FORMULATION OPTIMIZATION AND CHARACTERIZATION OF NEWSTABLE READY TO USE (RTU) INJECTABLE FORMULATION OF ROCURONIUM BROMIDE

Commercially available injectable Rocuronium Bromide, a non-depolarizing neuromuscular blocker intended to store in a refrigerator at 2-8°C, requires an additional storage facility. The primary objectives of the present research were to design a stable, Ready to use (RTU) formulation of Rocuronium Bromide (RCB) Injection for Intravenous (IV) administration for storage at room temperature. Beta cyclodextrin (BCD) forms inclusion complexes with RCB. Edetate Disodium (EDTA) helps in achieving within the specification limit of Impurity C (Imp. C), a major metabolite of rocuronium bromide and Assay. Other excipients were selected to achieve a stable injectable formulation and cause less pain at the injection site. The formulation was optimized by Design of experiments (DoE) applying Central Composite Design (CCD) using Design Expert software and established design space where the formulation meets the desired acceptance criteria. The obtained optimized formulation can be terminally sterilized by moist heat and evaluated for thermal stability and robustness. The robustness of the formulation was established through Temperature excursion studies, pH sensitivity, and Oxygen sensitivity studies. Shelf life was estimated for 19 months when stored at 22°C which is an improvement to the currently available brands with 2-8°C storage. The formulation does not contain acetate buffer, which was identified as the root cause of the pain at the vascular site and may cause less vascular pain at the injection site. The current research work is encouraging in a positive way to achieve the objective of stable Rocuronium bromide injection at ambient conditions to enhance patient compliance.