DOCSLIB.ORG

Quantitative Bioanalytical and Analytical Method Development of Dibenzazepine Derivative, Carbamazepine: a Review$

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Quantitative Bioanalytical and Analytical Method Development of Dibenzazepine Derivative, Carbamazepine: a Review$ View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Journal of Pharmaceutical Analysis 5 (2015) 213–222 HOSTED BY Contents lists available at ScienceDirect Journal of Pharmaceutical Analysis journal homepage: www.elsevier.com/locate/jpa www.sciencedirect.com Review Paper Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review$ Prasanna A. Datar n Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmacy, Narhe, Pune 411041, India article info abstract Article history: Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in Received 10 July 2014 physiological matrices. These methods could be applied to studies in areas of human clinical pharma- Received in revised form cology and toxicology. The major bioanalytical services are method development, method validation and 25 February 2015 sample analysis (method application). Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar Accepted 26 February 2015 electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quan- Available online 9 March 2015 titative analysis of carbamazepine in biological samples throughout all phases of clinical research and Keywords: quality control. The article incorporates various reported methods developed to help analysts in choosing Carbamazepine crucial parameters for new method development of carbamazepine and its derivatives and also enu- HPLC merates metabolites, and impurities reported so far. LC–MS/MS & 2015 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. All rights reserved. This is an HPTLC RP-UFLC open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Micellar electrokinetic chromatography Contents 1. Introduction........................................................................................................ 213 2. Mechanism of action . 214 3. GC................................................................................................................ 214 4. LC................................................................................................................ 215 5. HPLC.............................................................................................................. 217 5.1. API and metabolites. 217 5.2. Combination product. 218 5.3. Formulation . 219 6. HPTLC............................................................................................................. 219 7. UFLC..............................................................................................................220 8. MEKC.............................................................................................................220 9. Overview..........................................................................................................220 References.............................................................................................................220 1. Introduction enhance human health. Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physio- One of the major challenges faced by the pharmaceutical in- logical matrices, and could be applied to studies in area of human dustry today is finding new ways to increase productivity, de- clinical pharmacology and nonhuman pharmacology/toxicology crease costs whilst still ultimately developing new therapies that that involves evaluation and interpretation of bioequivalence, pharmacokinetic, and toxicokinetic studies. The major bioanaly- tical services include method development, method validation and ☆Peer review under responsibility of Xi'an Jiaotong University. n Tel.:þ91 9823161187. sample analysis (method application). E-mail addresses: [email protected], [email protected] Chromatographic methods such as gas chromatography (GC), http://dx.doi.org/10.1016/j.jpha.2015.02.005 2095-1779/& 2015 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 214 P.A. Datar / Journal of Pharmaceutical Analysis 5 (2015) 213–222 liquid chromatography–mass spectrometry (LC–MS), and high potentiation of synaptic transmission in the spinal cord [1]. performance liquid chromatography (HPLC) are commonly used in CBZ has a narrow therapeutic index and the relationship be- laboratories for the qualitative and quantitative analysis of drug tween dose and plasma concentrations of CBZ may be un- substances and biological samples throughout all the phases of predictable because of differences in genetics, age, gender, ab- method development of a drug in research and quality control. sorption, autoinduction and disease state between individuals. Further, method validation is carried out to ensure that the Also, the presence of numerous clinically significant drug inter- method developed was accurate, specific, reproducible and rugged actions supports the need of using therapeutic monitoring of CBZ over the specified range in which an analyte is analyzed. The as an essential tool in designing a safe and effective therapeutic present review covers the wide range of chromatographic tech- regimen for patients with epilepsy [2,3]. niques used in determination of carbamazepine (CBZ) and its CBZ (5H-dibenzo[b, f]azepine-5-carboxamide) is insoluble in congeners. It also incorporates records for simultaneous estima- water, soluble in alcohol, acetonitrile and acetone. CBZ is available tions performed using analytical techniques for CBZ or its con- in market with the brand names Carbamazepen, Carbatrol, Car- geners with other drug members, impurities and metabolites. bazepine, Carbelan and Epitol. Although CBZ is poorly soluble in CBZ is an anticonvulsant and mood-stabilizing drug used pri- aqueous media, it has a high oral bioavailability in humans [4]. marily in the treatment of epilepsy and bipolar disorder, as well as Metabolism occurs primarily in the liver via the cytochrome trigeminal neuralgia in old age patients. CBZ is indicated for the P-450 oxidase system, producing carbamazepine-l0, 11-epoxide treatment of partial seizures with simple or complex symptoma- (CBZ-EP) which is as active and may reach a level up to half that of tology (psychomotor, temporal lobe) and genaralized tonic-clonic CBZ. This is almost entirely converted to carbamazepine-trans-10, seizures (grand mal). CBZ is also used as a diuretic and antic- 11-dihydrodiol (CBZ–Di OH) by epoxide hydrolase before excretion holinergic. CBZ is a first-choice anticonvulsant because of its re- in the urine (Fig. 1). CBZ along with its metabolite was required to latively low psychological toxicity and the rarity of serious adverse be routinely measured, since there were patients for whom high effects. CBZ was discovered in 1953 by chemist Walter Schindler at concentrations of this metabolite could be responsible for other- J.R. Geigy AG in Basel, Switzerland. The drug was then synthesized wise unexplained toxicity. These toxicities may be due to de- in 1960 by chemist Schindler. Later, its anti-epileptic properties gradation products, metabolites present as impurities in the for- were discovered. In 1971, Drs. Takezaki and Hanaoka first used CBZ mulation, such impurities can be studied by forced degradation of to control mania in patients' refractory to antipsychotics. CBZ was CBZ under acid, base, oxidation, heat and photolytic conditions. first marketed as a drug to treat trigeminal neuralgia in 1962. It Degradation was observed in CBZ samples under stress conditions has been used as an anticonvulsant and antiepileptic in the UK like acid hydrolysis, photolysis and thermal exposure. Mild de- since 1965, and has been approved in the US since 1974. It is of- gradation was observed for alkaline hydrolysis and exposure to ficial in most of the pharmacopoeias. It is the drug of choice for oxidation by hydrogen peroxide [5,6]. many combination therapies and used in treatment of geriatric Identification and determination of unknown organic im- patients with multiple disease states. Method development for purities is the key to the production of high quality drug sub- such combination product formulations is still a challenge. stances. ICH guidelines indicate that impurities at or above 0.1% in the drug substance require identification [7]. Fig. 2 gives the list of pharmacopoeial impurities in CBZ reported in EP and BP. 2. Mechanism of action Various chromatographic methods such as GC, LC, LC–MS, HPLC, high performance thin layer chromatography (HPTLC), ultra- CBZ acts postsynaptically by limiting the ability of neurons to force liquid chromatography (UFLC) and micellar electrokinetic sustain high frequency repetitive firing of action potentials chromatography (MEKC) were used in laboratories for the quali- through enhancement of sodium channel inactivation. In addition tative and quantitative analysis of CBZ. to altering neuronal excitability, it may act presynaptically to block the release of neurotransmitter by blocking the presynaptic so- dium channels and the firing of action potentials, which in turn 3. GC decreases synaptic transmission. Pain relief is believed to be as- sociated with blockade of synaptic transmission in the trigeminal GC is a common type of chromatography used in analytical nucleus and seizure control with reduction of post-tetanic
Load more

Recommended publications
  • Alzheimer's Disease, a Decade of Treatment: What Have We Learned?
    A Critical Look at Medication Dementia: Alzheimer’s Disease Management Issues in Alzheimer’s Disease R.Ron Finley, B.S. Pharm., R.Ph,CGP Lecturer (Emeritus) and Assistant Clinical Professor, UCSF School of Pharmacy Clinical Pharmacist, UCSF Memory and Aging Center- Alzheimer’s Research Center Educational Objectives Disclosures 1. Define the role for cholinesterase inhibitors in the management of Alzheimer’s disease, Lewy Body dementia, Frontal Temporal Lobe dementia. Pfizer Speakers Bureau 2. Name three common side effects of atypical antipsychotic Forest Speakers Bureau drugs. Novartis Speakers Bureau 3. Construct a pharmacological treatment plan for a 77-year-old Rx Consultant Associate Editor patient diagnosed with Alzheimer’s disease and hallucinations. WindChime Consultant 4. Describe the role for antipsychotic, antidepressant, mood HGA HealthCare Consultant stabilizers and benzodiazepines in the management of psychiatric behavior problems related to Alzheimer’s disease. Elder Care Specialist Consultant 5. Cite three potential drug or disease interactions with cholinesterase inhibitors. The Many Faces of Dementia Risk Factors Linked to AD Alzheimer’s Disease Over 65 years of age and increases Vascular: Multi-infarct with age FrontalTemporal Lobe dementia ( FTD) and female Pick’s disease Head injury Lewy Body Dementia Progressive Supranuclear Palsy Factors associated with DM, HTN, CVD Corticobasal Degeneration Genetic: family history, specific Primary Progressive Aphasia chromosome mutations Huntington’s disease
    [Show full text]
  • Synthetic Drugs
    Comprehensive and Confident Identification of Narcotics, Steroids and Pharmaceuticals in Urine David E. Alonso1, Petra Gerhards2, Charles Lyle1 and Joe Binkley1 | 1LECO Corporation, St. Joseph, MI; 2LECO European LSCA Centre, Moenchengladbach, Germany Introduction Experimental Sample A (Traditional Drugs) Sample B (Synthetic Drugs) Monitoring of patients in hospitals and clinics has traditionally relied on Samples Representative Compounds Representative Compounds targeted methods of analysis. These screening methods are not Peak # Name Formula R.T. (s) Area Similarity Mass Delta (mDa) MA (ppm) 1 Creatinine ME C5H9N3O 210 1326229 800 -0.05 -0.43 • Obtained from a collaborating European hospital 3.5e6 3.0e6 Peak # Name Formula R.T. (s) Area Similarity 2 o-Ethynylaniline C8H7N 219 167436 893 0.07 0.63 1 Indole C8H7N 213 2744171 917 comprehensive and result in an incomplete picture of a patient’s 3 2-Methoxy-4-vinylphenol C H O 223 65764 805 0.11 0.73 52 patient monitoring samples 9 10 2 2 Creatinine ME C5H9N3O 216 613318 651 • 2.5e6 4 Nicotine C10H14N2 234 3249121 898 -0.21 -1.29 3 Pyridine, 2-(1-methyl-2-pyrrolidinyl)- C10H14N2 230 24869771 899 activities. Gas chromatography high resolution time-of-flight mass 3.0e6 5 Hordenin C10H15NO 274 949734 775 -0.14 -0.84 4 Parabanic acid, 1-methyl- C4H4N2O3 233 434278 764 Sample preparation 5 Cotinine C10H12N2O 336 27810908 918 • 6 Methylecgonine C10H17NO3 276 104640 835 -0.22 -1.1 spectrometry (GC-HRT) provides a fast and convenient method for 2.0e6 5 6 Caffeine C8H10N4O2 371 3753598 797 2.5e6 7 4-(3-Pyridyl-tetrahydrofuran-2-one C9H9NO2 313 93817 849 -0.11 -0.68 3,4 7 1-methyl-7H-xanthine C6H6N4O2 437 4868196 850 analysis of urine samples.
    [Show full text]
  • THE POSSIBLE ROLE of LEUKOCYTE-GENERATED Reactrve INTERMEDIATES in the DRUG-INDUCED Agrancnocytosis
    THE POSSIBLE ROLE OF LEUKOCYTE-GENERATED REACTrVE INTERMEDIATES IN THE DRUG-INDUCED AGRANCnOCYTOSIS Zhao Chao Liu A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Faculty of Pharmacy University of Toronto O Copyright by Zhao Chao Liu 1997 National Library Bibliothèque nationale (*m of Canada du Canada Acquisitions and Acquisitions et Bibliographic Services services bibliographiques 395 Wellington Street 395, rue Wellington Ottawa ON K1A ON4 Ottawa ON KIA ON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant a la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or seil reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la fome de microfiche/£ïlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. ABSTRACT Ticlopidine and clczapine are associated with relatively high incidences of agranulocytosis. 5-aminosalicylic acid (5-ASA) is an agent widely used in the treatment of inflammatory bowel disease. It has been demonstrated that many drugs associated with drug-induced agranulocytosis or dmg-induced lupus are oxidized by activated neutrophils to reactive intermediates, by the combination of myeloperoxidase (MPO), hydrogen peroxide and chloride ion, or simply by hypochlorous acid (HOCI).
    [Show full text]
  • Eslicarbazepine Acetate: a New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures
    Drugs R D DOI 10.1007/s40268-017-0197-5 REVIEW ARTICLE Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures 1 1 1 Graciana L. Galiana • Angela C. Gauthier • Richard H. Mattson Ó The Author(s) 2017. This article is an open access publication Abstract Eslicarbazepine acetate is a new anti-epileptic drug belonging to the dibenzazepine carboxamide family Key Points that is currently approved as adjunctive therapy and monotherapy for partial-onset (focal) seizures. The drug Eslicarbazepine acetate is an effective and safe enhances slow inactivation of voltage-gated sodium chan- treatment option for partial-onset seizures as nels and subsequently reduces the activity of rapidly firing adjunctive therapy and monotherapy. neurons. Eslicarbazepine acetate has few, but some, drug– drug interactions. It is a weak enzyme inducer and it Eslicarbazepine acetate improves upon its inhibits cytochrome P450 2C19, but it affects a smaller predecessors, carbamazepine and oxcarbazepine, by assortment of enzymes than carbamazepine. Clinical being available in a once-daily regimen, interacting studies using eslicarbazepine acetate as adjunctive treat- with a smaller range of drugs, and causing less side ment or monotherapy have demonstrated its efficacy in effects. patients with refractory or newly diagnosed focal seizures. The drug is generally well tolerated, and the most common side effects include dizziness, headache, and diplopia. One of the greatest strengths of eslicarbazepine acetate is its ability to be administered only once per day. Eslicar- 1 Introduction bazepine acetate has many advantages over older anti- epileptic drugs, and it should be strongly considered when Epilepsy is a common neurological disorder affecting over treating patients with partial-onset epilepsy.
    [Show full text]
  • Cambridgeshire and Peterborough Joint Prescribing Group MEDICINE REVIEW
    Cambridgeshire and Peterborough Joint Prescribing Group MEDICINE REVIEW Name of Medicine / Trimipramine (Surmontil®) Class (generic and brand) Licensed indication(s) Treatment of depressive illness, especially where sleep disturbance, anxiety or agitation are presenting symptoms. Sleep disturbance is controlled within 24 hours and true antidepressant action follows within 7 to 10 days. Licensed dose(s) Adults: For depression 50-75 mg/day initially increasing to 150-300 mg/day in divided doses or one dose at night. The maintenance dose is 75-150 mg/day. Elderly: 10-25 mg three times a day initially. The initial dose should be increased with caution under close supervision. Half the normal maintenance dose may be sufficient to produce a satisfactory clinical response. Children: Not recommended. Purpose of Document To review information currently available on this class of medicines, give guidance on potential use and assign a prescribing classification http://www.cambsphn.nhs.uk/CJPG/CurrentDrugClassificationTable.aspx Annual cost (FP10) 10mg three times daily: £6,991 25mg three times daily: £7,819 150mg daily: £7,410 300mg daily: £14,820 Alternative Treatment Options within Class Tricyclic Annual Cost CPCCG Formulary Classification Antidepressant (FP10) Amitriptyline (75mg) Formulary £36 Lofepramine (140mg) Formulary £146 Imipramine (75mg) Non-formulary £37 Clomipramine (75mg) Non-formulary £63 Trimipramine (75mg). TBC £7,819 Nortriptyline (75mg) Not Recommended (pain) £276 Doxepin (150mg) TBC £6,006 Dosulepin (75mg) Not Recommended (NICE DO NOT DO) £19 Dosages are based on possible maintenance dose and are not equivalent between medications Recommendation It is recommended to Cambridgeshire and Peterborough CCG JPG members and through them to local NHS organisations that the arrangements for use of trimipramine are in line with restrictions agreed locally for drugs designated as NOT RECOMMENDED:.
    [Show full text]
  • CBCS SYLLABUS) SUBJECT-BPH C 801 T-Pharmaceutical Chemistry III MULTIPLE CHOICE QUESTIONS: PRACTICE QUESTION BANK
    FINAL YEAR UNIVERSITY EXAMINATION 2019-2020 Final Year B.Pharm. Semester VIII (CBCS SYLLABUS) SUBJECT-BPH_C_801_T-Pharmaceutical Chemistry III MULTIPLE CHOICE QUESTIONS: PRACTICE QUESTION BANK SET-I Q. 1 Which is the correct IUPAC name for the following structure? A] 5-chloro-2-(methylamino)-5-phenyl-3H-1,4-benzodiazepine B] 7-chloro-2-(methylamino)-5-pyridinyl-3H-1,4-benzodiazepine-4-oxide C] 7-chloro-2-(ethylamino)-5-phenyl-3H-1,5-benzodiazepine D] 7-chloro-2-(methylamino)-5-phenyl-3H-1,4-benzodiazepine-4-oxide Q. 2 Which of the following is long acting sedative hypnotic? A] Diazepam B] Alprazolam C] Temazepam D] Imipramine Q. 3 Name of oxide derivative used as sedative hypnotic is A] Diazepam B] Chlordiazepoxide C]Nitazepam D] Ramelteon Q. 4 With respect to the following general structure which is the correctstatement ? A] X must be electropositive substituent for optimum activity B] X must be aromatic ring for optimum activity C] X must be electronegative substituent for optimum activity D] X must be H for optimum activity Q. 5 Which is the incorrect statement with respect to structure given in Q. 4 A] Ring C is ortho substituted with electron withdrawing group for optimum activity B] Ring C when para substituted increases activity C] Ring C is diortho substituted with electron withdrawing group for optimum activity D] Ring C when para substituted decreases activity Q. 6 What is the starting material for synthesis of Piroxicam (structure given below) A] B] C] D] Q. 7 Which one of the following is Cytokine inhibitor? A] Abatacept B] Fluoxetine C] Propranolol D]Aldosterone Q.
    [Show full text]
  • And Radiation Therapy Sensitizing Strategies in Tumours with Focus on Effects of Phenothiazines on Dna Damage Response Signalling
    From DEPARTMENT OF ONCOLOGY-PATHOLOGY Karolinska Institutet, Stockholm, Sweden ANALYSIS AND CHARACTERIZATION OF CHEMO- AND RADIATION THERAPY SENSITIZING STRATEGIES IN TUMOURS WITH FOCUS ON EFFECTS OF PHENOTHIAZINES ON DNA DAMAGE RESPONSE SIGNALLING Katarzyna Zielinska-Chomej Stockholm 2015 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by E-Print AB 2015 © Katarzyna Zielinska-Chomej, 2015 ISBN 978-91-7549-898-0 Analysis and characterization of chemo- and radiation therapy sensitizing strategies in tumours with focus on effects of phenothiazines on DNA damage response signalling THESIS FOR DOCTORAL DEGREE (Ph.D.) Dept of Oncology-Pathology, Cancer Center Karolinska (CCK) Lecture Hall, R8:00, Karolinska University Hospital, Stockholm Friday, the 16th of October, 2015, at 09:00 By Katarzyna Zielinska-Chomej Principal Supervisor: Opponent: Kristina Viktorsson, PhD Associate Prof Karin Roberg, MD, PhD Karolinska Institutet Linköping University Department of Oncology-Pathology Department of Clinical and Experimental Medicine Division of Otorhinolaryngology Co-supervisor(s): Petra Hååg, PhD Examination Board: Karolinska Institutet Associate Prof Marika Nestor, MD, PhD Department of Oncology-Pathology Uppsala University Department of Surgical Sciences, Otolaryngology and Head & Neck Surgery and Department of Professor Rolf Lewensohn, MD, PhD Immunology, Genetics and Pathology Karolinska Institutet Division of Biomedical Radiation Sciences Department of Oncology-Pathology
    [Show full text]
  • Clozapine-Induced Toxicity Via Induction of Oxidative Stress and Mitochondrial Dysfunction in Human Blood Lymphocytes and Protecting Role of L-Carnitine
    Original Research Article 2020;3(1):e9 Clozapine-induced Toxicity via Induction of Oxidative Stress and Mitochondrial Dysfunction in Human Blood Lymphocytes and Protecting role of L-Carnitine a b c,d a b* Ahmad Salimi , Farnaz Imani , Zhaleh Jamali , Negar Ahvar , Jalal Pourahmad a. Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran. b. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. c. Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. d. Department of Addiction Studies, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Article Info: Abstract: Received: September 2020 Clozapine is a useful antipsychotic drug but with serious, life threatening toxicity Accepted: September 2020 effects. The aim of this study is to assess the direct cytotoxicity effect of clozapine Published online: (CLZ) on human blood lymphocytes and investigate the protective effect of L‐carnitine October 2020 (LC) against clozapine‐induced cytotoxicity. Clozapine at 70 μM concentration induced cytotoxicity following 12 h. The Clozapine induced cytotoxicity was associated with intracellular reactive oxygen species (ROS) generation, mitochondrial * Corresponding Author: membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation, Jalal Pourahmad Email: and depletion of glutathione (GSH) and raising of oxidized glutathione (GSSG). We [email protected] showed that LC (1 mM) has a beneficial cytoprotective effect against clozapine- induced toxicity. Summery, clozapine causes organelles damages and triggers oxidative stress in lymphocytes. These data suggest that using of L‐carnitine could be useful for prevention and treatment of clozapine toxicity.
    [Show full text]
  • Microfilms International 300 N
    Synthesis and monoamine uptake inhibiting properties of perisubstituted tricyclic compounds Item Type text; Thesis-Reproduction (electronic) Authors Peters, Jennifer Margaret, 1956- Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 07/10/2021 13:32:03 Link to Item http://hdl.handle.net/10150/291828 INFORMATION TO USERS This reproduction was made from a copy of a document sent to us for microfilming. While the most advanced technology has been used to photograph and reproduce this document, the quality of the reproduction is heavily dependent upon the quality of the material submitted. The following explanation of techniques is provided to help clarify markings or notations which may appear on this reproduction. 1. The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting through an image and duplicating adjacent pages to assure complete continuity. 2. When an image on the film is obliterated with a round black mark, it is an indication of either blurred copy because of movement during exposure, duplicate copy, or copyrighted materials that should not have been filmed. For blurred pages, a good image of the page can be found in the adjacent frame.
    [Show full text]
  • Quick Release Pharmaceutical Compositions of Drug Substances
    Europäisches Patentamt *EP001109534B1* (19) European Patent Office Office européen des brevets (11) EP 1 109 534 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 9/16, A61K 9/20 of the grant of the patent: 12.02.2003 Bulletin 2003/07 (86) International application number: PCT/DK99/00480 (21) Application number: 99941418.8 (87) International publication number: (22) Date of filing: 10.09.1999 WO 00/015195 (23.03.2000 Gazette 2000/12) (54) QUICK RELEASE PHARMACEUTICAL COMPOSITIONS OF DRUG SUBSTANCES PHARMAZEUTISCHE ZUSAMMENSETZUNGEN MIT SCHNELLER FREISETZUNG VON WIRKSTOFFEN COMPOSITIONS A BASE DE SUBSTANCES MEDICAMENTEUSES A USAGE PHARMACEUTIQUE A LIBERATION RAPIDE (84) Designated Contracting States: • ITAI, Shigeru AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU Ageo-shi, Saitama 362-0046 (JP) MC NL PT SE Designated Extension States: (74) Representative: Plougmann & Vingtoft A/S AL LT LV MK RO SI Sundkrogsgade 9, P.O. Box 831 (30) Priority: 10.09.1998 DK 981143 2100 Copenhagen O (DK) (43) Date of publication of application: (56) References cited: 27.06.2001 Bulletin 2001/26 WO-A-95/32737 WO-A-96/14839 (73) Proprietor: NYCOMED DANMARK A/S • CHEMICAL ABSTRACTS, vol. 116, no. 10, 9 4000 Roskilde (DK) March 1992 (1992-03-09) Columbus, Ohio, US; abstract no. 91424, NEMOTO, MASAMI ET AL: (72) Inventors: "Solid preparations with accelerating • BERTELSEN, Poul absorption of oxicam-type anti-inflammatory DK-2720 Vanlose (DK) agents for internal use" XP002095848 & JP 03 • HANSEN, Nils, Gjerl v 240729 A (TAISHO PHARMACEUTICAL CO., DK-2000 Frederiksberg (DK) LTD., JAPAN) • RUCKENDORFER, Hermann A-4193 Reichenthal (AT) Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted.
    [Show full text]
  • Specific Adsorption Sites and Conditions Derived
    www.nature.com/scientificreports OPEN Specifc adsorption sites and conditions derived by thermal decomposition of activated carbons and adsorbed carbamazepine Daniel Dittmann 1,2*, Paul Eisentraut1, Caroline Goedecke1, Yosri Wiesner1, Martin Jekel2, Aki Sebastian Ruhl2,3 & Ulrike Braun1 The adsorption of organic micropollutants onto activated carbon is a favourable solution for the treatment of drinking water and wastewater. However, these adsorption processes are not sufciently understood to allow for the appropriate prediction of removal processes. In this study, thermogravimetric analysis, alongside evolved gas analysis, is proposed for the characterisation of micropollutants adsorbed on activated carbon. Varying amounts of carbamazepine were adsorbed onto three diferent activated carbons, which were subsequently dried, and their thermal decomposition mechanisms examined. The discovery of 55 diferent pyrolysis products allowed diferentiations to be made between specifc adsorption sites and conditions. However, the same adsorption mechanisms were found for all samples, which were enhanced by inorganic constituents and oxygen containing surface groups. Furthermore, increasing the loadings led to the evolution of more hydrated decomposition products, whilst parts of the carbamazepine molecules were also integrated into the carbon structure. It was also found that the chemical composition, especially the degree of dehydration of the activated carbon, plays an important role in the adsorption of carbamazepine. Hence, it is thought that the adsorption sites may have a higher adsorption energy for specifc adsorbates, when the activated carbon can then potentially increase its degree of graphitisation. Increasing amounts of pharmaceuticals enter the water bodies and are detected all over the world1–3. Many of them are persistent and may accumulate within water cycles4–6.
    [Show full text]
  • New Zealand Data Sheet
    1 PARNATE tranylcypromine film-coated tablets 10 mg New Zealand Data Sheet 1 PARNATE® (10 MG FILM-COATED TABLETS) PARNATE 10 mg film-coated tablets. 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Parnate 10 mg film-coated tablets: each tablet contains tranylcypromine sulfate equivalent to 10 mg of tranylcypromine. Excipients with known effect: each tablet contains sucrose 6 mg. For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Parnate 10 mg film-coated tablets contain "geranium rose" coloured, biconvex, film-coated tablets. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications Parnate is indicated for the treatment of symptoms of depressive illness especially where treatment with other types of anti-depressants has failed. It is not recommended for use in mild depressive states resulting from temporary situational difficulties. 4.2 Dose and method of administration Adults Begin with 20 mg a day given as 10 mg in the morning and 10 mg in the afternoon. If there is no satisfactory response after two weeks, add one more tablet at midday. Continue this dosage for at least a week. A dosage of 3 tablets a day should only be exceeded with caution. When a satisfactory response is established, dosage may be reduced to a maintenance level. Some patients will be maintained on 20 mg per day, some will need only 10 mg daily. If no improvement occurs, continued administration is unlikely to be beneficial. 1 2 PARNATE tranylcypromine film-coated tablets 10 mg When given together with a tranquilliser, the dosage of Parnate is not affected. When the medicine is given concurrently with electroconvulsive therapy, the recommended dosage is 10 mg twice a day during the series and 10 mg a day afterwards as maintenance therapy.
    [Show full text]