Preparation and evaluation of ibrutinib lipid-based formulations

Abstract

Ibrutinib is an anti-cancer drug, mainly used for treating B-cell malignancies. Because of its low water solubility and poor absorption in vivo, the bioavailability is extremely low, only 2.9%. In this study, a solid self-microemulsifying drug delivery system based on the lipid matrix was designed and prepared for ibrutinib. The composition of the self-microemulsion of ibrutinib includes oil phase Caprylic/Capric Triglyceride (Captex®335), surfactant Tween-80, and co-surfactant Diethylene glycol monoethyl ether (Transcutol HP). And the mesoporous silica SBA-15 was selected as an adsorbent to prepare solid powder preparations using the spray-drying method, which significantly improved its dispersibility and stability, and contributed to reducing the particle size and long-term preservation in gastric and intestinal fluids. The in vivo pharmacokinetic study of beagles showed that compared with commercial ibrutinib capsules, the relative oral bioavailability of ibrutinib capsules based on lipid matrix increased to 467.60%. In summary, the lipid-based solid preparation is a promising platform that can effectively improve the oral absorption of ibrutinib.