DOCSLIB.ORG

Development and Validation of Analytical Methods for the Determination of Some Drugs Used for the Treatment of Colon Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Development and Validation of Analytical Methods for the Determination of Some Drugs Used for the Treatment of Colon Diseases Development and validation of analytical methods for the determination of some drugs used for the treatment of colon diseases A thesis presented by Ahmed Adel Ibrahim Mohamed Othman B.Sc. Pharmacy and Biotechnology, Faculty of pharmacy, German University in Cairo 2011 Submitted for partial fulfillment for the degree of Master in Pharmaceutical Sciences (Pharmaceutical Chemistry) Under the Supervision of Prof. Dr. Ramzia Ismail Ibrahim El-Bagary Professor of Pharmaceutical Chemistry Faculty of Pharmacy, Cairo University Head of Pharmaceutical Chemistry Department, Faculty of Pharmacy-Future University Prof. Dr. Mohamed Mahmoud El-Kerdawy Professor of Medicinal Pharmaceutical Chemistry Faculty of Pharmacy, Mansoura University Dr. Ehab Farouk Hassan Elkady Assistant Professor of Pharmaceutical Chemistry Faculty of Pharmacy Cairo University Faculty of Pharmacy Cairo University 2017 English Abstract Development and validation of analytical methods for the determination of some drugs used for the treatment of colon diseases Different methods for the determination of some drugs used in the treatment of colon diseases, in bulk and dosage forms have been introduced in this thesis. The cited drugs are (balsalazide disodium, chlordiazepoxide, mebeverine hydrochloride, mesalazine, olsalazine sodium, and otilonium bromide). The chromatographic part includes a method for simultaneous determination of three commonly prescribed drugs used for treatment of inflammatory bowel diseases and was appled in ternary mixtures and dosage forms. Also, it involved simultaneous determination of olsalazine sodium and its degradation product 5-aminosalicylic acid (mesalazine) and was applied in binary mixtures and dosage form. Finally in this part, an HPLC method was introduced for the simultaneous determination of otilonium bromide and its degradation product 4- aminobenzioc acid and was applied in dosage form. On the other hand, spectrophotometric part includes simultaneous spectrophotometric determination of mebeverine hydrochloride and chlordiazepoxide in bulk and pharmaceutical dosage form using three chemometric techniques, classical least square(CLS), principal component regression (PCR) and partial least squares (PLS). Also, it involved simultaneous determination spectrophotometric determination of otilonium bromide with its degradation products 4- aminobenzoic acid and salicylic acid using CLS, PCR and PLS chemometric techniques. Also, this part includes derivative spectrophotometric methods in which a validated spectrophotometric method was introduced for simultaneous determination of mebeverine hydrochloride and chlordiazepoxide in binary mixture and pharmaceutical preparations using second derivative method for determination of mebeverine hydrochloride and first derivative method for determination of chlordiazepoxide and other validated fourth derivative spectrophotometric method used for simultaneous determination otilonium bromide with its degradation products 4-aminobenzioc acid and salicylic acid. Statistical analysis was carried out for comparing results of the proposed methods with the reference methods exhibiting good values and revealing insignificant difference. Keywords: balsalazide disodium, chlordiazepoxide, mebeverine hydrochloride, mesalazine, olsalazine sodium, otilonium bromide, HPLC, Chemometric techniques, derivative spectrophotometric methods, pharmaceutical preparations. I-1- General introduction Colon diseases include inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and colonic cancer. The chief types of inflammatory bowel disease are Crohn's disease (CD) and Ulcerative colitis (UC). Inflammatory bowel diseases fall into the class of autoimmune diseases, in which the body's own immune system attacks elements of the digestive system[1].The difference between CD and UC is the location and nature of the inflammatory changes. CD can affect any part of the gastrointestinal tract, from mouth to anus, although a majority of the cases start in the terminal ileum. UC, in contrast, is restricted to the colon and the rectum[2]. Microscopically, UC is restricted to the mucosa (epithelial lining of the gut), while CD affects the full thickness of the bowel wall ("transmural lesions"). Lastly, CD and UC present with extra-intestinal manifestations (such as liver problems, arthritis, skin manifestations and eye problems) in different proportions[2]. In spite of CD and UC being very different diseases, both may be present with any of the following symptoms: abdominal pain, vomiting, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease [3, 4]. Associated complaints or diseases include arthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and non-thyroidal illness syndrome [5]. Associations with deep vein thrombosis [6] and bronchiolitis obliterans organizing pneumonia have also been reported [7]. Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions. Colon associated diseases such as nervous colon or, IBS which is a group of symptoms including abdominal pain and changes in the pattern of bowel movements without any evidence of underlying damage [8]. These symptoms occur over a long time, often years [9]. There are three types of IBS: a- IBS with Constipation (IBS-C): this comes with stomach pain and discomfort, bloating, abnormally delayed or infrequent bowel movement, or lumpy/hard stool. b- IBS with Diarrhea (IBS-D): this comes with stomach pain and discomfort, an urgent need to move your bowels, abnormally frequent bowel movements, or loose/watery stool. c- IBS with alternating constipation and diarrhea [10]. Disorders such as anxiety, major depression, and chronic fatigue syndrome, are common among people with IBS [8, 11]. The causes of IBS are not clear. Theories include gut–brain axis problems, small intestinal bacterial overgrowth, genetic factors, food sensitivity, and gut motility problems [9]. Onset may be triggered by an intestinal infection [12], or stressful life event [13]. IBS is a functional gastrointestinal disorder [8]. Ulcerative colitis (UC) is a chronic inflammatory disorder of colon. This inflammation may be limited to the left-hand side of the colon or extend to entire colon. Colon related pathologies range in seriousness from constipation and diarrhea to the incapacitating inflammatory bowel diseases through to colon cancer, the third most widespread form of cancer in both women and men. Carcinoma of the colon afflicts patients with ulcerative colitis 7–30 times more frequently than it does the general population. The risk of colon cancer in ulcerative colitis is related to two factors: (1) duration of the colitis, and (2) extent of colonic involvement. The colonic malignancy associated with ulcerative colitis is generally an adenocarcinoma evenly scattered throughout the colon [14]. Figure (1): Anatomic distribution of Crohn’s disease and Ulcerative colitis [15] . 1-Some important drug classes of colon diseases Drugs used for treatment of IBS a-Muscarinic antagonists One of the most important compounds in this class is hyoscine, it acts on the relaxation of the smooth muscles of the gut [16], it is used as antispasmodic to reduce the activity of the gastrointestinal tract. Dicyclomine and hyoscyamine are also antispasmodics in IBS [16]. These medications can be given as an oral formulation or a sublingual tablet, and be dosed on an as-needed or regular basis. Many patients benefit by taking the medication before meals. A number of these agents are presented in Table (1). Mebeverine hydrochloride acts directly on the gut muscles at the cellular level to relax them [17]. This relieves painful muscle spasms of the gut without affecting its normal motility. Mebeverine possess a phenylethylamine moiety which affects the colonic motility as well as gastric motility and has been used in treatment of IBS [18]. Table (1). Table (1): Most commonly used Antispasmodics. Drug Structure Trade name Dicyclomine HCl .HCl Spasmorest® Hyoscine N- Buscopan® Butylbromide Mebeverine Coloverin SR® Otilonium bromide Spasmomen® b-Calcium antagonists Pinaverium Bromide belongs to this class which inhibits the calcium influx by blocking the voltage dependent calcium channels at the smooth muscle cell level. It is selective for the intestinal smooth muscle [19]. It is used to treat IBS by relieving the symptoms of abdominal pain, bowel disturbances and intestinal discomfort [20]. Structure activity relationship (SAR) study reveals that quaternary ammonium derivatives such as pinaverium bromide have been discovered and developed as potent spasmolytic of the gastrointestinal tract. Table (2). Table (2): Most commonly used Calcium antagonists. Drug Structure Trade name Pinaverium Bromide Spascolon® c-Adjuvant therapy for IBS Although many drugs are available to treat the symptoms of irritable bowel syndrome, these drugs do not cure the condition. They are primarily used to relieve symptoms. The choice among these medications depends in part upon whether the patients have diarrhea, anxiety or pain-predominant irritable bowel syndrome such as: 1-Anti-anxiety drugs Anti-anxiety drugs reduce anxiety. Chlordiazepoxide (Librax®), Diazepam (Valium®), lorazepam (Ativan®), and clonazepam (Klonopin®) belong to this class of drugs. Anti-anxiety drugs are occasionally prescribed for people with short-term
Load more

Recommended publications
  • Isopropamide Iodide
    www.chemicalland21.com ISOPROPAMIDE IODIDE SYNONYMS (3-Carbamoyl-3,3-diphenylpropyl)diisopropylmethylammonium iodide; 2,2-Diphenyl-4- diisopropylaminobutyramide methiodide; 4-(Diisopropylamino)-2,2-diphenylbutyramide methiodide; gamma-(Aminocarbonyl)-N-methyl-N,N-bis(1-methylethyl)-gamma-phenylbenzenepropanaminium iodide; Iodure d'isopropamide; Ioduro de isopropamida; Isopropamide ioduro; Isopropamidi iodidum; Isoproponum iodide; PRODUCT IDENTIFICATION CAS RN 71-81-8 EINECS RN 200-766-8 FORMULA C23H33IN2O MOL WEIGHT 480.43 PHYSICAL AND CHEMICAL PROPERTIES PHYSICAL STATE white to off-white powder MELTING POINT 199 C BOILING POINT DENSITY SOLUBILITY IN WATER pH VAPOR DENSITY REFRACTIVE INDEX FLASH POINT GENERAL DESCRIPTION Isopropamide is a long-acting anticholinergic and antimuscarinic drug of quaternary ammonium structure. It is used in the form of the iodide, (also bromide or chloride) to treat peptic ulcer and to suppress gastric secretion other gastrointestinal disorders. Brands of Isopropamide drugs: Darbid Dipramide Isamide Marygin-M Piaccamide Priamide Priazimide Sanulcin Tyrimide Quaternary ammonium anticholinergics (Synthetic) ATC Code Product CAS RN. A03AB01 Benzilonium bromide 1050-48-2 A03AB02 Glycopyrrolate 596-51-0 A03AB03 Oxyphenonium 14214-84-7 A03AB04 Penthienate 22064-27-3 A03AB05 Propantheline 50-34-0 A03AB06 Otilonium bromide 26095-59-0 A03AB07 Methantheline 5818-17-7 Please mail us if you want to sell your product or need to buy some products) www.chemicalland21.com ISOPROPAMIDE IODIDE A03AB08 Tridihexethyl 60-49-1 A03AB09 Isopropamide 7492-32-2 A03AB10 Hexocyclium 6004-98-4 A03AB11 Poldine 596-50-9 A03AB12 Mepenzolic acid 25990-43-6 A03AB13 Bevonium 33371-53-8 A03AB14 Pipenzolate 13473-38-6 A03AB15 Diphemanil methylsulfate 62-97-5 A03AB16 (2-Benzhydryloxyethyl)diethyl-methylammonium iodide A03AB17 Tiemonium iodide 144-12-7 A03AB18 Prifinium bromide 4630-95-9 A03AB19 Timepidium bromide 35035-05-3 A03AB21 Fenpiverinium bromide 125-60-0 03AB53 Oxyphenonium, combinations STABILITY AND REACTIVITY STABILITY Stable under normal conditions.
    [Show full text]
  • The National Drugs List
    ^ ^ ^ ^ ^[ ^ The National Drugs List Of Syrian Arab Republic Sexth Edition 2006 ! " # "$ % &'() " # * +$, -. / & 0 /+12 3 4" 5 "$ . "$ 67"5,) 0 " /! !2 4? @ % 88 9 3: " # "$ ;+<=2 – G# H H2 I) – 6( – 65 : A B C "5 : , D )* . J!* HK"3 H"$ T ) 4 B K<) +$ LMA N O 3 4P<B &Q / RS ) H< C4VH /430 / 1988 V W* < C A GQ ") 4V / 1000 / C4VH /820 / 2001 V XX K<# C ,V /500 / 1992 V "!X V /946 / 2004 V Z < C V /914 / 2003 V ) < ] +$, [2 / ,) @# @ S%Q2 J"= [ &<\ @ +$ LMA 1 O \ . S X '( ^ & M_ `AB @ &' 3 4" + @ V= 4 )\ " : N " # "$ 6 ) G" 3Q + a C G /<"B d3: C K7 e , fM 4 Q b"$ " < $\ c"7: 5) G . HHH3Q J # Hg ' V"h 6< G* H5 !" # $%" & $' ,* ( )* + 2 ا اوا ادو +% 5 j 2 i1 6 B J' 6<X " 6"[ i2 "$ "< * i3 10 6 i4 11 6! ^ i5 13 6<X "!# * i6 15 7 G!, 6 - k 24"$d dl ?K V *4V h 63[46 ' i8 19 Adl 20 "( 2 i9 20 G Q) 6 i10 20 a 6 m[, 6 i11 21 ?K V $n i12 21 "% * i13 23 b+ 6 i14 23 oe C * i15 24 !, 2 6\ i16 25 C V pq * i17 26 ( S 6) 1, ++ &"r i19 3 +% 27 G 6 ""% i19 28 ^ Ks 2 i20 31 % Ks 2 i21 32 s * i22 35 " " * i23 37 "$ * i24 38 6" i25 39 V t h Gu* v!* 2 i26 39 ( 2 i27 40 B w< Ks 2 i28 40 d C &"r i29 42 "' 6 i30 42 " * i31 42 ":< * i32 5 ./ 0" -33 4 : ANAESTHETICS $ 1 2 -1 :GENERAL ANAESTHETICS AND OXYGEN 4 $1 2 2- ATRACURIUM BESYLATE DROPERIDOL ETHER FENTANYL HALOTHANE ISOFLURANE KETAMINE HCL NITROUS OXIDE OXYGEN PROPOFOL REMIFENTANIL SEVOFLURANE SUFENTANIL THIOPENTAL :LOCAL ANAESTHETICS !67$1 2 -5 AMYLEINE HCL=AMYLOCAINE ARTICAINE BENZOCAINE BUPIVACAINE CINCHOCAINE LIDOCAINE MEPIVACAINE OXETHAZAINE PRAMOXINE PRILOCAINE PREOPERATIVE MEDICATION & SEDATION FOR 9*: ;< " 2 -8 : : SHORT -TERM PROCEDURES ATROPINE DIAZEPAM INJ.
    [Show full text]
  • WITHOUTUS010307409B2 (12 ) United States Patent ( 10 ) Patent No
    WITHOUTUS010307409B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 307 ,409 B2 Chase et al. (45 ) Date of Patent: Jun . 4 , 2019 ( 54 ) MUSCARINIC COMBINATIONS AND THEIR (52 ) U . S . CI. USE FOR COMBATING CPC . .. .. A61K 31/ 4439 (2013 . 01 ) ; A61K 9 /0056 HYPOCHOLINERGIC DISORDERS OF THE (2013 . 01 ) ; A61K 9 / 7023 ( 2013 . 01 ) ; A61K CENTRAL NERVOUS SYSTEM 31 / 166 ( 2013 . 01 ) ; A61K 31 / 216 ( 2013 . 01 ) ; A61K 31 /4178 ( 2013 .01 ) ; A61K 31/ 439 (71 ) Applicant: Chase Pharmaceuticals Corporation , ( 2013 .01 ) ; A61K 31 /44 (2013 . 01 ) ; A61K Washington , DC (US ) 31/ 454 (2013 .01 ) ; A61K 31/ 4725 ( 2013 .01 ) ; A61K 31 /517 (2013 .01 ) ; A61K 45 / 06 ( 72 ) Inventors : Thomas N . Chase , Washington , DC (2013 . 01 ) (US ) ; Kathleen E . Clarence -Smith , ( 58 ) Field of Classification Search Washington , DC (US ) CPC .. A61K 31/ 167 ; A61K 31/ 216 ; A61K 31/ 439 ; A61K 31 /454 ; A61K 31 /4439 ; A61K (73 ) Assignee : Chase Pharmaceuticals Corporation , 31 /4175 ; A61K 31 /4725 Washington , DC (US ) See application file for complete search history. ( * ) Notice : Subject to any disclaimer, the term of this (56 ) References Cited patent is extended or adjusted under 35 U . S . C . 154 (b ) by 0 days . U . S . PATENT DOCUMENTS 5 ,534 ,520 A 7 / 1996 Fisher et al. ( 21) Appl . No. : 15 /260 , 996 2008 /0306103 Al 12 /2008 Fisher et al. 2011/ 0021503 A1* 1/ 2011 Chase . .. A61K 31/ 27 ( 22 ) Filed : Sep . 9 , 2016 514 / 215 2011/ 0071135 A1 * 3 / 2011 Chase . .. .. .. A61K 31/ 166 (65 ) Prior Publication Data 514 / 215 2011 /0245294 Al 10 / 2011 Paborji et al.
    [Show full text]
  • Muscarinic Acetylcholine Receptor
    mAChR Muscarinic acetylcholine receptor mAChRs (muscarinic acetylcholine receptors) are acetylcholine receptors that form G protein-receptor complexes in the cell membranes of certainneurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibersin the parasympathetic nervous system. mAChRs are named as such because they are more sensitive to muscarine than to nicotine. Their counterparts are nicotinic acetylcholine receptors (nAChRs), receptor ion channels that are also important in the autonomic nervous system. Many drugs and other substances (for example pilocarpineand scopolamine) manipulate these two distinct receptors by acting as selective agonists or antagonists. Acetylcholine (ACh) is a neurotransmitter found extensively in the brain and the autonomic ganglia. www.MedChemExpress.com 1 mAChR Inhibitors & Modulators (+)-Cevimeline hydrochloride hemihydrate (-)-Cevimeline hydrochloride hemihydrate Cat. No.: HY-76772A Cat. No.: HY-76772B Bioactivity: Cevimeline hydrochloride hemihydrate, a novel muscarinic Bioactivity: Cevimeline hydrochloride hemihydrate, a novel muscarinic receptor agonist, is a candidate therapeutic drug for receptor agonist, is a candidate therapeutic drug for xerostomia in Sjogren's syndrome. IC50 value: Target: mAChR xerostomia in Sjogren's syndrome. IC50 value: Target: mAChR The general pharmacol. properties of this drug on the The general pharmacol. properties of this drug on the gastrointestinal, urinary, and reproductive systems and other… gastrointestinal, urinary, and reproductive systems and other… Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 1 mg, 5 mg 1 mg, 5 mg AC260584 Aclidinium Bromide Cat. No.: HY-100336 (LAS 34273; LAS-W 330) Cat.
    [Show full text]
  • The Role of Antispasmodics in Managing Irritable Bowel Syndrome
    DOI: https://doi.org/10.22516/25007440.309 Review articles The role of antispasmodics in managing irritable bowel syndrome Valeria Atenea Costa Barney,1* Alan Felipe Ovalle Hernández.1 1 Internal Medicine and Gastroenterology specialist Abstract in San Ignacio University Hospital, Pontificia Universidad Javeriana, Bogotá, Colombia. Although antispasmodics are the cornerstone of treating irritable bowel syndrome, there are a number of an- tispasmodic medications currently available in Colombia. Since they are frequently used to treat this disease, *Correspondence: [email protected] we consider an evaluation of them to be important. ......................................... Received: 26/10/18 Keywords Accepted: 11/02/19 Antispasmodic, irritable bowel syndrome, pinaverium bromide, otilonium bromide, Mebeverin, trimebutine. INTRODUCTION consistency. The criteria must be met for three consecutive months prior to diagnosis and symptoms must have started Irritable bowel syndrome (IBS) is one of the most fre- a minimum of six months before diagnosis. (3, 4) quent chronic gastrointestinal functional disorders. It is There are no known structural or anatomical explanations characterized by recurrent abdominal pain associated with of the pathophysiology of IBS and its exact cause remains changes in the rhythm of bowel movements with either or unknown. Nevertheless, several mechanisms have been both constipation and diarrhea. Swelling and bloating are proposed. Altered gastrointestinal motility may contribute frequent occurrences. (1) to changes in bowel habits reported by some patients, and a IBS is divided into two subtypes: predominance of cons- combination of smooth muscle spasms, visceral hypersen- tipation (20-30% of patients) and predominance of dia- sitivity and abnormalities of central pain processing may rrhea (20-30% of patients).
    [Show full text]
  • NVA237 / Glycopyrronium Bromide Multinational, Multi-Database Drug
    Quantitative Safety & Epidemiology NVA237 / Glycopyrronium bromide Non-interventional Final Study Report NVA237A2401T Multinational, multi-database drug utilization study of inhaled NVA237 in Europe Author Document Status Final Date of final version 28 April 2016 of the study report EU PAS register ENCEPP/SDPP/4845 number Property of Novartis Confidential May not be used, divulged, published or otherwise disclosed without the consent of Novartis NIS Report Template Version 2.0 August-13-2014 Novartis Confidential Page 2 Non-interventional study report NVA237A/Seebri® Breezhaler®/CNVA237A2401T PASS information Title Multinational, multi-database drug utilization study of inhaled NVA237 in Europe –Final Study Report Version identifier of the Version 1.0 final study report Date of last version of 28 April 2016 the final study report EU PAS register number ENCEPP/SDPP/4845 Active substance Glycopyrronium bromide (R03BB06) Medicinal product Seebri®Breezhaler® / Tovanor®Breezhaler® / Enurev®Breezhaler® Product reference NVA237 Procedure number SeebriBreezhaler: EMEA/H/C/0002430 TovanorBreezhaler: EMEA/H/C/0002690 EnurevBreezhaler: EMEA/H/C0002691 Marketing authorization Novartis Europharm Ltd holder Frimley Business Park Camberley GU16 7SR United Kingdom Joint PASS No Research question and In the context of the NVA237 marketing authorization objectives application, the Committee for Medicinal Products for Human Use (CHMP) recommended conditions for marketing authorization and product information and suggested to conduct a post-authorization
    [Show full text]
  • A Four-Country Comparison of Healthcare Systems, Implementation
    Neurogastroenterology & Motility Neurogastroenterol Motil (2014) 26, 1368–1385 doi: 10.1111/nmo.12402 REVIEW ARTICLE A four-country comparison of healthcare systems, implementation of diagnostic criteria, and treatment availability for functional gastrointestinal disorders A report of the Rome Foundation Working Team on cross-cultural, multinational research M. SCHMULSON,* E. CORAZZIARI,† U. C. GHOSHAL,‡ S.-J. MYUNG,§ C. D. GERSON,¶ E. M. M. QUIGLEY,** K.-A. GWEE†† & A. D. SPERBER‡‡ *Laboratorio de Hıgado, Pancreas y Motilidad (HIPAM)-Department of Experimental Medicine, Faculty of Medicine-Universidad Nacional Autonoma de Mexico (UNAM). Hospital General de Mexico, Mexico City, Mexico †Gastroenterologia A, Department of Internal Medicine and Medical Specialties, University La Sapienza, Rome, Italy ‡Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India §Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea ¶Division of Gastroenterology, Mount Sinai School of Medicine, New York, NY, USA **Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA ††Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ‡‡Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Key Messages • This report identified seven key issues related to healthcare provision that may impact how patients with FGIDs are investigated, diagnosed and managed. • Variations in healthcare provision around the world in patients with FGIDs have not been reviewed. • We compared four countries that are geographically and culturally diverse, and exhibit differences in the healthcare coverage provided to their population: Italy, South Korea, India and Mexico. • Since there is a paucity of publications relating to the issues covered in this report, some of the findings are based on the authors’ personal perspectives, press reports and other published sources.
    [Show full text]
  • TITLE: Trimebutine Maleate and Pinaverium Bromide for Irritable Bowel Syndrome: a Review of the Clinical Effectiveness, Safety and Guidelines
    TITLE: Trimebutine Maleate and Pinaverium Bromide for Irritable Bowel Syndrome: A Review of the Clinical Effectiveness, Safety and Guidelines DATE: 30 November 2015 CONTEXT AND POLICY ISSUES Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel movement consistency and frequency resulting in constipation or diarrhea.1,2 It is a functional disorder and not an organic disease.2 According to the Rome III diagnostic criteria, IBS is defined as recurrent abdominal pain or discomfort for at least three days per month in the last three months and with two or more of the following: improvement with defecation, onset associated with a change in frequency of stool, or onset associated with a change in form (appearance) of stool.2,3 There are three main subtypes of IBS: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed IBS (IBS-M).2 Hard or lumpy stool with ≥25% of bowel movements and loose or watery stool with < 25% of bowel movements is indicative of IBS-C. Loose or watery stool with ≥25% of bowel movements and hard or lumpy stool with < 25% of bowel movements is indicative of IBS-D. Hard or lumpy stool with ≥25% of bowel movements and loose or watery stool with ≥ 25% of bowel movements is indicative IBS-M. 2 The reported prevalence estimates of IBS vary widely. Some of this variation may result from differences in the clinical setting and the criteria used for diagnosis.1 There is no gold standard for diagnosing IBS.1 Criteria for diagnosing IBS
    [Show full text]
  • Government Gazette
    Government Gazette REPUBLIC OF SOUTH AFRICA Regulation Gazette No. 7636 Vol. 454 Pretoria 10 April 2003 No. 24727 AIDS HELPLINE: 0800-0123-22 Prevention is the cure I STAATSKOERANT, 10 APRIL 2003 No. 24727 3 GOVERNMENT NOTICES GOEWERMENTSKENNISGEWINGS DEPARTMENT OF HEALTH DEPARTEMENT VAN GESONDHEID NO. R. 509 10 April 2003 SCHEDULES The Minister of Health has, in terms of section 22A(2) of the Medicines and Related Substances Act, 1965 (Act No. 101 of 1965), on the recommendation of the Medicines Control Council, made the Schedulesin the Schedule SCHEDULE I In these Schedules, "the Act" meansthe Medicines and Related SubstancesAct, 1965 (Act No. 101 of 1965) SCHEDULE 0 (a) All substancesreferred to in thisSchedule are excluded when specifically packed, labelled and usedfor - (i) industrialpurposes including the manufacture or compounding of consumer items or products which have no pharmacological oraction medicinal purpose, which are intended to be ingested by man or animals as food, or applied to the body as a cosmetic, and which are approved for such use in terms of the Foodstuffs, Cosmetics and Disinfectants Act, 1972 (Act No. 54 of 1972) or registeredin terms of theFertilizers, Farm Feeds, Agricultural Remedies and Stock Remedies Act, 1947 (Act No. 36 of 1947); and (ii)analytical laboratory purposes. (b) All substances referred to in this Schedule include the following: 4 No. 24727 GOVERNMENT GAZETTE, 10 APRIL 2003 (i) The saltsand esters of suchsub2ances,+vhere the existence of such salts and esters is possible; and (ii) All preparationsand mixtures of suchsubstances where such preparations and mixtures arenot expressly excluded. This Schedule includesall substances subject to registration in termsof the Act and which are not listed in anyof the other Schedules.
    [Show full text]
  • Antiallergics Loratadinep Allergy √ JP DMF Antiarrhythmics
    Jun. 2020 API THERAPEUTIC AREA PRODUCT INDICATION CEP/DMF MICRONIZED Antiallergics LoratadineP Allergy √ JP DMF Antiarrhythmics DronedaroneP Atrial fibrillation & general arrhythmia DMF Arformoterol tartrateP polymorph A and D COPD US-CN DMF Formoterol fumarate Asthma and COPD √ CEP/US-JP-KR-CN DMF Glycopyrronium bromideP COPD √ CEP/ US-CN DMF Antiasthmatics, COPD and Indacaterol maleateP Asthma and COPD √ EU/US DMF respiratory diseases Montelukast sodiumP Asthma, allergic & seasonal rhinitis EU-JP DMF Salmeterol xinafoateP Asthma and COPD √ CEP/ US-CN-KR DMF Tiotropium Bromide COPD √ CEP/US-CN DMF Granisetron baseP Emesis US DMF Granisetron hydrochlorideP Emesis CEP/ US-JP-KR DMF Antiemetics Ondansetron baseP Emesis √ EU-US DMF Ondansetron hydrochlorideP Emesis √ CEP/US DMF Antifungals FluconazoleP Antifungal CEP/US-KR DMF CarvedilolP Hypertension, angina, heart failure JP DMF Enalapril maleateP Hypertension CEP/KR DMF Antihipertensive Imidapril Hypertension EU DMF Nitrendipine Hypertension √ CEP/DMF Eletriptan HBrP Migraine √ JP DMF Antimigrainics Rizatriptan benzoateP Migraine √ EU-US DMF ZolmitriptanP Migraine √ EU-US DMF Asenapine maleateP Schizophrenia and acute mania √ OlanzapineP Schizophrenia, psychosis EU-US- DMF Antipsychotics Quetiapine hemifumarate P Schizophrenia, psychosis JP-KR DMF RisperidoneP Schizophrenia, psychosis √ CEP/US-KR DMF Prasugrel baseP Prophylaxis and therapy of thrombosis EU DMF Antithrombotics Rivaroxaban Thrombosis. Stroke DMF Spasmolytic Otilonium bromide Irritable bowel syndrome EU DMF CEP = Products with Certificate of Suitability / P = Patent applications/granted patents owned by Neuraxpharm Listed products protected by valid patents are developed solely for purposes related to the development, preparation and submission of information to obtain a Marketing Authorization. In particular these products are under development for uses related to the activities stated in Art.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen Et Al
    US009283192B2 (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen et al. (45) Date of Patent: Mar. 15, 2016 (54) DELAYED PROLONGED DRUG DELIVERY 2009. O1553.58 A1 6/2009 Diaz et al. 2009,02976O1 A1 12/2009 Vergnault et al. 2010.0040557 A1 2/2010 Keet al. (75) Inventors: Alexander Mullen, Glasgow (GB); 2013, OO17262 A1 1/2013 Mullen et al. Howard Stevens, Glasgow (GB); Sarah 2013/0022676 A1 1/2013 Mullen et al. Eccleston, Scotstoun (GB) FOREIGN PATENT DOCUMENTS (73) Assignee: UNIVERSITY OF STRATHCLYDE, Glasgow (GB) EP O 546593 A1 6, 1993 EP 1064937 1, 2001 EP 1607 O92 A1 12/2005 (*) Notice: Subject to any disclaimer, the term of this EP 2098 250 A1 9, 2009 patent is extended or adjusted under 35 JP HO5-194188 A 8, 1993 U.S.C. 154(b) by 0 days. JP 2001-515854. A 9, 2001 JP 2001-322927 A 11, 2001 JP 2003-503340 A 1, 2003 (21) Appl. No.: 131582,926 JP 2004-300148 A 10, 2004 JP 2005-508326 A 3, 2005 (22) PCT Filed: Mar. 4, 2011 JP 2005-508327 A 3, 2005 JP 2005-508328 A 3, 2005 (86). PCT No.: PCT/GB2O11AOOO3O7 JP 2005-510477 A 4/2005 JP 2008-517970 A 5, 2008 JP 2009-514989 4/2009 S371 (c)(1), WO WO99,12524 A1 3, 1999 (2), (4) Date: Oct. 2, 2012 WO WOO1 OO181 A2 1, 2001 WO WOO3,O266.15 A2 4/2003 (87) PCT Pub. No.: WO2011/107750 WO WOO3,O26625 A1 4/2003 WO WO 03/026626 A2 4/2003 PCT Pub.
    [Show full text]
  • Surveillance Review Proposal PDF 387 KB
    National Institute for Health and Care Excellence Surveillance programme Surveillance proposal consultation document Irritable bowel syndrome NICE guideline CG61 – 8-year surveillance review Background information Guideline issue date: February 2008 3-year review (no update)* 6-year review (yes to update) *Although the 3-year review decision was no update, the findings were subsequently used to pilot the NICE’s rapid update process. Surveillance proposal for consultation We will not update the guideline at this time. Reason for the proposal New evidence We found 105 new studies in a search for randomised controlled trials (RCTs) and systematic reviews published between 01 September 2013 and 18 July 2016. We also considered studies identified by members of the guideline committee who originally worked on this guideline. Evidence identified in previous surveillance 3 years and 6 years after publication of the guideline was also considered. This included 52 studies identified by search. From all sources, 157 studies were considered to be relevant to the guideline. Surveillance proposal consultation document for Irritable bowel syndrome (2008) NICE guideline CG61 1 of 44 This included new evidence that is consistent with current recommendations on: diagnosis of irritable bowel syndrome (IBS) dietary interventions physical activity interventions drug treatments (antispasmodics, laxatives, anti-motility agents and antidepressants) psychotherapy hypnotherapy, biofeedback and relaxation therapy acupuncture and patient information. We also identified new evidence in the following areas that was inconsistent with, or not covered by, current recommendations, but the evidence was not considered to impact on the guideline: ondansetron vitamin D supplementation herbal medicines. We did not find any new evidence on reflexology, psychosocial interventions, or self-help and support groups.
    [Show full text]