Versatile equipment driving drug discovery

Demand for innovative pharmaceutical products is growing because of the need to treat an ageing population with increasingly complex conditions. However, ongoing supply chain disruptions mean drug developers may only have access to small amounts of compound to work with, limiting the work they can do. Here Dr Carmen Guguta, global head of business development and marketing at solid-state research technology provider Technobis Crystallization Systems, explores how drug developers can conduct more advanced experiments with small amounts of material using versatile analytical equipment.

According to Statista, in 2021, approximately $1.42 trillion was spent on medicines globally, up from $887 billion in 2010. This is set to increase to nearly $1.8 trillion by 2026, fueled by an ageing population and the need for new drugs to treat rare and specialty diseases.

However, pharmaceutical companies are still finding it difficult to access active pharmaceutical ingredients (APIs) because of supply disruptions escalated by the pandemic and the war in Ukraine. To ensure patients are receiving their medications, guaranteeing them the best possible care, it’s crucial that laboratories adopt a ‘doing more, with less’ approach to crystallization.

Crystallization chemistry in drug formulation

For drug formulation, crystallization is an effective way of producing APIs with a specially designed set of physical, structural, and chemical characteristics that give the best overall drug performance. To achieve this, laboratory staff must undertake several crystallization, polymorph, and solubility screens.

This includes crystallization by evaporation and cooling. The choice of crystallization method depends on the specific behavior of the compound involved and product characteristics required. However, the main issue in early drug development is the availability of the API itself.

The amounts of API a synthetic chemist can produce is no more than 500 milligrams. Therefore, in the next stage of drug development, scientists face the challenge of performing multiple experiments and analysis with a very small amount of material. At a time when conserving research material is vital, pharmaceutical companies find themselves struggling to carry out the multitude of experiments required to produce good quality APIs. This is where versatile analytical equipment, like Technobis’ CrystalBreeder®, is making a difference to laboratories globally.

By using the CrystalBreeder®, scientists can perform enough crystallization experiments and still have enough material for solubility and pharmacokinetic analyses. For example, they can conduct up to 32 parallel experiments at working volumes of 0.06 – 0.1 milliliters. This is crucial because the more information laboratories can gather from this small amount, the quicker they can deliver drugs to the market.

More experiments with less material

The CrystalBreeder® is designed to work with much smaller operating volumes, compared to traditional solutions. Previously, up to one gram of API was required to conduct a full crystallization screen compared to 100 milligrams with the CrystalBreeder®. This means laboratories can run more advanced experiments using the same amount of material or, in cases where samples are limited, they can gather as much data as before while preserving a lot more of their sample.

For example, in addition to cooling and evaporation crystallization, laboratories can benefit from single benchtop instruments that carry out slurry experiments, thermocycling, vapor diffusion, and sublimation with as little as one milligram of material. These are more advanced processes that involve carefully controlling vacuum pressures, temperatures, and overhead stirring speeds to obtain X-ray quality single crystals for structural determination of the API.

Solubility data is crucial for decision-making in the early stages of drug development. For example, if a drug intended to be administered orally isn’t sufficiently soluble, it may not be absorbed in the blood to reach its site of action. Instead, it is digested in the gastrointestinal tract. Therefore, altering the physicochemical properties in particle engineering must take place as early as possible during the discovery phase.

The CrystalBreeder®, with additional modules for vapor diffusion and evaporation crystallization can easily perform controlled crystallization screens, growing single crystals within a few days. Technobis’ customers have previously reported that the traditional methods can take weeks. Therefore, as well as being versatile, the CrystalBreeder® will reduce the time needed for drugs to get onto the market.

Versatility is key

The CrystalBreeder® is a compact multi-reactor, giving laboratory staff control over the temperature, sampling rates, and stirring speeds for eight disposable block reactors using an automated computer software. For ease of use, staff can set predefined temperature profiles, vacuum pressures, and stirring speeds using the software, for repeatability and control. Furthermore, the shape of the reactor’s vials mimics that of traditional NMR tubes, which are ideal vessels for growing crystals.

As pressures mount for pharmaceutical companies to deliver medicines using fewer resources in short timeframes, perhaps its time to take advantage of versatile analytical equipment. This doesn’t have to involve an expensive overhaul of your entire laboratory, but simply investment in automated benchtop instrumentation that will allow them to conduct more advanced experiments with small amounts of material.

To find out more about Technobis Crystallization Systems and its benchtop products, including the Crystal16®, CrystalBreeder®, and Crystalline®, head to the website today.