A phase 0 clinical trial of novel candidate extended-release formulations of capecitabine

Purpose: To examine the pharmacokinetic (PK) profile of several candidate extended-release (ER) formulations of capecitabine in patients. Methods: In a phase 0 clinical study, PK profiles of several oral candidate ER formulations of capecitabine were compared to the PK profile of capecitabine after administration of the commercially available immediate-release (IR) tablet. A single dose of 1000 mg IR formulation (two 500 mg tablets) was administered on day 1, and a single dose of a 1000 mg candidate ER formulation of capecitabine (two 500 mg tablets) was administered on day 2. Candidate ER formulations of capecitabine differed with regard to the amount of the ER excipient (Kollidon^® SR) in tablet matrix (0–5 % w/w) and coating (0–12 mg/cm²). Results: PK profiles of nine different candidate ER formulations were examined. The tablet coating seemed the main determinant for ER of capecitabine and tablet integrity. Average (±standard deviation) AUC_0–2h, relative to AUC_0–2h after oral administration of the IR tablet, were 43.3 % (±34.9 %) and 1.2 % (±1.2 %) for candidate ER formulations coated with 3 and 6 mg/cm², respectively. Corresponding AUC_0–last were 93.6 % (±40.2 %) and 44.0 % (±5.4 %). Conclusion: Modulation of capecitabine release in patients can be accomplished by varying tablet coating content. Proof of principle was demonstrated for candidate ER formulations with coating content of 3 mg/cm².