DOCSLIB.ORG

Development of a Topical Anti- Inflammatory Flurbiprofen Gel

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Development of a Topical Anti- Inflammatory Flurbiprofen Gel UNIVERSIDADE DE LISBOA Faculdade de Farmácia DEVELOPMENT OF A TOPICAL ANTI- INFLAMMATORY FLURBIPROFEN GEL Dissertação elaborada para a obtenção do grau de Mestre em Engenharia Farmacêutica Lisboa 2016 Joana Raquel Baptista de Brito Martins Orientadores: Professora Doutora Helena Margarida Ribeiro e Doutora Sara Raposo UNIVERSIDADE DE LISBOA Faculdade de Farmácia DEVELOPMENT OF A TOPICAL ANTI- INFLAMMATORY FLURBIPROFEN GEL Dissertação elaborada para a obtenção do grau de Mestre em Engenharia Farmacêutica Lisboa 2016 Joana Raquel Baptista de Brito Martins Orientadores: Professora Doutora Helena Margarida Ribeiro e Doutora Sara Raposo i Abstract All over the years, anti-inflammatory therapy is being related to non-steroids anti-inflammatory drugs (NSAIDs). This therapeutic class has proved promising on the market once it decreases systemic adverse effects. In Portugal, there is actually 59 anti-inflammatory drugs for topical use allowed to be commercialized (Autorização de Introdução no Mercado – AIM) by Infarmed under the dosage form of gel. The main aim of this work was a topical non-steroid anti-inflammatory hydrogel development. There is no product with topical application, on the Portuguese market, with flurbiprofen. The patent describing Froben ® manufacturing, commercialized by Abbott, was used as a model. This product describes a formulation with 5% of flurbiprofen. It was developed drug solubility studies, polymer quantity and cutaneous promoters selection. For that, a Quality by Design (QbD) approach was used. The menthol and oleic acid were used as permeation enhancers because they are associated to permeability and dermic retention increase. After that, final formulations were developed, and the skin permeation and retention studied. The results were compared with the oleogel formulation described by the patent. Stability studies described on ICH Q1A (R2) guideline were also performed. Results concluded that hydrogel formulation was well succeeded. The formulation met the percentages of the patent (5% of API, 84.11% of solubilizing system, 2.5% of polymer and the remaining in permeation enhancers and solubilizing). Apart from that, the in vitro studies showed a higher percentage of flurbiprofen on bellow layers of the skin. A higher concentration of drug in this layers is desirable dual to their peripheral effect. Keywords: Non-steroid anti-inflammatory drugs; topical delivery; permeation enhancers; hydrogel formulation; design of experiments; quality by design; flurbiprofen. ii Resumo A terapia anti-inflamatória tem estado, ao longo dos anos, diretamente relacionada com o uso de anti inflamatórios não esteroides (AINEs); contudo, o uso desta classe terapêutica para uso tópico tem vindo a ganhar particular destaque no mercado pois permite a redução de efeitos adversos sistémicos, como por exemplo, reações gastrointestinais. Atualmente em Portugal encontram-se registados 59 medicamentos anti inflamatórios para uso tópico com autorização de introdução no mercado (AIM) pelo Infarmed sob a forma farmacêutica de gel. O presente trabalho visa o desenvolvimento de um hidrogel anti inflamatório não esteroide para uso tópico. Uma vez que não existe qualquer produto de aplicação tópica, no mercado português, com o princípio ativo de flurbiprofeno, esse será o objeto deste estudo, recorrendo a uma patente que descreve o processo de fabrico do produto em questão, tendo como base o Froben ® comercializado pela empresa Abbott. Este produto descreve uma formulação contendo 5% de flurbiprofeno, na qual, são utilizados promotores cutâneos de forma a promover a permeação do fármaco. O primeiro dos objetivos deste projeto consistiu no desenvolvimento galénico da formulação tópica de flurbiprofeno no qual se englobam os estudos de solubilidade do fármaco, seleção da quantidade de polímero e seleção dos promotores cutâneos, este último, recorrendo a uma otimização por Quality by Design (QbD). Após desenvolvidas e caracterizadas, foi também estudada a permeação e retenção do fármaco na pele, comparando os resultados obtidos com a referência deste trabalho; posteriormente, estudos de estabilidade recorrendo à guideline ICH Q1A (R2). Os resultados obtidos permitem concluir que a formulação de um hidrogel foi bem-sucedida, uma vez que, conseguiu-se desenvolver um produto que cumpria com as percentagens descritas pela patente analisada (5% de principio ativo, 80.11% de sistema de dissolução do API, 2.5% de polímero e o restante com promotores cutâneos e solubilizantes). Para além disso, os estudos in vitro de permeação e retenção demonstraram a maior percentagem de retenção do princípio ativo em camadas inferiores onde se pretende que haja maior concentração devido ao seu efeito periférico nas camadas inferiores; o uso de promotores cutâneos como o mentol e o ácido oleico poderão estar associados com o aumento da permeabilidade aumentando assim a retenção dérmica. Palavras-chave: Anti-inflamatórios não esteroides; aplicação tópica; promotores cutâneos; formulação de hidrogel; design of experiments; quality by design, flurbiprofeno. iii Agradecimentos Gostaria de agradecer a todos os intervenientes à elaboração desta dissertação que contribuíram de alguma maneira para a possibilidade da sua realização: À professora Doutora Helena Margarida Ribeiro pela disponibilidade em me acolher neste projeto, pela simpatia e amabilidade para me ajudar sempre que solicitada; À Doutora Sara Raposo por toda a ajuda e paciência para a elaboração deste projeto, bem como todas as palavras de incentivo nos momentos de desânimo; À Doutorada Joana Marto por toda a ajuda na realização desta dissertação desde a parte laboratorial até à parte teórica, bem como toda a paciência, disponibilidade, boa disposição e preocupação constantes; Aos professores Doutor António Almeida e Doutor José Menezes como coordenadores do mestrado, bem como os restantes professores que integram o mestrado de Engenharia Farmacêutica pela disponibilidade constante ao longo destes dois anos; Ao Laboratório Edol, Produtos Farmacêuticos S.A. por toda a disponibilização de todos os recursos necessários à elaboração deste trabalho bem como a todos colaboradores da empresa, com um especial agradecimento aos colaboradores do departamento de Controlo de Qualidade, que sempre prontamente se mostraram disponíveis para qualquer dúvida, e sem ordem em particular: Fátima Morais, Raquel Ferreira, Teresa Fernandes, Daniel Arranca, Carmo Rosa, Joana Vidinha, Mónica Salvaterra, Marco Rodrigues, Alexandra Marques, Carla Pires, Paula Carvalho e Sofia Bravo; À Ana Marta, Bárbara e Joana: obrigada por todos os momentos de incentivo, força e boa disposição que me ajudaram a ultrapassar os momentos mais difíceis; à Marina: obrigada por me acompanhares nesta caminhada desde sempre e por toda a grande amizade; a todos os meus amigos; Aos meus pais, por todo o apoio que sempre me deram, tanto para a realização de todo o meu percurso académico, bem como em todos os momentos da minha vida. A eles, lhes devo tudo, e por isso, o meu maior obrigado. A toda a minha família, por serem quem são, por estarem lá sempre que precisei e por viverem a minha vida académica desde que a iniciei; Ao João, por estar comigo em todos os momentos. iv Table of Contents Abstract ................................................................................................................................. i Resumo ................................................................................................................................ iii Agradecimentos .................................................................................................................. iv List of Figures ...................................................................................................................... viii List of Tables ........................................................................................................................ x Abbreviations & Symbols .................................................................................................. xii 1st Chapter - Introduction .................................................................................................... 1 1. Introduction .................................................................................................................. 1 1.1. Rheumatoid Arthritis ......................................................................................................... 1 1.1.1. Epidemiology ............................................................................................................... 1 1.1.2. Pathogenesis ............................................................................................................... 1 1.1.3. Diagnosis ...................................................................................................................... 3 1.1.4. Treatment ...................................................................................................................... 4 1.1.4.1. Disease-modifying anti-rheumatoid drugs (DMARDs) ............................. 4 1.1.4.2. Corticosteroids.................................................................................................... 5 1.1.4.3. Non steroid anti-inflammatory drug (NSAIDs) ............................................ 5 1.1.4.3.1. NSAIDs in national market .......................................................................... 7 1.2. Dermal application systems ...........................................................................................
Load more

Recommended publications
  • Etofenamate and Anastomoses of the Colon in Rats
    Turk J Med Sci ORIGINAL ARTICLE 2009; 39 (5): 713-718 © TÜBİTAK E-mail: [email protected] doi:10.3906/sag-0901-32 Aydın İNAN Etofenamate and anastomoses of the colon in rats Önder SÜRGİT Meral ŞEN Aim: Non-steroidal anti-inflammatory drugs have been used for many years due to their analgesic and anti-inflammatory properties. They have also been used for postoperative analgesia. We aimed Ayhan AKPINAR to study the effects of etofenamate, a non-steroidal anti-inflammatory drug, on the healing of colonic Mikdat BOZER anastomoses in rats. Materials and methods: Sprague-Dawley rats were used in this study. Resection and anastomosis were performed on the distal colon. The etofenamate group received 30 mg/kg etofenamate and the control group received 0.1 mL of 0.9% NaCl intramuscularly daily. Bursting pressures of anastomoses and hydroxyproline levels of perianastomotic tissues were determined on days 3 and 7. Results: Four deaths were observed in each group. Mean bursting pressures (etofenamate group, day 3: 50.50 ± 7.27 mmHg, day 7: 187.37 ± 12.20 mmHg; control group, day 3: 55.13 ± 5.94 mmHg, day 7: 202.12 ± 18.64 mmHg) and mean hydroxyproline levels (etofenamate group, day 3: 2.18 ± 0.17 Department of General Surgery, μg/mg tissue, day 7: 4.34 ± 0.79 μg/mg tissue; control group, day 3: 2.20 ± 0.12 μg/mg tissue, day 7: Faculty of Medicine, 5.07 ± 0.65 μg/mg tissue) in the etofenamate group were lower than those in the control group on Fatih University, both days 3 and 7.
    [Show full text]
  • Allergic and Photoallergic Contact Dermatitis to Topical Non-Steroidal Anti-Inflammatory Drugs: a Case Series from Turkey
    CONTACT DERMATITIS AND OCCUPATIONAL DERMATOSES ALLERGIC AND PHOTOALLERGIC CONTACT DERMATITIS TO TOPICAL NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: A CASE SERIES FROM TURKEY E Ozkaya (1) - A Kutlay (1) Istanbul University Istanbul Medical Faculty, Dermatology, Istanbul, Turkey (1) Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are widely used, mainly for soft tissue pain and injury. Allergic contact dermatitis (ACD) and photoallergic contact dermatitis (PACD) from topical NSAIDs have been reported with an increasing incidence. Ketoprofen seems to be the major culprit drug, followed by etofenamate and bufexamac in many European countries. There are only limited data on this subject in Turkey. Observation: Out of 2375 consecutively patch tested patients in our clinic between 1996 and 2017, 13 patients (7 male, 6 female, age range: 21-81, median: 56 years) (0.5%) were diagnosed with topical NSAID-induced ACD/PACD. Patients were patch tested (n=13) and photopatch tested (n=4) with the suspected topical preparations as is, and with the active (n=4) and inactive ingredients, when available, in addition to the European baseline series. Etofenamate (tested in a dilution series of 1%-5%-10% in petrolatum and aqua) was the leading culprit drug in 8 patients (62%), followed by ketoprofen (n=2), diclofenac (n=2), and diethylamine salicylate & naproxen (n=1). The main diagnosis was ACD whereas PACD was diagnosed in 2 patients from etofenamate and ketoprofen. Concomitant positive reaction were observed with inactive ingredients such as benzyl alcohol in etofenamate, and neroli oil in ketoprofen preparations, respectively. Cross-reaction to fragrances (fragrance mix I, balsam of Peru, cinnamic alcohol/aldehyde) was present in both patients with ketoprofen allergy.
    [Show full text]
  • Preemptive Use of Etofenamate in Laparoscopic Cholecystectomy: a Randomized, Placebo-Controlled, Double-Blind Study
    Original Article Preemptive Use of Etofenamate in Laparoscopic Cholecystectomy: A Randomized, Placebo-Controlled, Double-Blind Study. Meral Şen1, Aydın İnan1, Hüseyin Sert2, Ayhan Akpınar1, Cenap Dener1 Fatih University, Medical School, ABSTRACT Departments of General Surgery1 and Anesthesiology2, Ankara, Turkey Aim: To investigate the preemptive effect of etofenomate on postoperative pain and emesis in the first 24 hours after elective Eur J Gen Med 2010;7(1): 50-55 laparoscopic cholecystectomy. Method: Patients were randomly assigned to two groups each consisting of 60 patients. Group A was received 1g (2 ml) etofenomate intramuscularly, group B was received 0.9% saline intramuscularly one hour before surgery. All patients were administered meperidine HCl in the patient –controlled analgesia (PCA) intravenous mode in order to treat postoperative pain. Pain intensity was assessed on visual analog scales (VAS) at four times; 1 hour, 6 hours, 12 hours and 24 hours. The total meperidine HCl consumptions, VAS scores and antiemetic requirements were recorded and comparisons among the two groups were evaluated. Result: The mean total meperidine HCl consumptions within first 6 and 24 hours of the group A were significantly less than the group B. The VAS scores at 1 and 6 hours in the group A were significantly lower than that in the group B. There was no significant difference in the postoperative antiemetic requirement among two groups. Conclusion: Preemptive use of etofenamate reduces pain intensity and meperidine HCl requirement, but it doesn’t
    [Show full text]
  • Innovations from 'Down-Under': a Focus on Prescription to Non-Prescription Medicine Reclassification in New Zealand and Australia
    ORIGINAL ARTICLE SelfCare 2012;3(5):88-107 Advancing the study&understanding of self-care INNOVATIONS FROM ‘DOWN-UNDER’: A FOCUS ON PRESCRIPTION TO NON-PRESCRIPTION MEDICINE RECLASSIFICATION IN NEW ZEALAND AND AUSTRALIA NATALIE GAULD*, FIONA KELLY**, LYNNE EMMERTON†, LINDA BRYANT††, STEPHEN BUETOW‡ * PhD Candidate, Department of General Practice and Primary Health Care, University of Auckland, New Zealand **Honorary Senior Lecturer, School of Pharmacy, University of Auckland, New Zealand †Associate Professor, School of Pharmacy, Curtin Health Innovation Research Institute, Perth, Western Australia †† Honorary Lecturer, Department of General Practice and Primary Health Care, University of Auckland, New Zealand ‡Associate Professor, Department of General Practice and Primary Health Care, University of Auckland, New Zealand ABSTRACT BACKGROUND: Australia and New Zealand (NZ) contribute to the international trend of medicines reclassification from prescription to non-prescription availability (switch). Both countries have been acknowledged as being as advanced or even more so than the United Kingdom (UK) in availability of medicines without prescription, despite not making some of the recent innovative UK switches. OBJECTIVE: To derive a measure of progressiveness in switch; to compare the progressiveness of switch between NZ and Australia; and to compare NZ and Australia switch activity with the UK. METHODS: Records of medicines classification meetings in Australia and NZ from 2000 to 2011 were analysed with respect to all switch considerations (whether approved or not approved). Switches in Australia and NZ were compared with those in the UK. A new measure, ‘innovative switches’, was developed to provide a useful measure of switch progress. RESULTS: Australia demonstrated ‘switch innovation’ in the early 2000s, including the ‘first-in-world’ switch of orlistat, but has slowed down since.
    [Show full text]
  • Nsaids: Friend Or Foe in the Battle Against Pain?
    NSAIDs: Friend or Foe in the Battle against Pain? Presented by June E. Oliver, MSN, CCNS, AP-PMN, APRN/CNS NO Conflicts of Interest to Declare Old & Natural! 1763 fever Rx- bark/leaves of willow/myrtle (salicylic acid) 1859-chemical structure discovered & synthesized in Germany 1914- Bayer Co. started manufacturing ASA Current sales 11 billion ( 2014) Early 20 th Century- NSAIDs discovered 1971- discovered mechanism of action of NSAIDs by John R. Vane 1990s-COX-2 isoenzyme successfully identified & cloned Current- script & OTC use = > 30 billion doses/yr of NSAIDs In US Numbers increase every year Prostaglandin (PG) Mechanism of Action Prostaglandins( PG) - lipids derived from acids: i.e. arachidonic (AA), lineolic, others PGs have Variety of functions Constitutive GI mucosal protection Kidney function Trauma response Cell membrane trauma- releases AA & COX enzyme converts to PGs inflammation Peripheral & central sensitization of nociceptors to mechanical & chemical stimuli Pyretic response PGs rise in CSF w/ pyrogen introduction Although not an NSAID, acetaminophen blocks brain PG synthetase (COX3 inhibition ) Cyclo-oxygenase (COX): “The Convertors” Cyclo-oxygenase 1&2 = isoenzymes that convert AA to PGs (i.e. prostacyclin, & thromboxanes) COX-1 Expressed regularly- provides gastric & duodenal mucosal protection Stimulates production mucin/bicarbonate/phospholipid that covers surface of stomach Enhances GI mucosal blood flow w/ local vasodilation Enhanced epithelial cell reproduction & migration towards lumen Can be induced
    [Show full text]
  • 1 Adverse Reaction of Topical Etofenamate
    Adverse Reaction of Topical Etofenamate: Petechial Eruption Z Orbak1, ZK Yildirim2, O Sepetci3 , C Karakelleoglu3, H Alp3 ABSTRACT Etofenamate is a non-steroidal anti-inflammatory drug (NSAID). Clinical findings caused by etofenamate are uncommon. Allergic contact dermatitis is the most common cutaneous reaction reported. But petechial eruption due to etofenamate had not been reported yet. This report concerns an 11-year old male with petechial eruption after application of topical etofenamate. Physicians need to be aware that patients can develop an asymptomatic purpuric eruption when etofenamate is ordered. Keywords: Adverse reaction, etofenamate, petechial eruption ___________________________________________________________________________ From: 1Department of Paediatric Endocrinology and Metabolism, 2Department of Paediatric Haematology and Oncology and 3Department of General Paediatrics, Atatürk University, Faculty of Medicine, Erzurum, Turkey. Correspondence: Dr Z Orbak, Department of Paediatrics, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey. E-mail: [email protected] 1 INTRODUCTION Etofenamate is a non-steroidal anti-inflammatory drug (NSAID). It has analgesic, antirheumatic, antipyretic and anti-inflammatory properties. It is a non-selective COX (cyclo-oxygenase) inhibitor. Cyclo-oxygenase is an enzyme and is responsible for production of numerous chemicals, including prostaglandins in the body. Etofenamate inhibits prostaglandin synthesis, and provides analgesic and anti-inflammatory effects. After etofenamate, formulated in gel, is applied directly to inflamed tissue, it quickly penetrates through the corneal layer of the skin area of application and reaches therapeutically effective concentrations in the subcutis, fascias, ligaments and muscles. However, there are less systemic side effects of topical etofenamate (1, 2). Clinical adverse findings caused by etofenamate are uncommon. There have been infrequent reports on the incidence of side effects of etofenamate.
    [Show full text]
  • Optimization and Evaluation of the in Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs
    pharmaceutics Article Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M® Membrane Bartłomiej Milanowski 1,2,* , Hanna Wosicka-Fr ˛ackowiak 1,2, Eliza Główka 1,2,† , Małgorzata Sosnowska 2, Stanisław Wo´zny 2, Filip Stachowiak 2, Angelika Suchenek 3 and Dariusz Wilkowski 3 1 Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780 Pozna´n,Poland; [email protected] 2 GENERICA Pharmaceutical Lab, Regionalne Centrum Zdrowia Sp. z o. o., ul. Na K˛epie3, 64-360 Zb ˛aszy´n,Poland; [email protected] (M.S.); [email protected] (S.W.); [email protected] (F.S.) 3 MYLAN Healthcare Sp. z o. o., ul. Post˛epu21B, 02-676 Warszawa, Poland; [email protected] (A.S.); [email protected] (D.W.) * Correspondence: [email protected] or [email protected]; Tel.: +48-061-854-66-59 † Dr. Główka passed away on 17 December 2020. Abstract: Pharmaceutical products containing non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed topical formulations used for analgesic and antirheumatic properties. Citation: Milanowski, B.; These drugs must overcome the skin barrier to cause a therapeutic effect. Human skin has been widely Wosicka-Fr ˛ackowiak, H.; Główka, E.; used as a model to study in vitro drug diffusion and permeation, however, it suffers from many Sosnowska, M.; Wo´zny, S.; Stachowiak, limitations. Therefore, to perform in vitro permeation test (IVPT), we used a Strat-M® membrane F.; Suchenek, A.; Wilkowski, D.
    [Show full text]
  • Topical Nsaids for Chronic Musculoskeletal Pain in Adults (Review)
    Cochrane Database of Systematic Reviews Topical NSAIDs for chronic musculoskeletal pain in adults (Review) Derry S, Conaghan P, Da Silva JAP, Wiffen PJ, Moore RA Derry S, Conaghan P, Da Silva JAP, Wiffen PJ, Moore RA. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No.: CD007400. DOI: 10.1002/14651858.CD007400.pub3. www.cochranelibrary.com Topical NSAIDs for chronic musculoskeletal pain in adults (Review) Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 6 OBJECTIVES ..................................... 7 METHODS ...................................... 7 RESULTS....................................... 10 Figure1. ..................................... 11 Figure2. ..................................... 14 Figure3. ..................................... 16 Figure4. ..................................... 17 Figure5. ..................................... 20 DISCUSSION ..................................... 22 Figure6. ..................................... 23 AUTHORS’CONCLUSIONS . 24 ACKNOWLEDGEMENTS . 25 REFERENCES ..................................... 26 CHARACTERISTICSOFSTUDIES . 31 DATAANDANALYSES. 73 Analysis 1.1. Comparison 1 Topical diclofenac versus carrier, Outcome 1 Clinical success. 74 Analysis
    [Show full text]
  • Plants As Sources of Anti-Inflammatory Agents
    molecules Review Plants as Sources of Anti-Inflammatory Agents Clara dos Reis Nunes 1 , Mariana Barreto Arantes 1, Silvia Menezes de Faria Pereira 1, Larissa Leandro da Cruz 1, Michel de Souza Passos 2, Luana Pereira de Moraes 1, Ivo José Curcino Vieira 2 and Daniela Barros de Oliveira 1,* 1 Laboratório de Tecnologia de Alimentos, Centro de Ciências e Tecnologias Agropecuárias, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil; [email protected] (C.d.R.N.); [email protected] (M.B.A.); [email protected] (S.M.d.F.P.); [email protected] (L.L.d.C.); [email protected] (L.P.d.M.) 2 Laboratório de Ciências Químicas, Centro de Ciências e Tecnologia, UniversidadeEstadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ 28013-602, Brazil; [email protected] (M.d.S.P.); [email protected] (I.J.C.V.) * Correspondence: [email protected]; Tel.: +55-22-988395160 Academic Editors: Thea Magrone, Rodrigo Valenzuela and Karel Šmejkal Received: 29 June 2020; Accepted: 5 August 2020; Published: 15 August 2020 Abstract: Plants represent the main source of molecules for the development of new drugs, which intensifies the interest of transnational industries in searching for substances obtained from plant sources, especially since the vast majority of species have not yet been studied chemically or biologically, particularly concerning anti-inflammatory action. Anti-inflammatory drugs can interfere in the pathophysiological process of inflammation, to minimize tissue damage and provide greater comfort to the patient. Therefore, it is important to note that due to the existence of a large number of species available for research, the successful development of new naturally occurring anti-inflammatory drugs depends mainly on a multidisciplinary effort to find new molecules.
    [Show full text]
  • Intramuscular Etofenamate Versus Diclofenac in the Relief of Renal Colic a Randomised, Single-Blind, Comparative Study
    Clin Drug Invest 2003; 23 (11): 701-706 ORIGINAL RESEARCH ARTICLE 1173-2563/03/0011-0701/$30.00/0 © Adis Data Information BV 2003. All rights reserved. Intramuscular Etofenamate versus Diclofenac in the Relief of Renal Colic A Randomised, Single-Blind, Comparative Study Avelino Fraga,1 Martinho de Almeida,2 V´itor Moreira-da-Silva,2 Manuel Sousa- Marques,3 Lu´is Severo,3 Alberto Matos-Ferreira,4 Lu´is Campos-Pinheiro,4 Mario´ Reis,5 Ulisses Ribau,5 Pedro Silveira6 and Lu´is Almeida6 1 Hospital D. Pedro V, Porto, Portugal 2 Hospital Pedro Hispano, Matosinhos, Portugal 3 Hospital do Desterro, Lisbon, Portugal 4 Instituto de Urologia, Lisbon, Portugal 5 Hospital S. Joao,˜ Porto, Portugal 6 R&D Department, Laboratorios Bial, S. Mamede do Coronado, Portugal Abstract Objective: To compare the efficacy and adverse effects of intramuscular etofena- mate and intramuscular diclofenac in the relief of acute renal colic. Patients and methods: A multicentre, randomised, single-blind study was per- formed in 119 patients admitted to the emergency room for renal colic. Patients were assigned to treatment with either etofenamate 1000mg or diclofenac 75mg, both administered intramuscularly. Pain was self-assessed using a 4-point verbal rating scale (VRS) and a visual analogue scale (VAS) just before drug administra- tion and 30, 60, 120 and 240 min later. Results: The two groups were similar with regard to baseline characteristics. The percentages of patients who reported an improvement in the VRS at 60 min post-administration (primary variable) were 84.5% with etofenamate and 83.3% with diclofenac (p = 0.73).
    [Show full text]
  • Analgesic Effect of Hldome~¢In, Eto|Enamate and of Ibupro|En Applied Locally in Animals and Man
    by didofenac 100 ~g with a mean value of 16,1 + 1,7 mm Hg (58~o; response inhibited versus control) and the tachycardia was inhibited with a mean value of 39,4 + 0,4 bpm (70~; response versus control). This response was reversed by naloxone pretreatment. Mieroinjections of diclofenac (1 ng-l,0 pg/0,5 pl) in the periaqueductal gray matter (PA(3), hypothalamus and in the preoptic area in rats dose-dependently inhibited the number of writhings. The antinociceptive effect of the dn~£ was inhibited by naloxone, 1 mg/kg, injected s.c. 5 minutes prior to the local injection or 30 minutes after the experiment in a dosage of 50/~g/'0,5/~1 locally. Conclusion: Diclofenac exerts a central, naloxone-reversible antinociceptive action in experimental animals after noxious visceral stimuli but not after somatosensory stimuli. This action is exerted from several different areas within the central nervous system, intimately involved in pein control. i P.w¢.327 ] Analgesic effect of hldome~¢in, eto|enamate and of ibupro|en applied locally in animals and man Jezdinsk~/ *, J., Ondra * *, P., Bret~najdrovfi * * *, M. and Zfiboj * * *, Z. • Dept. of PhatmacologF, * * Dept. of Met£ Chemistry, Medical Faculty of Palacl~ University, Allenda 3, Olomouc and * * * Dept. of Geriatrics, University Hospital, Olomouc, Czechoslovakia Analgesic efficacy of indometacin and of ibuprofen in the form of gel was evaluated in rats with the yeast-induced inflammation of one hind paw by two methods: a) by objective measuring of the duration of the paw-lifting behavior time (H~lek and Jezdinsk~, 1977; Jezdinsk~, 1982) as a manifestation of spontaneous nociceptive reaction; b) by &~,sing the degree of inflammatory hyperalgesia according to Randall-Selitto's method.
    [Show full text]
  • Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation
    pharmaceutics Article Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation Giuliana Mancini 1,2,Lídia M. D. Gonçalves 1 , Joana Marto 1 , Filomena A. Carvalho 3, Sandra Simões 1,*, Helena Margarida Ribeiro 1,* and António J. Almeida 1,* 1 Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal; [email protected] (G.M.); [email protected] (L.M.D.G.); [email protected] (J.M.) 2 LEF, Laboratórios de Estudos Farmacêuticos, 2730-269 Barcarena, Portugal 3 Faculdade de Medicina, Instituto de Medicina Molecular ‘João Lobo Antunes’, Universidade de Lisboa, 1649-003 Lisbon, Portugal; fi[email protected] * Correspondence: [email protected] (S.S.); [email protected] (H.M.R.); [email protected] (A.J.A.) Abstract: Innovative formulations, including solid lipid nanoparticles (SLNs), have been sought to improve skin permeation of non-steroidal anti-inflammatory drugs (NSAIDs). The present study explores the use of SLNs, prepared using a fusion-emulsification method, to increase skin permeation and in vivo activity of two relevant NSAIDs: A liquid molecule (etofenamate) and a solid one (ibuprofen), formulated in a 2% hydroxypropyl methylcellulose gel through the gelation of SLN ® ® suspensions. Compritol 888 ATO and Tween 80 were used as a solid lipid and a surfactant, respectively. All production steps were up scalable, resulting in SLNs with high encapsulation Citation: Mancini, G.; Gonçalves, efficiency (>90%), a mean particle size of <250 nm, a polydispersity index <0.2, and that were L.M.D.; Marto, J.; Carvalho, F.A.; stable for 12 months.
    [Show full text]