Supersaturated Silica-Lipid Hybrid Oral Drug Delivery Systems: Balancing Drug Loading and In Vivo Performance

Abstract

Supersaturated silica-lipid hybrid (super-SLH) drug carriers are a recent strategy to improve the drug loading of oral solid lipid based formulations, however they are yet to be studied in vivo. This study investigated the in vivo pharmacokinetics (PK) of super-SLH containing ibuprofen (IBU), as a model Biopharmaceutics Classification Scheme (BCS) class II drug, analyzing the influence of supersaturated drug loading on oral bioavailability and assessing in vitro-in vivo correlation (IVIVC). In addition, super-SLH was directly compared with spray-dried SLH and Nurofen to explore its potential advantages over the well-established and commercial formulations. Fasted male Sprague-Dawley rats were administered formulation suspensions (10 mg/kg IBU) via oral gavage, and blood samples were acquired and plasma was analyzed for IBU concentrations over 24 hours. In vivo, super-SLH with drug loads of 9.5 (99.5% saturated) and 19.3% w/w (227% saturated) achieved bioavailabilities equal to spray-dried SLH and 2.2-fold greater than Nurofen. This effect diminished for super-SLH with a drug load of 29.1% w/w (389% saturated), which exhibited a bioavailability of less than Nurofen due to its greater extent of supersaturation and larger content of crystalline IBU. The super-SLH containing 19.3% w/w IBU provided the greatest PK performance, achieving the same degree of bioavailability enhancement as spray-dried SLH and requiring 63% less formulation. A significant positive IVIVC was observed between the performances of the formulations. These findings indicate the potential of super-SLH as an improved oral solid lipid based formulation strategy for enhancing oral bioavailability of other BCS class II drugs.