Self‐microemulsifying drug delivery system‐based gastroretentive in situ raft of pazopanib with enhanced solubility and bioavailability

Abstract Pazopanib hydrochloride (PZH) is a Biopharmaceutics Classification System class II drug that faces challenges at the formulation forefront including low aqueous solubility (0.043 mg/mL) and poor oral bioavailability (14–39%). The present investigation aimed to develop a self‐microemulsifying drug delivery system (SMEDDS) of PZH using a blend of Capryol® 90, Labrasol®, and propylene glycol to improve its solubility. Furthermore, a sustained‐release SMEDDS‐based gastroretentive floating system was developed and optimized using the Central Composite Design approach of DoE. The optimized SMEDDS‐based in situ gelling raft, R‐SM‐PZH, exhibited minimal floating lag time (3.09 ± 0.8 s), optimal viscosity (1229.4 ± 20.9 cP) and density (0.327 ± 0.15 g/mL) as compared to other formulations under study. Additionally, R‐SM‐PZH was evaluated for its in vitro dissolution in FaSSGF and FeSSGF, pharmacokinetic profile, and MTT assay (against NCI‐H460 lung cancer cells) compared to pure PZH. A 12 h sustained release, three‐fold augmentation in dissolution rate and bioavailability, and 15‐fold enhancement in cytotoxicity were observed in comparison to pure PZH. Thus, the SMEDDS‐based in situ gelling raft presents a promising approach to advancing the developability potential of PZH.