Captisol hikes budesonide delivery to lungs
solubility technology developed by US company CyDex, has
outperformed one of the leading drugs for asthma on the market in a
preclinical study.
The inhaled version of budesonide made using CyDex' Captisol (a polyanionic beta-cyclodextrin) excipient - designed to improve the solubility and stability of active pharmaceutical ingredients (APIs) - could reduce the time it takes patients to receive nebulised asthma drugs from the current five to 10 minutes. This could be a significant advantage, particularly when trying to dose small children with the disease.
To date, Captisol has been used mainly to improve oral or parenterally-administered drugs, but the new study presented at the Respiratory Drug Delivery IX Conference in Palm Desert, US, provides the first proof-of-principle evidence that it can also improve the delivery of respiratory medicines.
The study compared the delivery of Pulmicort Respules (budesonide inhalation suspension), an AstraZeneca brand, and a 5 per cent Captisol and budesonide solution prepared by CyDex. Using four different nebulising devices, the amount of Captisol/budesonide delivered in each case was significantly higher than the amount of Pulmicort suspension.
In an air jet nebuliser, the device specified in the prescribing information of Pulmicort Respules, the mean emitted dose of Captisol-enabled budesonide was 44 per cent higher than the marketed suspension form.
And in three ultrasonic nebulisers, which are smaller and generally faster than air jets in delivering drug dosages, the emitted dose of Captisol/budesonide ranged from 111 per cent to 267 per cent greater than Pulmicort Respules.
CyDex noted that the package insert of Pulmicort Respules limits administration to air jet devices and notes that the suspension is not for use with ultrasonic devices. "However, the Captisol-enabled budesonide data indicate a strong potential for delivering therapeutic doses via the newer ultrasonic devices," according to the firm.
In addition, the study compared the distribution of particles delivered with Captisol-enabled budesonide compared to Pulmicort Respules. Using either a standard air jet or an ultrasonic nebuliser, the Captisol-Enabled solution delivered a larger proportion of the steroid in finer particles than the suspension.
While the clinical significance of this has not been established, it might suggest that the drug could be deposited deeper into the lungs, and so provide better control of asthma symptoms.
Captisol is already used in two approved and marketed Pfizer drugs, the antifungal Vfend (voriconazole) and an intramuscular formulation of ziprasidone, used to treat schizophrenia.
The technology works by forming complexes with water-insoluble drugs, making them water-soluble. In oral formulations, Captisol can improve bioavailability by improving the solubility and dissolution of drug compounds. When given by injection, a Captisol-enabled formulation helps carry a drug into the patient's bloodstream, where the excipient and the drug dissociate, allowing the active ingredient to produce its desired pharmacological effect.
