Mucoadhesive thermoreversible formulation of metoclopramide for rectal administration: a promising strategy for potential management of chemotherapy-induced nausea and vomiting.

The study aimed to investigate the feasibility of incorporation of metoclopramide hydrochloride (MCP HCl) in mucoadhesive thermoreversible liquid suppository (MCP HCl) to bypass the first-pass metabolism and maximize its efficacy to be a promising substitute for parenteral therapy. MCP HCl was formulated using Pluronic (PF127/PF68) and hydroxypropylmethylcellulose (HPMC) and in vitro evaluated through their gelation temperature, gel strength (GS), mucoadhesive force, and in vitro release studies. Also, the MCP HCl was evaluated for its rheological behavior and examined for rectal mucosal integrity after administration. The results revealed that the MCP HCl; composed of PF127/PF68/HPMC (20/7/0.5% w/w) was in the liquid state at room temperature, experienced gelation at 30.23 °C, with suitable GS of 28.66 s and rectal retention force of 43.03 × 10 dyne/cm. The pharmacokinetic data showed that the MCP HCl exhibited a significant increase ( < 0.05) in AUC (219.688 vs 172.333 ng.h.mL of the marketed) and 1.3-fold increase in relative bioavailability compared to Primperan suppository, indicating that LS formula bypassed the first-pass metabolism. Moreover, MCP HCl did not cause any morphological harm to the rectal tissues suggested that the developed formulation was safe and could be a potentially useful alternative drug carrier for rectal delivery of MCP HCl in patients experiencing chemotherapy-induced nausea and vomiting.