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Inside the Science of Making a Better Pill

Turning the active ingredients of a medicine into a tablet or liquid that is effective, safe and convenient is a crucial step in the development of a medicine, and the complexity of the process is often veiled behind the tidy final product we see.

Having a medicine that is the right shape, taste, and color is intricately linked to how compliant people are with using them as directed — in terms of both dosage and timing — so getting this step right can significantly influence the medicine’s effectiveness.

That’s where scientists like Dr. Lourdes Contreras come in. 

Lourdes Contreras works in the Drug Product Design Department at Pfizer’s facility in Sandwich, United Kingdom. She’s an expert in the formulation of medicines and in designing the process by which they are manufactured.

Contreras, who works in the Drug Product Design Department at Pfizer’s facility in Sandwich, United Kingdom, is an expert in the formulation of medicines and in designing the process by which they are manufactured. “I’m trying to accelerate the development of new medicines, especially using new technologies,” she says of her role, adding that she’s trying to “get the medicines faster to the people who need it.” 

A major focus of Contreras’ work is on what is known as “multiparticulate systems”— that is, multiple units, normally spherical particles, that can enhance therapeutic objectives. These multiparticulate systems can be manufactured in different particle sizes. So, what’s the benefit of using multiparticulate systems and why is the particle size of a medicine important?

Multiparticulates under light microscopy.

How Particle Size Can Affect Medicines

Typical particle sizes of multiparticulate for medicines range from 100 microns to over a millimeter. Whether you need the medicine to be released slowly or quickly will often determine the inactive ingredients that the active ingredients are packaged with. 

One of the major benefits of a multiparticulate system is that it allows various options for controlling the release of a medicine in a person’s body, Contreras notes.

“By controlling the release, you can prevent the medicine from getting too concentrated in the stomach and that means you can potentially reduce the irritation,” she notes of the therapeutical advantages of these systems. “In many cases, we can deliver relatively high doses without having this issue of irritating the stomach.”

The ability to control the release of a medicine into a steady trickle also means people will likely not need to take it as often during the day, which can improve convenience and potentially compliance. Another advantage of a controlled-release formulation is that it avoids that initial spike of the medicine being delivered into the body, and avoiding that initial spike makes it safer.

Other advantages of multiparticulate systems include the ability to provide dosing accuracy and different methods of administration—for example, as a capsule filling, sprinkled in food, orally disintegrating tablets, or a sachet, which is a taste-masked solid suspended in liquid, such as powdered cold medicines that you mix into hot water.

 

Varying the particle size can also create good mouth feel and make it easier to swallow, says Contreras, who studied chemistry, pharmaceutical sciences and biologics at the Universidad Autonoma Metropolitana Xochimilco in Mexico City before obtaining her advanced degrees, including her Ph.D. in Pharmaceutical Technology at the University of Seville, in Spain, and the University of Basel, in Switzerland. 

Multiparticulates ranging in size from 150 to 425 microns in diameter.

“Some medicines are not very palatable. So, changing the taste helps us to minimize the issues with administering the medicine— not just for pediatric populations, but for adults and the elderly as well.”

Different cultures also have preferences for different types of formulations, such as in Mexico, Contreras’ home country, where some prefer chewable tablets. In Japan, many prefer orally disintegrating tablets. Chewables can nowadays be made with multiparticulates with a neutral taste mask, she notes. The neutral taste mask coatings prevent the medicines from being released in the mouth but then is released in in stomach acid.

The Challenge of Liquid Medicines

There are a number of hurdles that scientists need to overcome when delivering medicines in liquid form rather than in a tablet, including the fact that liquid medicines are often used for children. 

“A few challenges with liquid formulations are the difficulty in providing controlled-release delivery, masking the bad taste that some liquid formulations have and, additionally, the stability, as most of them are required to be refrigerated,” Contreras says, noting liquid formulations need preservatives—something that’s mostly not required with tablets.

The Long and Winding Road for Developing a Medicine 

When Contreras tells people about the work she does, they sometimes ask her why developing a medicine takes so long. On average, it can take about ten years for a medicine to make its way from the launch of exploring which molecules could be effective against a certain ailment until it lands on the shelves of a drug store, and only 8 percent of medicines make it through to regulatory approval.

“People often don’t know the complexity of the process— how long the process takes to get to the point where you can put a medicine on the market,” she says. “We need to generate the data to ensure that a drug is safe for patients, and that takes time.”