Biowaiver monograph for immediate-release solid oral dosage forms: Dabigatran etexilate.

The feasibility of applying a biowaiver based on Biopharmaceutics Classification System (BCS) to immediate-release oral capsules containing dabigatran etexilate was evaluated according to the ICH M9 guideline. Based on literature data and experimental results, the Dose/Solubility ratio of the drug substance does not meet the criteria for "highly soluble" at pH ≥ 4.5, it is classified as "low solubility" according to the ICH M9 guideline. Likewise, dissolution testing of the comparator product, Prazaxa®, revealed that it fails to satisfy the guideline criteria for "rapidly dissolving" formulations (≥ 85% dissolution within 30 minutes) at either pH 4.5 or 6.8. Mass balance studies indicated that it possesses "low permeability." Together, these findings classify dabigatran etexilate as BCS Class IV. The need to generate an acidic microenvironment using organic acids to achieve adequate absorption suggests a high likelihood that differences in excipient composition could affect bioequivalence (BE). From a clinical perspective, fluctuations in systemic exposure may significantly impact both efficacy and safety. Considering its physicochemical properties, formulation-dependent characteristics and inherent clinical risks, application of a BCS-based biowaiver to solid oral dosage forms of dabigatran etexilate cannot be recommended. Accordingly, demonstration of bioequivalence through in vivo BE studies remains necessary for regulatory approval.