Injectable asthma formulation uses Captisol technology

The US-based biopharmaceutical company announced it was signing a license and supply agreement with specialty pharmaceutical drug delivery company CyDex for exclusive worldwide rights to its Captisol enabling technology. The technology would be used to develop an injectable formulation of zileuton for the treatment of asthma, which would be expected to enter Phase II clinical trials in the second half of this year. Critical Therapeutics, and its co-promotion partner Dey, currently markets asthma drug Zyflo (zileuton tablets) and received approval from the US Food and Drug Administration (FDA) last month for Zyflo CR (zileuton) extended-release tablets, which it hopes to market later this year. Now the company is looking to develop an injectable formulation for use in the emergency room for patients who are experiencing acute exacerbations of asthma. An injectable formulation would be a quick way to resolve the asthma exacerbations while removing the negatives of steroid-based treatments. Being an insoluble molecule, zileuton would need to overcome this obstacle to be injectable, which is where CyDex's Captisol technology comes in to play. The technology improves water solubility, bioavailability and complexation characteristics of insoluble or unstable drugs. Based on a polyanionic B-cyclodextrin derivative, Captisol is a molecule which has a water loving and a water hating end. It can create a donut-like shape with the hydrophobic end on the inside which provides an environment suitable for insoluble drugs. Speaking to US-PharmaTechnologist.com, CyDex chief executive John Siebert said a molecule which was normally insoluble would become soluble in this environment. "It allows for a lot of drug formulations that wouldn't normally be put together without the use of this technology." ​ Once in the blood, the particles are diluted out and the drugs are released from the core. In the case of Zileuton, "using Captisol was the safest and easiest way to make an injectable solution",​ Siebert said. Critical Therapeutics expects to initiate a Phase II clinical trial for the injectable formulation of zileuton in the second half of this year, following favorable results from an earlier clinical trial in asthma patients. The Phase II trial would be focused on identifying the optimal dose to be tested in Phase III trials. Zyflo and Zyflo CR are the only FDA-approved leukotriene synthesis inhibitors for prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. The drugs are indicated for use in the reversal of bronchospasm in acute asthma attacks. There are currently four injectable drugs on the market which utilize the Captisol technology. Pfizer has three of those: Vfend (voriconazole) an antifungal, Geodon (ziprasidone), a tranquilizer and veterinary product Cerenia. The fourth drug is tranquilizer Abilify (aripiprazole) from Bristol-Myers Squibb. Last month, Sunesis Pharmaceuticals and Proteolix both signed licensing agreements for Captisol technology for the development of new drug formulations.