Naslov
Transfer of metal impurities during the mechanochemical synthesis of praziquantel cocrystals, polymeric dispersion and cyclodextrin complex

Autori
Jablan, Jasna ; Margui, Eva ; Posavec, Lidija ; Klarić, David ; Cinčić, Dominik ; Galić Nives ; Jug, Mario

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

Izvornik
Genetics and Applications / - , 2023, 67-67

Skup
International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina - ABMBBIH

Mjesto i datum
Sarajevo, Bosna i Hercegovina, 18.05.2023. - 20.05.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
elemental impurities, mechanochemistry, praziquantel

Sažetak
Mechanochemical synthesis by grinding is a versatile, environmentally friendly chemical approach able to address the problems of limited drug solubility and associated low oral bioavailability through the preparation of amorphous drug forms or their cocrystals, polymeric dispersions and cyclodextrin complexes. However, wearing of the grinding apparatus during the mechanochemical synthesis may introduce metal impurities into the products obtained. The presence of metal impurities in pharmaceutical products is of great concern, as may lead to significant toxicity upon administration and/or negatively affect the chemical stability and shelf life of the product by catalysing the degradation of the drug and/or excipients used in the formulation, thus their content must be monitored. In this work, praziquantel (PZQ) was co-ground with malic acid, poloxamer F-127, and hydroxypropyl-β-cyclodextrin to obtain cocrystals, dispersions and inclusion complexes able to improve the low oral bioavailability of the commercially available anhydrous Form A of the drug. Grinding was performed in stainless steel and agate jars with a ball of the same material at different processing times (30 and 90 minutes) to systematically study the transfer of potential impurities from the grinding apparatus to the final products. The metal impurities present in the obtained products were quantified by inductively coupled plasma mass spectrometry. The results obtained show that products obtained in an agate- based setup contain a smaller amount of metallic impurities than those prepared using stainless steel-based apparatus under the same grinding time. It should be noted that only one sample, produced using stainless steel apparatus, showed an increase in the content of elemental impurities (Cr and Fe) due to an increase in the reaction time. For all other samples, the elemental contents are generally similar regardless the grinding time applied and was mostly introduced into the products through the reactants.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA