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

Cefdinir is a third-generation oral cephalosporin antibiotic. Nomenclature, formulae, elemental analysis, and appearance of the drug are mentioned. The uses and applications and the several methods described for its preparation of the drug are outlined. The profile contains the physical characteristics including: pKa value, solubility, X-ray powder diffraction, melting point, and differential scanning calorimetry. The ultraviolet spectrum, vibrational spectrum, nuclear magnetic resonance ((1)H and (13)C NMR) spectra and the mass spectrum and fragmentation patterns of cefdinir together with the corresponding figures and/or tables are all produced. This profile includes the monographs of the Japanese pharmacopeia and the United States pharmacopeia. The several reported analytical methods that had been reported of the analysis of cefdinir include: spectrophotometric, polarographic, voltammetric, and chromatographic methods. The pharmacokinetics and stability of the drug are also provided. About 80 references are listed at end of this comprehensive profile.

Vardenafil (VAR) is synthetic, highly selective, and potent inhibitor of phosphodiesterase-5 which competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. It is clinically approved for treatment of erectile dysfunction in men, including diabetic and postprostatectomy patients. Several methods of VAR synthesis are included in this review. UV spectroscopy of VAR showed a λmax of approximately 270nm, and IR spectroscopy principal peaks were observed at 3420 (NH), 1724 (CO), 1600 (CC, and CN), 1491 (CHCH) cm(-1). Characteristic carbonyl (CO) carbon was observed in nuclear magnetic resonance spectroscopy at 162.44ppm. The molecular mass was observed at m/z=488.9 (molecular weight=488.2) and the fragmentation pattern was studied using ion trap mass spectrometry. In addition, different analytical methods for determination of vardenafil are also described in this profile. Pharmacokinetic properties of VAR have great impact on efficacy. VAR is rapidly absorbed and slowly metabolized, with an absolute bioavailability of 15%. It is extensively metabolized by CYP3A4 into several metabolites, the most pharmacologically active of which is N-desethyl VAR (M1). The elimination half-life of VAR and M1 is about 4-5h. VAR is primarily excreted as metabolites in the feces and to a small extent in urine. VAR is generally well tolerated, with a favorable safety profile and few transient side effects, including headache, flushing, dyspepsia, and rhinitis.

This chapter includes the aspects of Menadione (vitamin K). The drug is synthesized by the use of itaconic acid obtained through Friedel-Craft condensation or by direct oxidation of the 2-methyl-1,4-naphthquinone. Vitamin K generally maintains healthy blood clotting and prevents excessive bleeding and hemorrhage, it is also important for maintaining healthy bone structure and for carbohydrate storage in the body. In addition, it is given to newborn babies born in hospitals to prevent the development of life-threatening bleeding caused by low prothrombin levels. The chapter discusses the drug metabolism and pharmacokinetics and presents various method of analysis of this drug such as compendial tests, electrochemical analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety.

Carvedilol ((2RS)-1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol), a β1-, β2-, and α1-adrenoreceptor blocker drug with antioxidant and antiproliferative effects, is indicated for treatment of hypertension, stable angina pectoris, and congestive heart failure. A profile of this drug substance is provided in this chapter and includes physical characteristics of Carvedilol (e.g., UV-vis, IR, NMR, and mass spectra). Details regarding the stability of Carvedilol in the solid state and solution phase are presented and methods of analysis (compendial and literature) are summarized. Furthermore, an account of the pharmacokinetics (ADME) and synthesis of Carvedilol are presented.

This chapter includes the aspects of melatonin. The drug is synthesized in the pineal gland starting from tryptophane or synthetically by using indole as starting material. Melatonin has been used as an adjunct to interleukin-2 therapy for malignant neoplasms, as contraceptive, in the management of various forms of insomnia, to alleviate jet lag following long flights, and finally as free radical scavenger and hence as an antioxidant and an anti-inflammatory. The chapter discusses the drug metabolism and pharmacokinetics and presents various method of analysis of this drug such as biological analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety.

A comprehensive profile on Butyl methoxy dibenzoylmethane, one of the most commonly used ultraviolet (UV) filters in topical sunscreen products, is prepared. This UV filter, often referred to as Avobenzone, has its main absorbance in the UVA I region of the spectrum and is susceptible to photodegradation. The profile contains the following sections: general information, use and mechanism of action, method of preparation, physical characteristics, methods of analysis, stability, and toxicity. The physical characteristics section includes the melting range, differential scanning calorimetry, partition coefficient, ionization constant, solubility, and UV, infrared, nuclear magnetic resonance ((1)H NMR and (13)C NMR) and mass spectrometry and X-ray powder diffractometry. The method of analysis section in addition to compendial identification and purity and assay methods includes thin-layer gas and high-performance liquid chromatography. The photostability and photostabilization of Butyl methoxy dibenzoylmethane, in addition to its toxicity, are also documented.

Moxidectin or F28249α is a potent endectocide and semisynthetic methoxime derivative of naturally occurring nemadectin. It is well known for the novel mode of action against a broad range of nematode and anthropod animal parasites. In this work, physicochemical and pharmaceutical aspects of moxidectin are described including stability, semisynthesis, purification processes, formulation compositions, impurities, and degradation pathways. Additional experiments such as DSC, XRD, and CHN analysis were carried out to complete the profile of moxidectin. The importance of safety and quality of drug substances was highlighted by chronological developments involving moxidectin and its analogues. The information gathered from the literature was used to trace the origins of moxidectin-related substances presented in the European Pharmacopeia (EP) compendial monograph. During the review, it was noticed that majority of impurities presented in the EP does not have any potential to increase with time in drug substance or formulated products; therefore, they do not require monitoring during stability studies. This also showed the requirement for further characterization of the impurities observed during long-term storage and development of stability indicating methods distinguishing between process impurities and the true degradation products. Furthermore, the stability of moxidectin in formulations is also reviewed in conjunction with known degradation routes and innovative ways to formulate products that are stable and effective at intended shelf life.

Aripiprazole is an atypical antipsychotic drug which belongs to the benzisoxazole derivatives. Aripiprazole is available in many salts and polymorphs forms. X-ray diffraction, IR spectroscopy, and DSC could be used for differentiating the polymorphs of aripiprazole. Some instrumental methods of analysis such as UV spectrophotometer, HPTLC, HPLC, and CE can be applied for analyzing aripiprazole and its impurities. Chromatography methods that have an MS/MS detector is the method of choice for analyzing aripiprazole and its metabolites. Bioavailability studies of the polymorphs of aripiprazole and their pharmaceutical preparations are very important to optimize the formulations of the dosage forms.

A profile of the analgesic tramadol hydrochloride ((1RS,2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride) is provided in this chapter and includes a summary of the physical characteristics known for this drug substance (e.g., UV/vis, IR, NMR, and mass spectra). Details regarding the stability of tramadol hydrochloride in the solid state and solution-phase are presented and methods of analysis (compendial and literature) are summarized. Furthermore, an account of biological properties and a description of the chemical synthesis of tramadol hydrochloride are given.