INVENTION NOVELTY
This invention provides for novel formulations and delivery methods of the propofol prodrug, fospropofol, allowing for its use in additional indications beyond anesthesia, including migraine, analgesia, and emesis treatment.
VALUE PROPOSITION
Propofol and its water soluble prodrug, fospropofol, are short-acting anesthetics used for general anesthesia. Propofol has shown efficacy in a number of additional indications, including migraine, analgesia, and emesis. However, current intravenous formulations of propofol and fospropofol do not allow for their exploration and use in these alternative indications due to their short-acting properties. These novel delivery methods allow for direct and sustained drug delivery, enabling their use beyond general anesthesia. Intranasal fospropofol delivery allows for direct delivery of the prodrug to the brain, while buccal delivery allows for a sustained release of propofol, These administration routes provide unique exposure profiles ideal for treatment of a variety of neurological and psychiatric conditions
TECHNICAL DETAILS
Propofol is only available in an IV formulation due to its water insolubility. The prodrug fospropofol is water soluble, making it amenable to alternative formulations. Unexpectedly, intranasal and buccal formulations of fospropofol result in significantly different pharmacokinetic profiles. Intranasal delivery leads to appreciable concentrations of fospropofol in the plasma and cerebral spinal fluid, suggesting direct delivery to the brain. Buccal delivery provides a controlled, sustained delivery of propofol, with drug concentrations slowly rising over several hours following administration; 50 mg buccal fospropofol resulted in >400 nM propofol plasma concentration in monkey models.
