Primjena ciklodekstrina u poboljšanju in vitro brzine otapanja flufenaminske kiseline

master's thesis

• Title (english): Application of cyclodextrins to enhance in vitro dissolution rate of flufenamic acid
• Author: Anamaria Maričić
• Mentor: Mario Jug (mentor)
• Committee member: Mario Jug (predsjednik povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Committee member: Jasna Jablan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2021-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Fenamati su zanimljiva skupina nesteroidnih protuupalnih lijekova s obzirom da djeluju kao modulatori širokog spektra ionskih kanala i enzima. Zbog toga potencijalno predstavljaju zanimljive analgetike s drugačijim mehanizmom djelovanja. Unutar ove skupine, ističe se flufenaminska kiselina, koja se ubraja u II. skupinu lijekova prema BCS klasifikaciji, s obzirom da je niske topljivosti i visoke permeabilnosti. Zbog niske topljivosti u vodi je njena oralna bioraspoloživost niska što posljedično ograničava kliničku primjenu ovog lijeka. Na tržištu Europske unije dostupna je samo u Italiji kao topikalni pripravak za primjenu na kožu. Cilj ovoga rada je poboljšanje biofarmaceutskih karakteristika flufenaminske kiseline primjenom različitih ciklodekstrin. Istraživanje obuhvaća prirodni β-ciklodekstrin (β-CD) te njegove hidrofilne derivate hidroksipropil-β-ciklodekstrin (HP-β-C ), nasumično metilirani β-ciklodekstrin (RAMEB) te sulfobutileter-β-ciklodekstrin (SBE-β-CD). Binarni sustavi flufenaminske kiseline s ispitivanim ciklodekstinima pripremljeni su primjenom različitih tehnologija kojima je praćena brzina otapanja u in vitro uvjetima. Uzorci pripremljeni mljevenjem lijeka s HP-β-C te koevaporacijom s RAME pokazuju najviše potencijala u prevladavanja biofarmaceutski nepovoljnih karakteristika flufenaminske kiseline, u prvom redu ograničenog in vitro oslobađanja, koji ograničavaju širu terapijsku uporabu flufenaminske kiseline.

Abstract (english)

Fenamates are an interesting group of nonsteroidal anti-inflammatory drugs acting as modulators of a wide range of ion channels and enzymes. Therefore, they potentially represent interesting analgesics with a different mechanism of action. Within this group of drugs, flufenamic acid stands out, which belongs to the II. group of drugs according to the BCS classification, given its low solubility and high permeability. Due to its low aqueous solubility, its oral bioavailability is low and variable, which consequently limits the clinical use of this drug. It is only available on the European Union market in Italy as a topical preparation for application to the skin. This work aims to improve the biopharmaceutical properties of flufenamic acid by applying various cyclodextrins. The study includes natural β-cyclodextrin (β-CD) and its hydrophilic derivatives hydroxypropyl-β-cyclodextrin (HP-β-C ), randomly methylated β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD). Binary systems of flufenamic acid with tested cyclodextrins were prepared using various technologies that monitor the dissolution rate in vitro. Samples prepared by milling the drug with HP-β-CD and co-evaporating with RAMEB show the greatest potential in overcoming the biopharmaceutical unfavorable characteristics of flufenamic acid, primarily limited in vitro dissolution rate, which restricts the wider therapeutic use of that drug.

• Keywords: flufenaminska kiselina; ciklodekstrini; mljevenje; gnječenje; koevaporacija; brzina otapanja
• Keywords (english): flufenamic acid; cyclodextrins; grinding; kneading; co-evaporation; dissolution rate
• Language: croatian
• URN:NBN: urn:nbn:hr:163:459876
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-09-28
• Created on: 2022-02-28 11:39:11