A paper published in Pharmaceutics describes development and validation of a production process for 5 mg tablets of infliximab, using biosimilar CT-P13 (Remsima, Inflectra), for the treatment of inflammatory bowel disease.
The oral delivery of biologic drugs represents an as-yet unattained goal. However, the potential benefits of oral administration of these therapies in terms of compliance, comfort, and drug storage are many, and several drug makers are pursuing the possibility: Last year, Amgen and Entera Bio announced a research collaboration into oral administration of biologics, and Protalix BioTherapeutics announced positive results from a study on oral administration of anti—tumor necrosis factor (anti-TNF) therapies.
Now, a paper published in Pharmaceutics describes development and validation of a production process for 5 mg tablets of infliximab, using biosimilar CT-P13 (Remsima, Inflectra), for the treatment of inflammatory bowel disease (IBD).
The authors of the paper hypothesized that, in IBD, targeting infliximab administration to the ileo-colonic region could be efficacious in treating local IBD inflammation.
The researchers used the biosimilar infliximab and reconstituted it into a sugar solution that, when lyophilized, yielded powder that could be further compounded and treated with a coating.
The coating technology (called ColoPulse) used on the tablets has a pH sensitive polymer; the intraluminal pH of the gastrointestinal tract rises during transit from the jejunum to the ileum, then drops in the colon, and the tablet’s coating uses this period of pH increase to disintegrate in the terminal ileum.
According to the researchers, the in vitro stability of infliximab in simulated gastrointestinal systems is “encouraging,” and analyses of infliximab content, tertiary protein structure, aggregates, and potency showed that the infliximab present in the coated tablet was stable during compounding and could bind to TNF.
Stability data showed that the preparation was stable for up to 6 months at 25°C.
The authors note that a clinical trial will be necessary to determine the such factors as the pharmacokinetics of the proposed coated tablet, as well as the potential for development of anti-drug antibodies.
Gareb B, Posthumus S, Beugeling M, et al. Towards the oral treatment of ileo-colonic inflammatory bowel disease with infliximab tablets: development and validation of the production process. Pharmaceutics. 2019;11(9):428. doi: 10.3390/pharmaceutics11090428.