engleski

Immunosuppressive therapy for IBD patients: time for an improved approach?

Inflammatory bowel diseases (IBD), which comprise of the two major clinical subtypes, Crohn's disease and ulcerative colitis, are relapsing systemic inflammatory diseases, mainly affecting the gastrointestinal tract with extraintestinal manifestations and associated immune disorders. Both subtypes are characterized by unpredictable course, with periods of flare-ups and remissions suggesting poor adherence to medical therapy. Immunosuppressants, azathioprine, 6- mercaptopurine and 6-thioguanine, are the most prescribed drug class in IBD treatment as steroid-sparing therapy, effective in maintaining remission. The inflammatory process along the digestive tract disrupts absorption of vitamins ; thus, the additional supplementation of IBD patients with vitamins is recommended. Moreover, low folate intake has been associated with tumor growth in IBD. Consequently, a number of IBD patients take folic acid with imunosuppressive drugs. Still, fixed-dose combinations of IBD drugs and folic acid are not available on market. Therefore, the development of such formulation, as well as analytical support for quality control investigation, is of exceptional importance. Investigation of ADME properties is an integral part of novel drug and formulation development. In silico approach, a fast developing technique for ADME prediction, has been used to give insight into compatibility of APIs in proposed fixed-dose combinations. Furthermore, chromatography (C18-HPLC and IAM- HPLC) has been successfully used in ADME modeling. Finally, a fast and reliable HPLC/DAD/MSn method for simultaneous determination of all APIs has been developed and validated. Various combinations of commonly used excipients were tested in the formulation optimization. The proposed method has been applied for analysis of commercially available products and proposed fixed-dose combinations. Acknowledgment This work has been supported in part by the Croatian Science Foundation under the project number [UIP-2017-05-3949].

Immunosuppressive therapy ; IBD ; HPLC ; IAM ; ADME

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