A predictive release kinetic model guiding the rational design of sustained release solid dispersions with insoluble...

Flurbiprofen (FBU) is a nonsteroidal anti-inflammatory drug with short half-life, requiring frequent dosing and leading to potential gastrointestinal side effects. To address these limitations, this study aimed to develop the FBU sustained release solid dispersion using insoluble carriers (Eudragit RL100/RS100). The release kinetics of various formulations were investigated, and the release mechanisms were analyzed using an internal and external diffusion kinetic model. The powder X-ray diffraction and differential scanning calorimetry results confirmed the amorphous nature of FBU in all solid dispersions. It was found that the formulation composition significantly influenced the release kinetics, where low permeable Eudragit RS slowed the release and the incorporation of the soluble polymer PVP enhanced it. An optimized formulation with 10% PVP achieved nearly complete release with desirable sustained release characteristics. The kinetic model successfully modeled the release profiles with a maximum average relative deviation (ARD) of 11.8%, revealing that the release was predominantly controlled by internal diffusion. The model was further utilized to predict the release behavior for varying carrier compositions and particle sizes successfully, demonstrating its ability in guiding the rational design of formulations based on insoluble polymeric carriers. This work underscores the critical role of mechanistic modeling in transitioning from empirical formulation screening to rational design.