Five essential steps in the drug discovery and development process

You know I think my blog is great, but I can appreciate when my colleagues also put out some good material. Here, I draw inspiration from a food analytics blog to instead describe a typical process for R&D extraction & synthesis labs: drug discovery and development. Read on to see the common steps for this type of workflow and tips on how to optimize each part of the process.

I don’t know if you’ve already heard the news, but my colleagues at BUCHI recently launched a food analytics blog, “Shallot Holmes & The Food Detectives”. The blog has really interesting scientific content with five food detectives, Shallot Holmes, Eggcule Poirrot, Miss Mapple, Nancy Beef, and Lieutenant Cornlumbo solving challenges in fat extraction, protein determination with the Kjeldahl method and NIR analysis of foodstuffs.

Well, one of the posts I read was on using the NIR technique to measure raw ingredients, intermediates, and final products during coffee processing. I was really curious to find out more about the entire workflow that converts coffee beans to coffee powder.

And just like this, I was inspired into writing you a similar post. The one main difference, rather than a food production process, I could cover the typical drug discovery and development process!

I mean, our blog also focuses on nearly all the techniques needed to analyze compounds for potential therapeutic effects. Let me summarize the overall process for you. During drug discovery, ingredients of interest are extracted from natural sources or synthesized in the lab. The potential candidates are then analyzed for desirable characteristics and function.

Any drug discovery workflow typically requires reliable, high-throughput methods, so you can quickly and accurately identify promising compounds.

Once an active pharmaceutical ingredient (API) has been identified, the drug development and production process can begin.

During drug development, emphasis is placed on process optimization and efficient quality control to prevent expensive mistakes on a large-scale level.

Let us now explore the five steps that are typical to the drug discovery and development process.

1. Extraction/ Synthesis – Reflux synthesis and Soxhlet extraction are the most used techniques for preparation of a sample. The Soxhlet extraction method, for example, applies the principles of reflux and siphoning to continuously extract the target of interest with fresh solvent. The method is highly automated, which helps you achieve higher product yields in less time. Reflux synthesis and Soxhlet extraction can be performed with a rotary evaporator equipped with relevant accessories. This gives you the benefit of performing both techniques with one instrument.

When scaling up for drug development applications, try to keep the same parameters from your Reflux synthesis or Soxhlet extraction steps. To help you achieve this, consider using equipment that is compatible with both smaller flask sizes and industrial-sized labware. An industrial evaporator can be used to scale up synthesis or extraction of target compounds.

2. Concentration – After you have synthesized or extracted your compound, you must concentrate or dry your mixture by evaporation. I’ve got some time-saving tips for you here. Consider using parallel evaporation to dry multiple samples simultaneously or a Dewar accessory to help prepare your sample for freeze drying directly on your rotary evaporator.

3 – Separation/purification – Now that you have reached the purification stage, I would suggest using flash chromatography as a quick pre-purification step, to separate the compounds from the concentrated mixture. I would then follow-up with prep HPLC to reach higher purity of the target compound. I would also recommend using systems with both UV detector and ELS detectors to ensure you don’t miss your target of interest.

To simplify your drug development process, consider using systems with different sizes of flash cartridges, prep HPLC columns, glass columns, as well as collection vessels. Here, it might also be beneficial to have different options for sample loading, including the possibility to load both solid sample via a solid loader and liquid samples via syringe, loop or an external pump.

4 – Concentration by freeze drying – After the separation, you need to concentrate your pharmaceutical compound of interest yet again. By using a gentle process, such as freeze drying, you can remove solvents with minimal damage to sensitive products. The technique uses stable parameters which also improves the reproducibility of your drug discovery and development process.

5 – Determination of purity – The last step in drug discovery, similarly to analysis of the final chocolate products, involves stringent quality control. One way to analyze the purity of your compound is to determine the melting point of your target compound. Some melting point systems are even compliant to Pharmacopoeia.

As a sign-off tip, during the development process, it could be challenging to incorporate your compound into a formulation without losing properties or displaying unwanted characteristics. One way to optimize your formulation is to try pre-formulation via spray drying or encapsulation. These techniques result in dry particles, microcapsules, wet beads and core shell capsules from various materials and could help improve the properties of your final formulation.

Nearly the same steps are needed to also analyze novel chemicals of interest for their exciting properties. This is a classic case of two birds with one stone, one workflow both for drug and for chemical novel compound discovery!

This topic, no wonder, is rather expansive and I have barely touched upon it here. If you are interested in finding out more information, watch a free webinar on the “Five key steps in drug discovery” or download an infographic with tips on the discovery and development of novel compounds.

So, which one of us did a better job at describing a complete workflow, myself or Lieutenant Cornlumbo with his coffee production process? Leave me your vote in the comments section below!

Till next time,

The Signature of Bart Denoulet at Bart's Blog