For most children and even some adults, swallowing pills or tablets is difficult. To make administering these drugs easier, researchers at MIT and Brigham and Women’s Hospital have created a drug-delivering gel that is much easier to swallow and can be used to deliver different types of drugs.
The gels, made from vegetable oils such as sesame oil, can be made with a variety of textures, from a thickened drink to a yogurt-like substance. The gels are stable without refrigeration, which could make them easier for children in developing countries to access, but they could also benefit children anywhere, the researchers say. They might also help adults who have difficulty swallowing pills, such as the elderly or people who have had a stroke.
“This platform will change our ability to do what we can do for children, but also for adults who have difficulty receiving medication. Given the system’s simplicity and low cost, it could have a huge impact on making medication easier for patients,” says Giovanni Traverso, Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT, gastroenterologist at Brigham and Women’s Hospital, and the study’s lead author.
Traverso and his colleagues have shown that they can use the gels to deliver several types of drugs for the treatment of infectious diseases, at the same doses that can be delivered by pills or tablets, in animal studies. The research team is now planning a clinical trial which should begin within a few months.
Ameya Kirtane, former postdoc at MIT, now a teacher at Brigham and Women’s Hospital; Christina Karavasili, post-doctoral fellow at MIT; and former technical associate Aniket Wahane are lead authors of the study, which appears today in Scientists progress.
Easy to swallow
Almost 10 years ago, while working on other types of ingestible medication delivery systems, the research team began thinking about new ways to make it easier for children to take medication normally. administered in the form of pills. There are strategies that can help with this, but none are a perfect solution. Some antibiotics and other drugs can be suspended in water, but this requires clean water to be available and the drugs must be refrigerated after mixing. Also, this strategy does not work for drugs that are not water soluble.
With medications that are only available in pill form, healthcare providers can try dissolving them in water for children to drink, but this also requires a clean water supply, and dosages can be difficult to obtain correctly if the pills are for adults.
In an attempt to address these issues, researchers set out to develop a new drug delivery system that would be inexpensive, palatable, stable at extreme temperatures, and compatible with many different drugs. They also wanted to ensure that the drugs did not need to be mixed with water before dosing and that the system could be administered orally or as a suppository.
Because they wanted their formulation to work with drugs that cannot be dissolved in water, the researchers decided to focus on oil-based gels. Such gels, also called oleogels, are commonly used in the food industry to modify the texture of fatty foods, as well as to raise the melting point of chocolate and ice cream.
“This approach gave us the ability to deliver highly hydrophobic drugs that cannot be delivered by water-based systems,” says Kirtane. “It also allowed us to create these formulations with a very wide range of textures.”
Researchers explored several types of plant-derived oils, including sesame oil, cottonseed oil, and flaxseed oil. They combined the oils with edible gelling agents such as beeswax and rice bran wax, and discovered that they could achieve different textures depending on the concentration and type of oil and gelling agent. . Some gels end up having a texture similar to a thick drink, like a protein shake, while others are more like yogurt or pudding.
To identify the most palatable gels, the researchers worked with Sensory Spectrum, a consultancy specializing in consumer sensory experiences. Working with the company’s professionally trained taster panels, the researchers found that the most appealing gels included those made from oils with a neutral flavor (like cottonseed oil) or slightly nutty flavor (like sesame oil).
Deliver many medicines
The researchers chose to test their gels with three water-insoluble drugs from the World Health Organization’s list of essential medicines for children: praziquantel, used to treat parasitic infections; lumefantrine, used to treat malaria; and azithromycin, used to treat bacterial infections.
“Based on this list, infectious diseases really stood out in terms of what a country needs to protect its children,” says Kirtane. “A lot of the work we did in this study was focused on drugs for infectious diseases, but from a formulation perspective, it doesn’t matter what drug we put in those systems.”
For each of these drugs, the researchers found that the oleogels were able to deliver doses equal to or greater than the amounts that can be absorbed from the tablets, in animal tests. The researchers also showed that a water-soluble drug, an antibiotic called moxifloxacin hydrochloride, could be successfully delivered by an oleogel.
To make it possible to use these formulations in areas that may not have refrigeration, researchers designed them to be stable at 40 degrees Celsius (104 degrees Fahrenheit) for several weeks. and even up to 60 C (140 F) for a week. Such high temperatures are rare but can be reached when drugs are transported by trucks without refrigeration.
The researchers have obtained FDA approval to conduct a Phase I clinical trial of their olegel formulation of azithromycin, which they hope to initiate at the Brigham and Women’s Hospital Center for Clinical Investigation in the coming months.
To store and deliver the drugs, the researchers also designed a dispenser similar to a squeezable yogurt wrapper, with compartments that could be used to separate doses. This could make it easier to deliver the right dosage for each child, depending on their weight.
Other authors of the article include Dylan Freitas, Katelyn Booz, Dao Thi Hong Le, Tiffany Hua, Stephen Scala, Aaron Lopes, Kaitlyn Hess, Joy Collins, Siddharta Tamang, Keiko Ishida, Johannes Kuosmanen, Netra Unni Rajesh, Nhi Phan, Junwei Li, Annlyse Krogmann, Jochen Lennerz, Alison Hayward, and Robert Langer.
The research was funded by the Bill and Melinda Gates Foundation, a PhRMA Foundational Postdoctoral Fellowship, a Fulbright Fellowship, and the Koch Institute Support (core) grant from the National Cancer Institute.