Background In a double-blind, breast cancer chemoprevention trial in young female subjects with a genetic predisposition (BRCA1\2 mutation), the Hospital Pharmacy of the European Institute of Oncology developed a fenretinide formulation (not commercially available retinoid). The formulation consists in an oily microdispersion of fenretinide, encapsuled in Licaps by an automatic capsule filling and sealing system called CFS1200®.

Purpose The aim of this study is to demonstrate the chemical stability of the formulation for 18 months.

Materials and methods Hygroscopicity test, test for mechanical strength, dissolution test up to six months and content uniformity test at 6,12 and 18 months by HPLC/UV (capsules have been stored at room temperature in open bottles) have been performed. The HPLC/UV method is described below: -Operating temperature=15°C; -Column=Agilent Zorbax Eclipse XDB C18-150*4.6-5 μm; -Mobile phase A= methanol-water-acetic acid(700:300:3); -Mobile Phase B= methanol-water-acetic acid(950:50:3); -Gradient: start at 15% of mobile phase B; 40 min=100% mobile phase B; -Acquisition-time: 50 minutes; -Reconditioning-time: 10 minutes; -Flow rate: 1, 5 ml/min; -λ=35 nm; -Loop: 10 microlitres.

Results Hygroscopicity tests (water exchange at different RH) and mechanical strength test gave results in accordance with the specifications. The use of pepsin in dissolution medium made it possible to overcome the cross-linking issue between excipients and the gelatin capsule shell. The final results of the dissolution test after 6 months of storage were within specifications. The HPLC/UV method is robust and accurate. Linear responses were obtained in the considered concentration range(r²=0.99). The chromatogram contains up to 11 integrable peaks, of which the largest one is fenretinide (peak 9), peaks 7,8 and 11 are known impurities, while the sum of all the other impurities is 0,158%. There was no significant difference between the average concentration of the analyte in the capsules at 18 months(98.43%), and the fresh internal standard (quantitative deviation=4.82%).

Conclusions In oil fenretinide microdispersion, encapsulated in a nitrogen atmosphere using CFS1200® technology, is stable for at least 18 months.