Naslov
Thermoanalytical approach to physicochemical compatibility evaluation of 5-aminosalicylates and folic acid

Autori
Jeličić, Mario-Livio ; Brusač, Edvin ; Kurajica, Stanislav ; Amidžić Klarić, Daniela ; Nigović, Biljana ; Mornar, Ana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of abstracts of the 6th Central and Eastern European Conference on Thermal Analysis and Calorimetry (CEEC-TAC6) and 15th Mediterranean Conference on Calorimetry and Thermal Analysis (Medicta2021) / Rotaru, Andrei ; Erceg, Matko - Craiova, 2021, 129-129

ISBN
978-606-11-7861-2

Skup
6th Central and Eastern European Conference on Thermal Analysis and Calorimetry (CEEC-TAC) ; 15th Mediterranean Conference on Calorimetry and Thermal Analysis (MEDICTA)

Mjesto i datum
Split, Hrvatska, 20.07.2021. - 24.07.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
folic acid ; compatibility ; aminosalicylates ; differential scanning calorimetry ; isothermal stress testing

Sažetak
Differential scanning calorimetry (DSC) is the first technique of choice when it comes to compatibility evaluation between components of physical blends in the development of pharmaceuticals. Its main advantage is fast acquisition of information regarding the potential interactions of components in blends which are manifested through changes in characteristic thermograms of blends compared to those of pure compounds. Physicochemical compatibility of folic acid (FA) and two 5-aminosalicylates (5-ASA), balsalazide (BSZ) and olsalazine (OSZ), used in the therapy of inflammatory bowel diseases was investigated using DSC and isothermal stress testing (IST), as a prerequisite to the development of 5-ASA/FA fixed-dose combinations. Thermograms of pure compounds as well as their blends in various ratios (5-ASA : FA 10:1, 5:1, 2:1 and 1:1, m/m) were obtained on a Diamond DSC (Perkin Elmer Inc., Waltham, MA, USA) with a heating rate of 10 °C/min, under the atmosphere of pure nitrogen with the gas flow of 25 mL/min. IST was conducted on pure drug substances and their blends, in a ratio of 10:1, 5:1, 2:1 and 1:1 in favour of both 5-ASAs and FA, by keeping the samples at 50 °C for four weeks. IST was followed by chromatographic analysis of stressed samples using high-performance liquid chromatography. OSZ and FA showed peaks that correspond to their melting, whilst BSZ showed no characteristic melting peak, however, one peak that occurred corresponds to its dehydration since it comes in the form of a dihydrate, which can provide relevant information regarding its physicochemical properties. DSC results implied compatibility between FA and two 5-ASAs (no notable shifts in peak temperatures, < 5°C). Results obtained by chromatographic analysis of samples subjected to IST showed that recoveries of both 5-ASAs and FA in all stressed samples did not markedly differ (97.9 – 103.0%, with the relative standard deviation not exceeding 2.4%). Results obtained by DSC and IST imply that there was no notable change in the physical or chemical nature of 5-ASAs and FA when combined in the same blend. Although DSC measurements can sometimes be misleading due to the exposure of samples to extreme temperatures, it is always recommended to support those results by using other techniques, such as IST.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

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