Mathematical modelling of drug release from lipid based FluidCrystal® systems

Sammanfattning

In recent years, long-acting drugs have emerged as a significant advancement in the treatment of chronic diseases. Camurus is a pharmaceutical company specializing in this area, with products based on FluidCrystal® technology—a lipid-based injectable drug delivery technology that, upon contact with water or physiological fluids, undergoes a phase transition into a liquid crystalline gel depot. Drug release from the depot is governed by a combination of diffusion and surface erosion. In vivo, surface erosion is driven by enzymatic degradation, while in vitro, surfactants are used to mimic this process. Mathematical modelling has become an increasingly valuable tool in drug delivery research, offering a way to reduce experimental workload and optimize formulation development. The aim of this thesis is to improve understanding of the release behavior of the FluidCrystal® technology by developing a mathematical model based on a modified version of the diffusion–erosion model proposed by Stiepel et al., specifically adapted to describe surfactant-dependent in vitro release. A new erosion model inspired by the Nernst–Brunner equation was developed, incorporating both time- dependent surface area, a solubility term dependent on surfactant concentration and agitation dependent mass transfer. The model was successfully implemented and showed good predictive performance across depots of varying sizes. Its core parameters—the mass transfer coefficient and the initial solubility—were further estimated under different experimental conditions to allow prediction under varying formulation and agitation setups. The resulting model can support formulation development by enabling prediction of release profiles under different laboratory conditions, potentially reducing experimental workload. The model provides Camurus with a broader understanding of their in vitro release behavior.