{"?xml":{"@version":"1.0"},"edm:RDF":{"@xmlns:dc":"http://purl.org/dc/elements/1.1/","@xmlns:edm":"http://www.europeana.eu/schemas/edm/","@xmlns:wgs84_pos":"http://www.w3.org/2003/01/geo/wgs84_pos","@xmlns:foaf":"http://xmlns.com/foaf/0.1/","@xmlns:rdaGr2":"http://rdvocab.info/ElementsGr2","@xmlns:oai":"http://www.openarchives.org/OAI/2.0/","@xmlns:owl":"http://www.w3.org/2002/07/owl#","@xmlns:rdf":"http://www.w3.org/1999/02/22-rdf-syntax-ns#","@xmlns:ore":"http://www.openarchives.org/ore/terms/","@xmlns:skos":"http://www.w3.org/2004/02/skos/core#","@xmlns:dcterms":"http://purl.org/dc/terms/","edm:WebResource":[{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-2ESXRE2H/1a304f3f-7dc3-4b25-969d-0705479099cf/HTML","dcterms:extent":"38 KB"},{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-2ESXRE2H/69b9795b-6657-4733-bfc6-bd3f11feaae5/PDF","dcterms:extent":"511 KB"},{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-2ESXRE2H/43b17032-b3f0-4828-94b6-773fbea88668/TEXT","dcterms:extent":"34 KB"}],"edm:TimeSpan":{"@rdf:about":"1998-2025","edm:begin":{"@xml:lang":"en","#text":"1998"},"edm:end":{"@xml:lang":"en","#text":"2025"}},"edm:ProvidedCHO":{"@rdf:about":"URN:NBN:SI:doc-2ESXRE2H","dcterms:isPartOf":[{"@rdf:resource":"https://www.dlib.si/details/URN:NBN:SI:spr-KC6O72BG"},{"@xml:lang":"sl","#text":"Acta chimica slovenica"}],"dcterms:issued":"2010","dc:creator":["Benkič, Primož","Kristl, Albin","Plevnik, Miha","Ritlop, Gregor","Simonič, Igor","Smrkolj, Matej","Vrečer, Franc","Zupančič, Vinko"],"dc:format":[{"@xml:lang":"sl","#text":"številka:2"},{"@xml:lang":"sl","#text":"letnik:57"},{"@xml:lang":"sl","#text":"str. 376-385"}],"dc:identifier":["ISSN:1318-0207","COBISSID:2822769","URN:URN:NBN:SI:doc-2ESXRE2H"],"dc:language":"en","dc:publisher":[{"@xml:lang":"sl","#text":"Slovenian Chemical Society"},{"@xml:lang":"sl","#text":"Slovensko kemijsko društvo"}],"dc:subject":[{"@xml:lang":"sl","#text":"analizna kemija"},{"@xml:lang":"sl","#text":"karakterizacija"},{"@xml:lang":"sl","#text":"klopidogrel"},{"@xml:lang":"sl","#text":"organske snovi"},{"@xml:lang":"sl","#text":"topnost"}],"dcterms:temporal":{"@rdf:resource":"1998-2025"},"dc:title":{"@xml:lang":"sl","#text":"Preformulation investigation of some clopidogrel addition salts|"},"dc:description":[{"@xml:lang":"sl","#text":"Physico-chemical properties of active substances such as solubility, dissolution rate, chemical stability, pharmaceutical processibility, etc. can be improved by salt formation of active substances. Characterization of physical properties of such salts is important for selection of an optimal salt having required biopharmaceutical properties, stability and manufacturability. The present study deals with the preformulation study of selected clopidogrel acid addition salts, i.e. hydrogen sulfate, hydrochloride(HCl), hydrobromide (HBr), besylate and (-)-camphor-10-sulfonate salt (CSA) and two commercially available polymorphic forms of hydrogen sulphate salt, i.e. form 1 (HS F1) and form 2 (HS F2). Clopidogrel salts were characterized by means of thermal analysis (TG, DSC), X-ray powder diffraction(XRPD), infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic vapor sorption (DVS), true density, scanning electron microscopy (SEM) and solubility. Distinct differences in tested parameters were found among acid addition salts and crystalline forms of clopidogrel. Higher melting point of both hydrogen sulphate salt was attributed to presenceof hydrogen bonds among HS anions, connecting them into a chain. All salts included in the present study were anhydrous, except HBr which was in the form of monohydrate. The two tested polymorphic forms of clopidogrel HS salt are enantiotropically related to each other and showed the highest hygroscopicity among the tested salts. This is important for development of solid dosage form containing both polymorphic forms and for selection of primary packaging. Solubility studies in different aqueous media showed comparable solubility for clopidogrel hydrogen sulfate (polymorphic forms 1 and 2), hydrochloride (form 1) and hydrobromide hydrate (form 1) whereas clopidogrel camphorsulfonate (CSA) and besylate salt showed slightly lower solubility"},{"@xml:lang":"sl","#text":"Fizikalno-kemijske lastnosti zdravilnih učinkovin, kot so topnost, hitrost (profil) raztapljanja, kemijska stabilnost, farmacevtsko- tehnološka procesibilnost itd., lahko izboljšamo s tvorbo različnih soli. Karakterizacija fizikalnih lastnosti tovrstnih soli je pomembna za izbiro optimalne soli, ki ima ustrezne biofarmacevtske lastnosti, ustrezno stabilnost in procesibilnost v industrijskem merilu. V nadaljevanju v prispevku predstavljamo predformulacijske študije nekaterih soli klopidogrela z nekaterimi organskimi in anorganskimi kislinami, tj. klorid (HCl), bromid (HBr), besilat, (-)-kafra- 10-sulfonat(CSA) ter hidrogen sulfat, pri slednji smo karakterizirali dve komercialno dostopni polimorfni obliki I (HS F1) in II(HS F2). Soli klopidogrela smo okarakterizirali z uporabo termične analize (TG, DSC), praškovne rentgenske difrakcije (XRPD), infrardeče spektroskopije (FTIR), jedrske magnetne resonance (NMR), dinamične sorpcije par (DVS), prave gostote, elektronske mikroskopije (SEM) in topnosti. Ugotovljene so bile nekatere bistvene razlike v testiranih parametrih med različnimi solmi in kristaliničnimi oblikami klopidogrela. Višje tališče, ugotovljeno za obe polimorfni obliki klopidogrelijeve HS soli, je posledica prisotnih vodikovih vezi med hidrogen sulfatnimi anioni, ki slednje povezujejo v verigo. Klopidogrelijev bromid, uporabljen v naši študiji, je bil v obliki monohidrata, vse preostale preiskovane soli pa so bile anhidrične. Preiskovanikristalni obliki soli klopidogrelijevega hidrogen sulfata HS F1 in HS F2 sta enantiotropni in kažeta najvišjo higroskopnost med vsemi preiskovanimi solmi. To je zlasti potrebno upoštevati pri razvoju trdnih farmacevtskih oblik, ki vsebujejo hidrogensulfatno sol in pri izbiri ustrezne kakovosti in tipa ovojnine. Pri preučevanju topnosti soli klopidogrela v različnih vodnih medijih smo ugotovili primerljivo topnost za soli z anorganskimi kilsinami (hidrogensulfat, klorid in bromid), medtem ko smo za obe soli z organskima kislinama, tj. klopidogrel CSA ter klopidogrel besilat določili nekoliko nižjo topnost"}],"edm:type":"TEXT","dc:type":[{"@xml:lang":"sl","#text":"znanstveno časopisje"},{"@xml:lang":"en","#text":"journals"},{"@rdf:resource":"http://www.wikidata.org/entity/Q361785"}]},"ore:Aggregation":{"@rdf:about":"http://www.dlib.si/?URN=URN:NBN:SI:doc-2ESXRE2H","edm:aggregatedCHO":{"@rdf:resource":"URN:NBN:SI:doc-2ESXRE2H"},"edm:isShownBy":{"@rdf:resource":"http://www.dlib.si/stream/URN:NBN:SI:doc-2ESXRE2H/69b9795b-6657-4733-bfc6-bd3f11feaae5/PDF"},"edm:rights":{"@rdf:resource":"http://creativecommons.org/licenses/by/4.0/"},"edm:provider":"Slovenian National E-content Aggregator","edm:intermediateProvider":{"@xml:lang":"en","#text":"National and University Library of Slovenia"},"edm:dataProvider":{"@xml:lang":"sl","#text":"Slovensko kemijsko društvo"},"edm:object":{"@rdf:resource":"http://www.dlib.si/streamdb/URN:NBN:SI:doc-2ESXRE2H/maxi/edm"},"edm:isShownAt":{"@rdf:resource":"http://www.dlib.si/details/URN:NBN:SI:doc-2ESXRE2H"}}}}