Drug delivery


Often drugs have been designed for oral administration, so the ingredients of it may not be suitable for long- term injectables.


medicines live up to their current promise, we will see human trials for each of them in coming years. He also believes there are “huge opportunities for non-communicable diseases.” They could be used to prevent cardiovascular diseases, for example, or for central nervous system conditions. Even so, there are challenges. “Changing the route of administration from oral to parenteral means that the safety at the site of administration needs to be carefully assessed,” Owen says. “Only highly potent drugs are applicable for these approaches, because low drug concentrations in the blood are easier to achieve for long periods of time. Also, repurposed drugs were often chemically designed specifically for oral administration, meaning the chemistry of the molecule may not be ideal for a long-acting approach.”


A risk of developing drug resistance An added difficulty relates to implementation. While Ramazani believes that in the future, patients may be able to self- administer the long-acting medication, at present, LAIs are generally administered by a healthcare professional. “The durations of drug exposure should optimally fit with routine clinic visits for the specific disease, so that additional clinic visits are not needed,” Owen says. There is always a risk, he adds, that if a patient has a chronic infectious disease, but doesn’t return to the clinic for their scheduled dose, there may be a higher risk of developing drug resistance – an eventuality Owen refers to as “the long tail of suboptimal exposure”. Education, he says, will be important, and any patient who decides to stop taking a long-acting medicine will need to return quickly to their oral regimens. In future, we may see pharma companies


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investing in the development of LAIs from scratch. Currently, many are reluctant to do so, for understandable reasons. “If you have a new molecule and you don’t know if it will work, it’s a lot of investment,” says Ramazani. “Developing the long-acting injectable costs lots of money, especially in the early stages of development.” For instance, clinical trials need to run for longer to make sure the drug is safe and effective. “Then we have the high risk of failure for the project, maybe 80%, when they enter the clinical trial phrase,” he says. With injections, he adds, there can be “local tolerability issues,” including inflammation, or even, in the worst cases, necrosis and tissue damage, all of which means that a cautious approach is required. “It’s not easy to convince the managers to go in this direction,” he adds. An alternative approach, Ramazani suggests, might be to develop a molecule for oral administration and carry out clinical trials to test whether it works, while developing the long-acting formulation in parallel to save time and money. There is good reason, however, to believe that the future of long-acting injectables is assured. The technical complexities, and the related higher costs, are likely to diminish as the scale of applications increases, Owen says. Because a lower overall drug dose is needed for a long-acting approach than for an orally-delivered counterpart, he adds, that is likely to reduce costs too. The main reason that they are likely to be adopted is that all stakeholders – pharma companies, patients and health care providers – see benefits. “Pharma companies are demonstrating their apparent appetite for the approach through the depth of investment they are making in development,” he says. “Patients overwhelmingly see the benefits for long-acting medicines, and surveys have consistently demonstrated high enthusiasm for the approaches from patients and providers.” ●


World Pharmaceutical Frontiers / www.worldpharmaceuticals.net


Zyn Chakrapong; Krzysztof Bubel/www.shutterstock.com


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