Porous polymer improves asthma drug delivery
improve the delivery of a range of drugs, including those that are
poorly-soluble in water. The technology is being used to develop a
sustained-release version of an inhaled drug for asthma, doing away
with the need for multiple inhalations each day.
The patent (No 6,730,322) covers the company's porous microparticle technology, which can be used to create slowly-dissolving shell materials to create sustained-release formulations of a variety of drugs. These formulations have the potential to release drugs over periods ranging from days to weeks by intravenous, inhalation, subcutaneous or oral routes of administration.
"It is difficult to create sustained release formulations for many hydrophobic drugs because they release too slowly from the microparticles used to deliver the drug, diminishing the efficacy of the delivery system," said Acusphere, which estimates that hydrophobic drugs generated $120 billion (€99bn) in worldwide revenue in 2002.
To tackle the problem, Acusphere has developed a process by which the water uptake into polymer microparticles can be altered. This can speed the release of the active drug, while retaining the desired sustained release profile of these drugs. The company says it can alter the porosity of the microparticles during manufacturing via the selection of additional materials to include in the microparticle shell, such as lipids or other hydrophobic compounds.
Acusphere is currently using this patented technology to develop AI-128, a sustained release formulation of a hydrophobic, inhaled corticosteroid. AI-128 is designed to slowly release the drug locally into the lungs so that it has the potential to reduce the multi-dosing per day regimen to a longer-lasting, once per day regimen which should improve patient compliance.
In a human study, AI-128 delivered the drug over the 12-24 hour period Acusphere believes is necessary for once per day dosing. In addition, AI-128 delivered a lower concentration of the drug into the systemic circulation relative to the FDA-approved formulation of this inhaled corticosteroid, demonstrating the potential for an improved safety profile.
Many of the leading asthma drugs, including most inhaled corticosteroids, are hydrophobic drugs, and global revenues for inhaled corticosteroids exceeded $6 billion in 2003. Most of these corticosteroids are administered multiple times per day and, as a result, patient compliance can be a problem that may lead to acute asthma attacks and resultant emergency room visits and hospitalisations.
And although inhaled corticosteroids are intended for local delivery to the lung, commercial formulations deliver some of the drug unintentionally into the systemic circulation, where the drug may have undesirable side effects. These side effects include the slowing of bone growth that can stunt growth in children. As a result, many physicians are hesitant to prescribe these inhaled corticosteroids to children.
In addition to altering the release characteristics of the matrix, its surface properties can be modified to improve the targetting of drug release. For example, adhesion to tissues in the body can be enhanced through the selection of bioadhesive polymers, which may be particularly desirable when the matrix is in the form of microparticles administered to a mucosal surface such as in intranasal, pulmonary, vaginal, or oral administration.
Targeting can also be achieved by selection of the polymer or incorporation within or coupling to the polymer to structures which specifically bind to particular tissue types or cell surface molecules such as receptors.
This patent is the third in a series of patents issued to Acusphere related to certain porous microparticle compositions for sustained release formulations, their use and method of production.
