Versatile equipment driving drug discovery


How drug developers can conduct more experiments with less material

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 that 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, approximately $1.42 trillion was spent on medicines in 2021, up from $887 billion in 2010. This is set to increase to nearly $1.8 trillion by 2026, fuelled 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 that patients are receiving their medications, guaranteeing them the best possible care, it’s crucial that laboratories adopt a “doing more, with less” approach to crystallisation. 

Crystallisation chemistry in drug formulation
For drug formulation, crystallisation 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 crystallisation, polymorph and solubility screens. 

This includes crystallisation by evaporation and cooling. The choice of crystallisation method depends on the specific behaviour 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 analyses with a very small amount of material.

At a time when conserving research material is vital, pharmaceutical companies find themselves struggling to do the multitude of experiments required to produce good quality APIs. This is when versatile analytical equipment, such as Technobis’ CrystalBreeder, is making a difference to laboratories globally. 

By using the CrystalBreeder, scientists can perform enough crystallisation 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 0.06–0.10 mL. This is crucial because the more information laboratories can gather from this small amount, the quicker they can deliver drugs to market.

More experiments with less material
The CrystalBreeder is designed to work with much smaller operating volumes, compared with traditional solutions. Previously, up to 1 g of API was required to conduct a full crystallisation screen — compared with 100 mg with the CrystalBreeder.

This means that laboratories can run more advanced experiments using the same amount of material or, in cases when 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 crystallisation, laboratories can benefit from single benchtop instruments that do slurry experiments, thermocycling, vapour diffusion and sublimation with as little as 1 mg 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 into the blood to reach its site of action. Instead, it is digested in the gastrointestinal tract. Therefore, altering the physicochemical properties with particle engineering must take place as early as possible during the discovery phase.

The CrystalBreeder, with additional modules for vapour diffusion and evaporation crystallisation, can easily perform controlled crystallisation 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 multireactor, giving laboratory staff control of 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.

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As pressure mounts for pharmaceutical companies to deliver medicines using fewer resources in short timeframes, perhaps it’s time to take advantage of versatile analytical equipment. This doesn’t have to involve an expensive overhaul of your entire laboratory, just the cost-effective investment in automated benchtop instrumentation that will allow you to conduct more advanced experiments with small amounts of material.