PPI Pipeline

PPI-1501: Low Dose Effective Analgesia with Enhanced Opioid Sparing

PPI-1501 is the first intravenous formulation of the internationally approved highly potent yet highly insoluble NSAID Flurbiprofen. In tablet form Flurbiprofen is indicated in North America and Europe for arthritis and in the UK for postoperative pain. Until now the insolubility of Flurbiprofen has previously prevented its repurposing as a parenteral formulation.

In Japan, a novel pro-drug of Flurbrofen (flurbiprofen axetil; Ropion ® Kaken Pharmaceuticals) has been developed to overcome insolubility. This new chemical entity (NCE) has been used successfully to treat postoperative pain although despite modification and reformulation it still requires lipid excipients, dilution and large volume administration. Like all prodrugs Ropion displays high inter-patient variability and it is not approved in Europe or North America.

Clinical Advantages of PPI-1501

Unlike large volume products such as Ofirmev or Caldolor that are infused over extended periods PPI-1501 may be administered rapidly as a 1mL bolus injection. Such rapid administration allows lower costs for the hospital, preferable for the patient and allows higher blood levels to be reached than slow infusions, thereby promoting a fast onset of action.

Most importantly, the unique micellar structure of SmartCelle technology enables considerable increases in exposure to Flurbiprofen from a single injection, slowing the elimination of the drug from the body and maintaining blood concentrations above therapeutic minimums for twice as long as a low concentration conventional formulation and the pro-drug flurbiprofen axetil. Such features enable reduced frequency dosing, an improved side-effect profile and an enhanced effect on opioid sparing.

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Pharmacokinetics of 100mg of flurbiprofen as delivered Q12h by SmartCelle technology (FLU PPI); a simple conventional technology (FLU Solution); or by the pro-drug Flurbiprofen Axetil (FA). Note that therapeutic levels (4 mg/L – dotted blue line) of flurbiprofen are reached immediately by FLU PPI but that peak concentrations are lower than the FLU solution. Note also that therapeutic levels are maintained for over 12hrs by the SmartCelle formulation halving the required re-administration time and increasing exposure over 2 fold; the chance of breakthrough pain during the first hours of treatment are diminished. Such features may enable a significantly improved safety profile and an enhanced opioid sparing effect.

 

 

Physicochemical Properties.

Unlike products such as Toradol and Dyloject PPI-1501 is a highly stable, even at elevated temperatures.

Unlike pro-drugs that may be expensive to develop and register, PPI-1501 comprising safe and effective NSAID Flurbiprofen has a straightforward cost-effective development path.

PPI-1601:

A novel high dose, low volume injectable micellar Celecoxib formulation for postoperative pain again enabled by SmartCelle’s unique pharmacokinetic properties.

PPI-1602:

An improved lower volume low viscosity injectable acetaminophen formulation for treatment of postoperative pain enabling sustained blood concentrations.

 

PPI-1401:

A novel lipid and preservative free, low pain on injection propofol formulation for the induction and maintenance of anaesthesia