Physicochemical compatibility determination of 5-aminosalicylates and folic acid as a prerequisite for the development of a fixed-dose combination

Autor: Jeličić, Mario-Livio
Přispěvatelé: Mornar Turk, Ana
Jazyk: chorvatština
Rok vydání: 2021
Předmět:
Popis: Crohnova bolest i ulcerozni kolitis, poznatiji kao upalne bolesti crijeva, predstavljaju kronične upalne bolesti gastrointestinalnog trakta. Zacjeljivanje sluznice i postizanje duboke remisije omogućuje se ciljanom terapijom, međutim postoje skupine pacijenata kojima koristi isključivo liječenje protuupalnim lijekovima iz skupine 5-aminosalicilata; mesalazin i njegovi prolijekovi sulfasalazin, balsalazid i olsalazin. Nedostatak folne kiseline primijećen je u više od polovine oboljelih od Crohnove bolesti i više od trećine pacijenata s ulceroznim kolitisom. Njezin nedostatak može dovesti do razvoja megaloblastične anemije, a povezan je i s povećanom prevalencijom karcinoma debelog crijeva, stoga se uz redovitu terapiju često propisuju povišene doze folne kiseline od 1 do 5 mg na dan. Razvojem fiksnih kombinacija lijekova potencijalni rizik od nepridržavanja propisane terapije nastoji se svesti na najmanju moguću mjeru, što je posebno važno kod pacijenata koji boluju od kroničnih bolesti gdje se terapija sastoji od više lijekova iz različitih farmakoloških skupina. Razvoj fiksnih kombinacija lijekova složen je postupak u kojem važnu ulogu ima ispitivanje fizikalno-kemijskih svojstava svakog pojedinog lijeka kao i njihovih smjesa. U ovom radu predložene su analitičke metode kao podrška razvoju fiksnih kombinacija 5-aminosalicilata i folne kiseline pri čemu su korištene različite analitičke tehnike, poput termalnih, spektroskopskih te kromatografskih, s ciljem ispitivanja fizikalno-kemijske kompatibilnosti 5-aminosalicilata i folne kiseline. Provedena istraživanja pokazala su da su ispitivani 5-aminosalicilati; mesalazin, sulfasalazin, balsalazid i olsalazin, fizikalno-kemijski kompatibilni s folnom kiselinom, što otvara mogućnost za daljnja ispitivanja potrebna za razvoj predloženih fiksnih kombinacija. Crohn's disease and ulcerative colitis, better known as inflammatory bowel diseases, are chronic inflammatory diseases of the gastrointestinal tract. Healing of the mucosa and achieving deep remission is achieved by targeted therapy, however there are groups of patients who benefit exclusively from treatment with anti-inflammatory drugs from the group of 5-aminosalicylates; mesalazine and its prodrugs sulfasalazine, balsalazide and olsalazine. Folic acid deficiency has been observed in more than half of Crohn’s disease patients and more than a third of patients with ulcerative colitis. Its deficiency can lead to the development of megaloblastic anemia, and is associated with an increased prevalence of colorectal cancer, so in regular therapy, increased doses of folic acid of 1 to 5 mg per day are often prescribed. With the development of fixed-dose combinations, the potential risk of non-compliance with prescribed therapy is minimized, which is especially important in patients with chronic diseases where therapy consists of several drugs from different pharmacological groups. The development of fixed drug combinations is a complex process in which an important role is played by the examination of the physicochemical properties of each individual drug as well as their mixtures. In this paper, analytical methods are proposed to support the development of fixed combinations of 5-aminosalicylate and folic acid using various analytical techniques, such as thermal, spectroscopic and chromatographic, to test the physicochemical compatibility of 5-aminosalicylate and folic acid. Studies have shown that 5-aminosalicylates; mesalazine, sulfasalazine, balsalazide and olsalazine, are physicochemically compatible with folic acid, which opens the possibility for further testing required for the development of the proposed fixed combinations.
Databáze: OpenAIRE
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