Naslov
In silico prediction of drug properties and HPLC assay method development for new aminosalicylate/folic acid formulation

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

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

Izvornik
19th International Chromatography School / Ašperger, Danijela ; Ukić, Šime - Zagreb : Fakultet kemijskog inženjerstva i tehnologije Sveučilišta u Zagrebu, 2019, 18-19

ISBN
978-953-6470-88-4

Skup
19th International Chromatography School

Mjesto i datum
Zagreb, Hrvatska, 10.06.2019. - 11.06.2019

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
upalne bolesti crijeva ; HPLC assay ; aminosalicylates ; folic acid
(inflammatory bowel disease ; HPLC sadržaj, sminosalicilati, folna kiselina)

Sažetak
In silico prediction of drug metabolism and fate is a growing approach in drug development. Various studies should be performed as early as possible in the drug development process to get a brief insight into molecule characteristics, such as absorption, distribution, metabolism and excretion (ADME). Methods used to examine molecule characteristics such as lipophilicity, solubility and plasma protein binding require active pharmaceutical ingredient to be synthesized and analyzed and that is, in first place, expensive, but also time consuming. In silico approach offers fast and inexpensive way to obtain information about the specific molecule through many on-line prediction platforms. Inflammatory bowel disease is a chronic inflammatory state that can affect the entire gastrointestinal tract, commonly known as Crohn’s disease, or it can take place mainly in the colon, which is known as Ulcerative colitis. Due to damaged sidewalls of intestine folic acid is malabsorbed, and as consequence, leads to development of megaloblastic anemia. Novel fixed dose combination of one aminosalicylate (mesalazine, sulfasalazine, olsalazine and balsalazide) and folic acid could be used in the treatment of inflammatory bowel disease to simplify the therapy and to make sure that folic acid is compensated, especially in the case of sulfasalazine and olsalazine, which additionally inhibit its absorption. To characterize active pharmaceutical ingredients, lipophilicity and ADME parameters should be investigated and therefore correlated with in silico predicted values to investigate their applicability. Furthermore, to control the quality of proposed fixed dose combination, analytical methods should be developed. Experiments were done on HPLC-DAD system using high throughput methods and various columns from conventional octadecylsilyl column to biomimetic chromatographic columns such as: immobilized artificial membrane (IAM), human serum albumin (HSA) and α-1 acid glycoprotein (AGP). Experimental results were correlated with predicted parameters such as lipophilicity, plasma protein binding and Caco-2 permeability from 14 on-line platforms. Six of them showed good correlation with experimentally obtained values (R from 0.89 to 0.96), implying that in silico prediction has great potential in screening of similar properties in drug discovery. Second part of the research was to develop a single RP-HPLC-DAD method for determination of assay in proposed fixed dose combination of each representative of aminosalicylate group and folic acid. The method was developed on Waters XBridge Phenyl (150×4.6 mm, 3.5 µm) column with gradient elution using 0.2% (v/v) HCOOH in water as mobile phase A and 0.2% (v/v) HCOOH in methanol as mobile phase B. The method was validated according to ICH Q2(R1) guideline where all obtained validation parameters were within the acceptable ranges. Therefore, according to obtained results, it can be confirmed that the method is suitable for future research.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA