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

Salmeterol xinafoate is a potent and a long-acting β2-adrenoceptor agonist. It is prescribed for the treatment of severe persistent asthma and chronic obstructive pulmonary disease. Different methods were used to prepare (R)-(-)-salmeterol such as: mixing a sample of 4-benzyloxy-3-hydroxymethyl-ω-bromoacetophenone with sodium lauryl sulfate and the mixture was added to the microbial culture of Rhodotorula rubra, treatment of p-hydroxyacetophenone with Eschenmoser's salt and carbonate exchange resin followed by a sequence of supported reagents and scavenging agents or via Rh-catalyzed asymmetric transfer hydrogenation. The enantioselective synthesis of (S)-salmeterol was achieved via asymmetric reduction of the azidoketone 4 by Pichia angusta yeast. Physical characteristics of salmeterol xinafoate were confirmed via: X-ray powder diffraction pattern, thermal analysis and UV, vibrational, nuclear magnetic resonance, and mass spectroscopical data. Initial improvement in asthma control may occur within 30 min following oral inhalation of salmeterol in fixed combination with fluticasone propionate. Clinically important improvements are maintained for up to 12 h in most patients. It is extensively metabolized in the liver by hydroxylation, thus increased plasma concentrations may occur in patients with hepatic impairment.

A comprehensive profile of prasugrel HCl is reported herein with 158 references. A full description including nomenclature, formulae, elemental analysis, and appearance is included. Methods of preparation for prasugrel HCl, its intermediates, and derivatives are fully discussed. In addition, the physical properties, analytical methods, stability, uses and applications, and pharmacology of prasugrel HCl are also discussed.

Telmisartan is an angiotensin-II receptor antagonist (ARB) used in the treatment of hypertension. Generally, angiotensin-II receptor blockers such as telmisartan bind to the angiotensin-II type 1 receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. The present study gives a comprehensive profile of telmisartan, including detailed 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 physicochemical properties including: pKa value, solubility, X-ray powder diffraction, melting point, and methods of analysis (including compendial, electrochemical, spectroscopic, and chromatographic methods of analysis). Developed validated stability-indicating (HPLC and biodiffusion assay methods under accelerated acidic, alkaline, and oxidative conditions, in addition to effect of different types of light, temperature, and pH. Detailed Pharmacology also presented (Pharmacological actions, Therapeutic uses and Dosing, Interactions, and adverse effects and precautions). More than 80 references were given as a proof of the above-mentioned studies.

Glutathione is an endogenous peptide with antioxidant and other metabolic functions. The nomenclature, formulae, elemental composition, and appearance and uses of the drug are included. The methods used for the synthesis and biosynthesis of glutathione are described. This profile contains the physical characteristics of the drug including: solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The spectral methods that were used for both the identification and analysis of glutathione include ultraviolet spectrum, vibrational spectrum, 1H and 13C nuclear magnetic resonance spectra, and mass spectrum. The profile also includes the compendial methods of analysis and the other methods of analysis that are reported in the literature. These other methods of e-analysis are: potentiometric, voltammetric, amperometric, spectrophotometric, specrtofluorometric, chemiluminescence, chromatographic and immunoassay methods. The stability of and several reviews on drug are also provided. More than 170 references are listed at the end this comprehensive profile on glutathione.

Dasatinib (Sprycel®), a second-generation TKI, has been shown to be effective as an anticancer drug in the treatment of patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia who are resistant or intolerant to imatinib. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of dasatinib showed a λmax of approximately 320-330nm, and IR spectroscopy principal peaks were observed at 3418 (NH), 3200 (OH), 1620 (CO), 1582 (CC and CN), 1513 (CHCH) cm(-1). Characteristic NH peaks were observed in nuclear magnetic resonance (NMR) spectroscopy at 11.47 and 9.88ppm. The molecular mass was observed at m/z=487.3((35)Cl) and 488.9((37)Cl) (molecular weight=487.15) and the fragmentation pattern was studied using ion trap mass spectrometry. In addition, different analytical methods for determination of dasatinib are also described in this review. Pharmacokinetically, dasatinib is rapidly absorbed after oral administration where the solubility is dependent on pH. Dasatinib extensively binds to human plasma proteins by approximately 96%. In leukemic patient, the calculated apparent volume of distribution for dasatinib was 2502L and the estimated elimination half-life was approximately 3-5h. Dasatinib is metabolized in humans markedly by CYP3A4 to active metabolites and by phase II drug-metabolizing enzymes, such as UDP glucuronosyltransferase. Dasatinib is mainly eliminated via the feces (85%), of which relatively small amount of dasatinib is excreted unchanged as intact drug (19%). Most of the adverse effects associated with dasatinib therapy are mild to moderate in severity and are usually reversible and manageable with appropriate intervention, such as cardiac failure, hypertension, and coronary artery disease.

Gefitinib (Iressa®) is a selective inhibitor of epidermal growth factor, a growth factor that plays a pivotal role in the control of cell growth, apoptosis, and angiogenesis. Gefitinib is clinically used for the treatment of chemoresistant non-small cell lung cancer patients. Gefitinib is freely soluble in dimethylsulphoxide but slightly soluble in methanol and ethanol. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of gefitinib showed a λmax of approximately 331nm, whereas IR spectroscopy principal peaks were observed at 3400cm(-1) (NH), 2956cm(-1) (CH2, CH, alkyl), 1625cm(-1) (CC, CN), 1500cm(-1) (HCCH, aryl), 1110cm(-1) (CO), 1028cm(-1) (CF). In addition, different analytical methods for determination of gefitinib are also described in this review. Pharmacokinetically, after oral administration, gefitinib is slowly absorbed with bioavailability of approximately 60% in human. Gefitinib is metabolized extensively in the liver into five metabolites by cytochrome P450s, primarily by CYP3A4 and to a lesser extent by CYP3A5 and CYP2D6. Gefitinib is eliminated mainly hepatically with total plasma clearance of 595mL/min after intravenous administration. Most of the adverse effects associated with gefitinib therapy are mild to moderate in severity and are usually reversible and manageable with appropriate intervention, such as diarrhea, dry skin, rash, nausea, and vomiting.

Imatinib (INN), marketed by Novartis as Gleevec (United States) or Glivec (Europe/Australia/Latin America), received Food & Drug Administration (FDA) approval in May 2001 and is a tyrosine kinase inhibitor used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia. Like all tyrosine kinase inhibitors, imatinib works by preventing a tyrosine kinase enzyme. Because the BCR-Abl tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, imatinib works as a form of targeted therapy-only cancer cells are killed through the drug's action. In this regard, imatinib was one of the first cancer therapies to show the potential for such targeted action and is often cited as a paradigm for research in cancer therapeutics. This study presents a comprehensive profile of imatinib, including detailed nomenclature, formulae, physico-chemical properties, methods of preparation, and methods of analysis (including compendial, electrochemical, spectroscopic, and chromatographic methods of analysis). Spectroscopic and spectrometric analyses include UV/vis spectroscopy, vibrational spectroscopy, nuclear magnetic resonance spectrometry ((1)H and (13)C NMR), and mass spectrometry. Chromatographic methods of analyses include electrophoresis, thin layer chromatography, and high-performance liquid chromatography. Preliminary stability investigations for imatinib have established the main degradation pathways, for example, oxidation to N-oxide under oxidative stress conditions. Stability was also carried out for the formulation by exposing to different temperatures 0°C, ambient temperature, and 40°C. No remarkable change was found in the drug content of formulation. This indicates that the drug was stable at the above optimized formulation. Stability studies under acidic and alkaline conditions have established the following main degradation products: α-(4-Methyl-1-piperazinyl)-3'-{[4-(3-pyridyl)-2-pyrimidinyl] amino}-p-tolu-p-toluid-ide methanesulfonate and 4-(4-methylpiperazin-1-ylmethyl)-benzoic acid. The main degradation products under oxidation conditions, that is, 4-[(4-methyl-4-oxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-enzamide, 4-[(4-methyl-1-oxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide, and 4-[(4-methyl-1,4-dioxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-enzamide. Clinical application studies for pharmacodynamics, pharmacokinetics, mechanism of action, and clinical uses of the drug were also presented. Each of the above stages includes appropriate figures and tables. More than 50 references were given as proof of the above-mentioned studies.

Azithromycin is an azalide, a subclass of macrolide antibiotics. It is derived from erythromycin, with a methyl-substituted nitrogen atom incorporated into the lactone ring, thus making the lactone ring 15-membered. It prevents bacteria from growing by interfering with their protein synthesis. It binds to the 50S subunit of the bacterial ribosome and thus inhibits translation of mRNA. Azithromycin is used to treat or prevent certain bacterial infections, most often those causing middle ear infections, strep throat, pneumonia, typhoid, bronchitis, and sinusitis. In recent years, it has been used primarily to prevent bacterial infections in infants and those with weaker immune systems. It is also effective against certain sexually transmitted infections, such as nongonococcal urethritis, chlamydia, and cervicitis. Recent studies have indicated it also to be effective against late-onset asthma, but these findings are controversial and not widely accepted. The present study gives a comprehensive profile of azithromycin, including detailed physico-chemical properties, nomenclature, formulae, methods of preparation, and methods of analysis (including compendial, electrochemical, spectroscopic, and chromatographic methods of analysis). Developed validated stability-indicating (HPLC and biodiffusion assay methods under accelerated acidic, alkaline, and oxidative conditions, in addition to effect of different types of light, temperature, and pH. Detailed clinical applications also presented (mechanism of action, ADME profile, clinical uses and doses, side effects, and drug interactions). Each of the above stages includes appropriate figures and tables. More than 80 references were given as a proof of the above-mentioned studies.

A comprehensive profile of moxifloxacin HCl with 198 references is reported. A full description including nomenclature, formulae, elemental analysis, and appearance is included. Methods of preparation for moxifloxacin HCl, its intermediates, and derivatives are fully described. In addition, the physical properties, analytical methods, stability, uses and applications, and pharmacology of moxifloxacin HCl are also discussed.