engleski

A chromatographic approach to development of 5‑aminosalicylate/folic acid fxed‑dose combinations for treatment of Crohn’s disease and ulcerative colitis

Medication adherence is an important factor in infammatory bowel disease therapy, which includes regular supplementation of malabsorbed vitamins. Absorption of folic acid is limited due to the damaging of the gastrointestinal tract, which can increase the chances to develop megaloblastic anaemia and colorectal cancer. In this work, 5- aminosalicylates (mesalazine, balsalazide, sulfasalazine and olsalazine) and folic acid were characterized regarding their pharmacokinetic related properties (hydrophobicity, phospholipid and plasma protein binding) using the biomimetic chromatographic approach. Despite the high binding percentage of 5-aminosalicylates for human serum albumin (> 61.44%), results have shown that folic acid binding to human serum albumin protein is far greater (69.40%) compared to α1-acid-glycoprotein (3.45%). Frontal analysis and zonal elution studies were conducted to provide an insight into the binding of folic acid to human serum albumin and potential competition with 5-aminosalicylates. The analytical method for the simultaneous determination of assay in proposed fxed-dose combinations was developed and validated according to ICH Q2 (R1) and FDA method validation guidelines. Separation of all compounds was achieved within 16 min with satisfactory resolution (Rs> 3.67) using the XBridge Phenyl column (150 × 4.6 mm, 3.5 µm). High linearity (r> 0.9997) and precision (RSD< 2.29%) was obtained, whilst all recoveries were within the regulatory defned range by British (100.0± 5.0%) and United States Pharmacopeia (100.0 ± 10.0%).

HPLC ; biomimetic chromatography ; assay

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