As experts in first-time-in-human formulations, for years the scientists at Metrics Contract Services have successfully applied the Xcelodose® encapsulation technology to place Active Pharmaceutical Ingredient (API) directly into capsules with high precision and accuracy over a wide range of dosages.
Now, they have advanced their expertise in micro-dose formulations by executing multiple programs with Phase I clinical trial materials requiring less than 1 milligram (mg) of API per dose.
The stated accuracy limit of the Xcelodose® — based on its pepper pot filling technology and taring every capsule prior to filling — generally lies around 1 mg.
By comparison, the average weight of one grain of long-grain rice is 29 mg.
Brad Gold, PhD, vice president of pharmaceutical development, said placing such micro-doses of API directly into capsules requires a combination of scientific and engineering skills.
“It’s a real challenge to measure such low doses accurately into capsules each and every time, which is of paramount importance to ensure safe and reproducible clinical studies that are scientifically sound,” he said.
The Xcelodose® encapsulator relies in large part on gravity to help move API into capsule, a process that readily works when scientists are working with API amounts of 10 mg or more.
The design of the filler head — both in size and in number of holes — must be developed for each API. Moreover, and just as importantly, a high throughput device is carefully set up to achieve the critical level inside the Xcelodose® hopper. This set up is unique for each API and is based on its particle size, shape, and electrostatic charge.
However, when a dose of API weighs substantially less than a grain of rice, the process generally becomes one of strategic placement rather than flow and measurement.
“It can be a slow process,” Gold said. “But that’s how it is when you’re working with next to nothing in terms of weight and size.”
Gold credits his colleague, Andrew Green, associate scientist in Metrics Contract Services Pharmaceutical Development group, for developing niche talent for micro-dosing API into capsules.
And although the work can be exacting, Green said the benefits to micro-dosing are well worth the effort.
“We don’t have to use as much API, and that saves money, work and time for clients,” he said. “And we have a very low rejection rate when developing micro-doses for clinical trial materials, which is another way we conserve API. So it spares API and it moves a promising new therapeutic treatment into clinical trials more quickly.”