Children and adults with certain medical conditions often have trouble swallowing pills. To help them take their medicines, caregivers sometimes mix the drugs in liquid to make a syrup or solution. However, crushing tablets and turning them into a slurry is often messy and makes accurate dosing tricky, and some medications can be harmful or even cause overdose if crushed or modified from their original forms.
To offer an easy-to-swallow solution, scientists at the Massachusetts Institute of Technology (MIT) developed an oil-based gel dubbed oleogel to formulate both water-soluble and insoluble drugs. They published their work in Science Advances (1).
The design of the gel “is inspired by advances in the food industry,” said Giovanni Traverso, a mechanical engineer at MIT and a gastroenterologist at Brigham and Women’s Hospital who led this research. “There have been significant developments in stabilizing, for example, chocolates for warm weather, as well as ice creams for warmer climates,” he said. “Through that knowledge, we developed this oleogel platform, and we're able to create anything from a gel-like consistency all the way to a gummy-like consistency.”
Using the oleogel approach, the scientists can make medicine easier to administer in resource-constrained settings where clean water may be scarce and more heat-stable for long-term storage where there is no access to refrigeration.
While liquid-based formulations are common, oil-based oral gels are not widely available (2). Ameya Kirtane, a pharmaceutical scientist at MIT at the time of the study and coauthor of the article began the study by asking: “How do we actually change an oil, which is a liquid, into a gel — something that doesn't flow. And how can you manipulate the textures of these gels by adding different components to it?”
The team pinned down a few criteria. To be useful, the oleogel should be able to deliver both hydrophobic and hydrophilic drugs. It should not require the patient to swallow a large solid nor require any reconstitution. And it should be safe for children.
To make these oleogels, the scientists mixed-and-matched four edible ingredients: an oil, a gelling agent, a solubilizer, and a drug. They picked edible gelling agents such as beeswax and rice bran wax to adjust the consistency of a variety of cooking oils. They also selected FDA-approved solubilizing agents, which are fatty acid esters, to dissolve the drugs.
Once the scientists identified the combination of ingredients to use, the gel itself was relatively easy to make. “We take the oils. We heat them up. We stir them. We take these mixers, and then we just cool them down. It is that simple,” Traverso said.
The scientists selected commonly used anti-infectives for children to formulate into oleogels. “Our primary goal was to apply this in children in developing countries, and the major disease areas affecting these children are infectious diseases,” said Kirtane. They tested the antibiotic azithromycin, the anti-parasite praziquantel, and the anti-malarial lumefantrine, which are all hydrophobic.
As a proof of concept, the team tested the drug loaded oleogels in pigs because of their similarities in body size to humans. They found that the oleogels delivered the three drugs better than their original tablet formulations did. The scientists also tested a water-soluble antibiotic, moxifloxacin, which they made into a paste, which also worked well in pigs.
Aside from the chemical and physical properties of the gels, the scientists wanted to know how the gels taste. “Children are very picky eaters, so we wanted to make sure that it's something that doesn't taste too bad,” Kirtane said.
To nail the texture and flavor profiles, the scientists turned to Sensory Spectrum, a company that specializes in generating sensory information about products.
“We iteratively screened through the samples and started to understand flavor and texture characteristics,” said Katelyn Booz, a project manager at Sensory Spectrum who worked directly with the scientists.
In generating a sensory report for the oleogel, Booz assembled a panel of taste experts who described the gel as smoky, nutty, waxy, chalky, and floral. The different oil and gelling agent combinations gave different texture and taste profiles. Gels made with sesame oil, for example, had a sweet and nutty note, whereas gels made with candelilla wax were bitter.
While the scientists designed the oleogels for children, they have only recruited adult testers for the analysis.
Margaret Scheffler, a pediatric intensivist at Brown University who has worked with children in an under-resourced area of Lesotho and who was not involved in the study, stressed that a drug formulation that is shelf stable, does not require refrigeration or reconstitution, and can be packaged easily, “is worth its weight in gold.”
The oleogel formulation offers more user-friendly packaging and dosing compared to a liquid formulation, according to Scheffler. “You can imagine your own experience of buying cough syrup at the pharmacy. You bring it home, you pour it into that little cup, and how much of that little cup actually gets in my mouth? But with a gel or a paste, you are able to actually squeeze a pouch and then see the pouch flat or empty,” she said.
While Scheffler said that the development is “very exciting,” this research is still at a very early stage.
Optimizing drug concentrations in these oleogels could be a potential challenge. “It's not clear yet if we're going to be able to pack the same amount of drug into a similar volume of these gels as we're able to pack into a volume of liquid,” said Scheffler. Ensuring that the drug still retains its effectiveness in the human body is also important.
“Tablets are generally formulated with adult dosages in mind,” said Scheffler. To show that the formulation would work in children, the scientists would need to demonstrate that the drug concentration can reach the desired serum concentration that is effective against the infection.
“Our formulations seem to do well compared to commercial tablets, and that was really promising. Given that preliminary data, I'm hoping that we see something similar in people,” said Kirtane. The scientists have recently received FDA approval to run a phase I clinical trial for some of their drug loaded gel formulations and will continue their investigations in humans.
References
- Kirtane, A.R. et al. Development of oil-based gels as versatile drug delivery systems for pediatric applications. Sci Adv 8, eabm8478 (2022).
- O’ Sullivan, C.M. et al. Edible oleogels for the oral delivery of lipid soluble molecules: Composition and structural design considerations. Trends in Food Science & Technology 57, 59-73 (2016).
