the stability and degradation of TA, its pharmacology and pharmacokinetics, dosage forms and dose, adverse effects and toxicity, and interactions have been discussed.

Mirtazapine is one of antidepression which is used mainly in the treatment of depression, moreover, it is sometimes used in the treatment of anxiety disorders, insomnia, nausea, and vomiting, and to produce weight gain when desirable. The action of mirtazapine is an antagonist of certain adrenergic and serotonin receptors, and, furthermore, the drug is used strong as antihistamine, and it is occasionally defined as a noradrenergic and specific serotonergic antidepressant (NaSSA). The comprehensive profile of mirtazapine gives more detailed information about nomenclature, formulae, elemental analysis, and appearance. In addition, the numerous methods of drug synthesis are summarized. Also the profile covers the physicochemical properties as: the value of pK_a, drug solubility, melting point, X-ray powder diffraction, and analysis methods for example: (compendial, electrochemical, spectroscopic, and method of chromatographic). Besides that, the profile covered pharmacological profile and clinical pharmacokinetics in subtitle's (absorption, distribution, metabolism, and elimination). About 100 references were given as a proof of the above-mentioned studies.

Cinacalcet hydrochloride is a calcimimetic agent that increases the sensitivity to the extracellular calcium of the calcium-sensing receptors of the parathyroid gland which regulates parathyroid hormone secretion. This comprehensive profile on cinacalcet hydrochloride starts with a description: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and applications of the drug are included. The methods of preparation of cinacalcet hydrochloride are described and their respective schemes are outlined. The physical characterization of the drug is: ionization constant, solubility, X-ray powder diffraction (XRPD) pattern, crystal polymorphs, melting point, and differential scanning calorimetry. The spectral characteristics of the drug include: ultraviolet spectrum, vibrational spectrum, ¹H and ¹³C nuclear magnetic resonance spectra, and the mass spectrum. The methods of analysis of the drug include: spectrophotometry, electrophoresis, fluorimetry, and high-performance liquid chromatography alone or with mass spectrometry. The stability of the drug in various media and storage conditions are reported. Biological studies on the drug include: the metabolism pharmacokinetics and pharmacodynamics. More than 100 references are listed at the end of the chapter.

Tolterodine tartrate belongs to the family of muscarinic receptor antagonists and is indicated for the treatment of overactive urinary bladder syndrome. This chapter provides an overview of physical, analytical, and ADME profiles; highlights methods of chemical synthesis; and discusses stability of tolterodine as a free base and/or its l-tartrate salt in solution and in the solid state. The information presented in this chapter is based on the peer-reviewed literature, compendial reports (USP, EP), and authors' data. Patent literature is included only in a few instances.

Olmesartan is an angiotensin receptor blockers with actions similar to those of losartan; it is used for the treatment of high blood pressure by relaxing blood vessels for this reason blood can flow more easily. It could be used alone or in combination with other antihypertensive drugs. This chapter gives a comprehensive profile of olmesartan, containing detailed nomenclature, formulae, elemental analysis, and appearance of the drug. In addition this chapter also describes several methods of synthesis and usage of the olmesartan. The profile covers the physicochemical properties including pK_a value, solubility, X-ray powder diffraction, melting point, and procedures of analysis (compendial, spectroscopic, electrochemical, and chromatographic techniques of analysis). Comprehensive pharmacology is also presented (pharmacological actions, therapeutic uses and dosing, interactions, and adverse effects and precautions). Eighty references were given as a proof of the above-mentioned studies.