Understanding API crystallization process and its challenges

What is API Crystallization?

API crystallization refers to the process of transforming the active pharmaceutical ingredient (API) of a drug from a solution into a solid crystalline form. This is a crucial step in drug manufacturing because the crystalline form of an API can significantly influence its stability, solubility, uptake in the human/animal body and overall effectiveness. Crystallization also bridges the drug substance manufacturing and the drug product manufacturing towards its final application as a medicine. The process involves carefully controlling parameters such as temperature, solvent composition, and concentration to ensure the formation of crystals with desired properties (ex. crystals size, distribution).

Why crystallization is crucial
in drug product manufacturing?

Crystallization is crucial as the final step in drug product manufacturing because it directly affects the purity, stability, and reproducibility in production.

Purity and Consistency

Crystallization helps in purifying the active pharmaceutical ingredient (API) by removing impurities. It ensures that the drug substance is consistent in its chemical composition, which is essential for the safety and efficacy of the medication

Stability

Crystalline forms of APIs are generally more stable than their amorphous (non-crystalline) counterparts. A stable crystalline form ensures that the drug has a longer shelf life and maintains its therapeutic effectiveness over time. Also the selection of the most stable polymorphic state – when more than one crystalline structure exists for one single molecule – is important to reach the highest possible shelf life.

Reproducibility

Crystallization processes can be standardized to produce consistent batches of the API. This reproducibility is critical for ensuring that every dose of the drug performs the same way, which is a key requirement in pharmaceutical manufacturing.

Batch crystallized drug substances from solution

Crystallization in a large batch reactor in a manufacturing process is conducted in such a way that any variability in between two produced batches is reduced to an absolute minimum. In order to achieve this feature inside large tank sizes, the API is dissolved at elevated temperatures. While gently cooling, a preset quantity of solid API is added as very fine sized particles – called “seeds” – already having the features of the desired polymorphic form. During cooling, the API in solution will adhere to the crystalline seeds to generate grown crystals at the lowest possible temperature. To maximalize the efficiency of the process at the end usually an antisolvent is added to promote adhesion of the remaining API in solution to the crystals.

If this is executed in a very standardized way, the variability in between different produced batches is acceptable to be further treated downstream in the drug product manufacturing process steps.

What are the important parameters for the crystalline API in drug product manufacturing?

Once the crystalline API from the drug substance production is generated, during the drug product manufacturing, focus is set on the actual application of the API and its formulation. Other parameters come into play like the physical properties size and shape of the crystals, making a large part of the critical material attributes (CMA) of a drug product. Size, size distribution and shape of the crystals determine the actual drug application, dissolution and bioavailablity, dose uniformity, processability of the drug product:

Dissolution Rate and Bioavailability

The size of the crystals determines how quickly they dissolve in the body. Smaller crystals generally dissolve faster due to their larger surface area relative to their volume, which can improve the drug’s bioavailability—how effectively it is absorbed and used by the body. A uniform size distribution ensures that the dissolution rate is consistent, leading to predictable drug performance and therapeutic outcomes.

Dose Uniformity

In drug manufacturing, consistent crystal size and distribution help ensure that each dosage form (like a tablet or capsule) contains the same amount of active pharmaceutical ingredient (API). If the crystals vary widely in size, it can lead to uneven distribution of the API in the dosage form, resulting in variability in drug potency and potentially impacting patient safety.

Manufacturing Process Efficiency

Crystals with a narrow size distribution are easier to handle and process. They flow more uniformly through manufacturing equipment, mix evenly with excipients (inactive ingredients), and compress more consistently into tablets. This reduces the risk of production issues like segregation (where particles separate based on size), uneven tablet weights, or poor compaction, leading to more efficient and reliable manufacturing processes.

Product Stability

The size and distribution of crystals can affect the physical and chemical stability of the drug. For example, larger or irregularly shaped crystals might be more prone to breaking down or undergoing unwanted transformations, which could compromise the drug’s stability and shelf life. Consistent size and distribution help maintain the integrity and stability of the drug over time.

Control of Polymorphism

Crystallization conditions, including the size and distribution of crystals, can influence which polymorphic form of the API is produced. Different polymorphs can have different solubility, stability, and bioavailability. A controlled crystallization process that produces a uniform size distribution helps in consistently obtaining the desired polymorphic form, which is critical for maintaining drug efficacy and safety.

Challenges for batch produced crystalline API substances towards the change to drug product

While seeded batch crystallized APIs are in the correct polymorphic state and production is sufficiently consistent, the produced drug substance usually needs to be re-engineered towards its desired size and shape for its application. Hence, the addition of one or more additional process steps besides classic seeding, growing, filtration and drying are necessary: changes in shape and size are done with different grinding and milling techniques- wet or dry – followed by seeving steps to obtain the desired size and particle size distribution, avoiding a too large variability in between the smallest and largest crystals present in the drug product powder prior to final formulation.

Although applied consistently for nearly every produced API substance, any additional process step is very costly due to inherent losses of drug product for each different additional step. Also recycling of lost material during these steps comes at a high cost to work up this product to desired properties, if even possible.

Secoya Crystallization Technology’s unique proposition

At Secoya, we have developed a unique crystallization process that allows to reduce the total number of process steps to its bare minimum from drug substance to drug product. We bring the drug substance in solution, and we generate the final CMAs of the drug product in one single process step; followed by filtration and drying. No hustle anymore to generate correctly sized seeds, no more grinding, milling and sieving of the drug products. As a true benefit, our technology bridges completely the drug substance manufacturing with the drug production facility with the direct use of the manufactured API powder.

Discover the Secoya Crystallization Technology

Directly achieving the optimal crystal size for a solute in solution

Introduction

The development of a completely new technology does of course not come by itself. Many years on research on a specific molecule, Brivaracetam, has led to the creation of the understanding how to generate crystalline material while flowing heated solution through narrow capillaries. A large part of this research journey has been documented and published in Crystal Growth & Design, also a patent application WO2019215022A1 was submitted based on these results.

In general, our findings pointed out that solutes in solution can start to nucleate very rapidly inside reactors with reduced internal volume. More specifically, as Brivaracetam is a rather complex molecule to crystallize, we observed the possibility of selection a certain polymorphic form of Brivaracetam to nucleate preferentially. The benefits of these long, elongated reactors with narrow inner diameters and even smaller wall thickness are that the solutions are cooled down in a very controlled way from soluble conditions, through the metastable zone, and into the zone where spontaneous nucleation – whether homo- or heterogeneous – may take place. This cooling down is not affected by the fact that we use flow velocities inside these reactors from 10 to 100 cm/s; hence, the use of relevant flow rates – to obtain desired production rates of APIs – becomes possible. Together with the defined cooling of liquids flowing through our reactors, we have also observed to beneficial influence of occurring shear rate inside our reactors on the width of the metastable zone, resulting in a drastic increase in nucleation rates at identical conditions when increasing the shear rates inside the reactors. A side-effect was the observation of the absence of fouling during long-term productions of Brivaracetam from the start. On a side note, we have not considered fouling during the first years of research as we never encountered any blockages of the tubing, even during long runs. In the paragraph discussing fouling and blockages we will go deeper into the reasons behind the fact that blockages inside our reactors will only occur when several critical factors are or are not considered.

Developing a way to crystallize directly the correct crystal size for a solute in solution

From the start, our philosophy was based on the control of the number of nuclei appearing inside a crystallizing slurry. We had observed in literature several attempts to control crystal growth using difficult crystal growth models in different axes of a crystal, the use of CSTR tanks, etc. None of them we found satisfactory for this goal as it complexifies the process and you always rely on the use of solid seeds of some form and shape that results in a redundant process step if crystals are generated spontaneously. On the other hand, if one would be able to control how much nuclei are generated homogeneously while passing through a reactor, then in a simple, maybe even naïve, calculation, one would be able to predict their size once they have grown to their equilibrium state.

Suppose that you would have an initial solution concentration of 400 mg of solute per mL of solvent. And that at a low temperature solubility is 100 mg of solute per mL of solvent. That would mean that per mL of solvent you can crystallize – when performing for this example a cooling crystallization – 300 mg of crystals. Then, if you have 100 crystals in this slurry, or hundred thousand of crystals, this would then result immediately in completely different particle sizes once these crystals are fully grown.

 

 

Table 1: estimation of particle size of crystals as a function of the total amount of crystals present in a slurry for a given concentration and crystal density.
Mass to crystallize	300 mg
Density of a crystal	1 g/mL
	1 mg/µL
	1 mg/mm3
Number of crystals	volume / mm3	Spherical average length / µm	Cubic average length / µm
100	3	895	1442
1000	0,3	415	669
10000	0,03	193	311
100000	0,003	89	144
1000000	0,0003	42	67
10000000	0,00003	19	31

So, for an oral dosage form with average sizes preferentially below the 100 µm mark, anywhere between 10⁵ and 10⁶ crystals produced per mL solvent is to be achieved. Please note that in the above table we assumed both spherical and cubic particles leading to different expected crystal sizes. If we look at estimated nucleation rates for homogeneous crystallization at different conditions we will describe here below, in theory (Mersmann, Crystallization Technology Handbook, 2nd edition, ISBN 0-8247-05828-9, chapter nucleation) a nucleation rate can be expected in between 10¹² and 10²⁰ per cubic meter per second, which equals to 10⁶ and 10¹⁴ of crystals produced per mL. Comparing both values indicates that whenever we can reach nucleation conditions as set out in Figure 1 and control their evacuation out of the reactors to let the freshly generated nuclei grow in non-nucleating conditions, we would be able to separate nucleation and growth of crystals and target exact reproducible size whenever the passage through our reactors is as homogeneous as possible.

 

 

As stated in above figure, solubility and supersaturation are important parameters that rule the occurrence of nucleation. In fact, for a crystalline structure to appear, a treshold energy barrier needs to be overcome in order for the structured material to appear instead of molecules remaining disordered inside the solvent. The nucleation theory is of course already well described, but in general, for a molecule to start nucleating, this energy barrier is most easily depicted using the phase diagram of the solute in solution, as shown in Figure 2. This means that for a solute in solution, to the right of the solid line in Figure 2, needs to be cooled down in order to nucleate. The energy barrier is the most wide for primary homogeneous nucleation, which is nucleation from the solution without any other foreign material present. In the presence of foreign material – impurities, surfaces, etc. – but without any solute-own crystals, primary heterogeneous nucleation takes, with a lower energy barrier to be overcome as for homogeneous nucleation. Once crystals are present in the slurry, these may brake up due to fractures, shear effect, collisions, etc. These are grouped together as secondary nucleation – so with the presence of solute-own crystals in the slurry. Logically, these come at the lowest energy barrier to be overcome.

 

Following our philosophy to control the formation of crystals and to maintain the quantity of crystals nucleated, inside our reactors we aim for primary nucleation, whereas the gathering of the slurry coming out of the reactor has to be done in such a way that secondary nucleation is avoided.

To express this metastable zonewidth, at isothermal conditions supersaturation s is defined as the difference between the concentration C of a system and the solubility concentration at that temperature C*. To create a dimensionless number, this difference between C and C*, is divided by C*:

Once the metastable zonewidth is crossed for primary nucleation, the kinetics of nucleation – the number of nuclei generated – is increased by further cooling, generating a higher supersaturation value. As an example, in Figure 3 the difference in metastable zonewidth is shown between the compounds Brivaracetam and Aspirin in their proper solvents².

[1] Rimez at al. J Flow Chem 2020, 10, 241-249 (doi: 10.1007/s41981-019-00069-2)

The supersaturation value needed to obtain primary nucleation for Brivaracetam is of 0.6, and experiments can be conducted at concentrations as high as 400 mg/mL, resulting in very high supersaturation values and a large variability in crystal sizes while playing with different conditions can be obtained as published earlier (Rimez et al., Crystal Growth & design 2018, 18, 6431-6439 (doi: 10.1021/acs.cgd.8b00928)). For Aspirin, the metastable zonewidth when dissolved in water/ethanol is much larger, a supersaturation value of 5.7 needs to be overcome to observe nucleation in our reactors, making it for this example difficult to generate working conditions at supersaturations above the optimal value of Brivaracetam (σ = 6.7 instead of 4.6). However, both obtained supersaturations are high and it can indeed be expected that predicted nucleation rates and hence refined particles sizes can be obtained for both examples, with reported particle sizes between 50 and 200 µm for Brivaracetam³ and in used solvent between 400 and 800 µm for Aspirin². Hence, the key factor to crystallize directly the desired particle size is to nucleate a certain amount of nuclei inside the solution and gather this liquid to let the crystals grow to their equilibrium state, independent of the time required to do so, as long as primary nucleation event only take place inside the specific nucleation reactor. As a side-note: all solution passing through such a reactor needs to undergo the exact same cooling pattern as to homogenize maximally the nucleation rate for the complete production liquid envisaged.

The use of capillary reactors to control the nucleation rate while maintaining uniformity

In order to cool a liquid down not only very rapidly but also in a uniform way, we opted for millifluidic tubing with maximally 1 mm inner diameter. We conclude this after an experimental study on Aspirin (Rimez et az., J Flow Chem 2019, 9, 237-249 (doi : 10.1007/s41981-019-00042-z)) where we experimentally and by simulation demonstrated how a liquid cools down when it is injected at a constant rate inside a tubular reactor of 1 mm having a wall thickness of 150 µm and being placed in a water bath of at least 100 times the volume as opposed to the volume of the reactor. For the study on Aspirin, we used a reactor of 3 m length which corresponds roughly to 3 mL of volume; this reactor was placed inside a 1 L water bath that was set at the desired temperature. Then we measured using thermocouples at different distances the temperature inside the reactor while liquid was flowing through the reactor. This liquid was preheated at the desired solution temperature for the Aspirin solution in ethanol/water (50/50 v/v). this overlapped with the simulate values for the tube center temperature. In the next figure, we show the simulated values for both the tube center and the simulated temperature at the tube wall.

In Figure 4 the liquid entering the reactor is indicated at distance zero. The temperature of the liquid drops drastically at the tube wall (dashed black lines), followed by the temperature in the center (solid black line). The dots in orange indicate when the liquid passes the solubility temperature of the concentration of 200 mg/mL; the blue dots correspond to the metastable zonewidth. It can therefore be observed that after a distance shorter than 50 cm inside the tubing the solution is already in conditions where spontaneous nucleation will take place, the remainder of the time inside the tubing, 4.7 s in total at ruling flow velocities, renders the possibility to produce a large quantity of nuclei in order to reach the desired amount of crystals. These short residence times prevent crystals to grow to sizes that might become difficult to handle.

Any crystal growth is therefore also conducted outside of our reactors. In general, the next schematics represent very well how we perform crystallizations, see Figure 5: a heated liquid is injected at a constant rate inside a tubular reactor sitting at a low temperature at which the nucleation should take place. Before this cooling sown there is a possibility to alter flow hydrodynamics inside the tubing or add an antisolvent – these topics will be discussed later. While flowing through the tubing all liquid is always cooled down in exactly the same way: laminar flow conditions are reached for the combination of flow rates and tubing diameter we apply, therefore plug flow conditions are reached and all material is constantly moved forward through the tubing. Inside the phase diagram we go as fast as possible to the desired nucleation temperature (horizontal arrow from high to low temperatures in the phase diagram). At this point, the nucleation is already started, indicating a drop in solute concentration (vertical arrow in the phase diagram) while the liquid is still flowing throught the tubing. Then, at the end of the tubing, the slurry containing fast growing crystals can be gathered inside a waiting tank for the crystal growth to be fulfilled or, when the growth kinetics allow this, directly on a filtration unit. For crystal growth conditions, any temperature might be selected.

 

Benefits of capillaries: solid particle mobility and shear rates

The uniformity in the cooling of liquids flowing through the tubing but also the development of a laminar flow regime inside the capillaries is beneficial for SCT. As the estimated Reynolds numbers are well below 4000, see Table 2, generally considered the threshold for turbulent flow, laminar flow behavior is to be expected. On the other hand, capillary reactors possess other beneficial aspects that are in use inside our reactors.

Table 2: typical flow rates with corresponding flow velocity inside capillary reactors and estimated Reynolds number using water at room temperature as basis for calculation.
Flow rate	mL/min	10	20	30
Flow velocity	cm/s	21,2	42,4	63,7
Reynolds number		20	400	600
Shear rate	s-1	1698	3395	5093

At usual flow rates inside the reactors, shear rates at the tube are above 1000 s^-1. For other types of solid particles flowing through narrow channels under laminar flow conditions and elevated shear rates, it is known that these particles do not migrate towards the channel wall. Most famously is the Fåhræus–Lindqvist effect that describes the migration of erythrocytes to the center of the vessel, leaving only plasma neat the wall of the vessel (https://en.wikipedia.org/wiki/F%C3%A5hr%C3%A6us%E2%80%93Lindqvist_effect). In Figure 6 an artificial vein is shown with hemoglobin flowing through, showcasing the absence of hemoglobine at the tube wall.

 

When simulating the preferential position of solid particles inside circular tubings under constant flow conditions, Javier Rivero-Rodriguez and Prof. Benoit Scheid of the Université libre de Bruxelles (Rivero-Rodriguez and Scheid, J Fluid Mech 2018, 842, 215-247 (doi: 10.1017/jfm.2018.78)) discovered that small particles, when not subjected to gravity, will migrate under laminar flow conditions to a preferentially eccentric position, away from the tube center. At the tube wall the lowest probability to retrieve a solid particle is observed. This preferential position is shown in Figure 7. It is demonstrated that the difference in flow velocity in the laminar flow regime pushes the particle away from the tube center. On the other hand, the particles bounce off the tube wall, generating an equilibrium position off center. Therefore, as long as the particles are not subjected to gravity, the flow conditions inside of the reactors prevent collisions and deposition on the tube wall, resulting on blockages of the tubing.

Using Secoya’s Crystallization Technology, a large amount of nuclei are however formed at different conditions, which may provoke coagulation of these particles, very fast crystal growth, etc. Therefore, the use of a certain length for the reactor depends on the trade-off between sufficiently high nucleation rates and avoiding the possibility to block the tubing during operation due to too intense growth for example. The study to find the optimal reactor dimensions is an integral part of the development cycle of the process at the laboratory scale.

Another benefit of the tubular reactors is the high shear rates obtained inside. Mura and Zaccone have described mathematically the preferential nucleation conditions for particles under flow conditions and high shear rates (Mura and Zaccone, Phys Rev E 2016, 93, 042803 (doi: 10.1103/physRevE.93.042803)). in a joint study between Zaccone, ULB and Secoya, experimental data further evidenced this beneficial effect of shear rate in flow on the nucleation rate of a solute in solution (Debuysschère et al., Cryst Growth Des. 2023, 23, 4979-4989). In this work a cooling crystallization of Glycine in water was conducted. All Thermodynamic variables were kept constant (solution concentration and temperature, residence time at low temperature, nucleation temperature, etc.). The only variable was a change in shear rate while flowing through the reactor. This was achieved by varying the capillary diameter, flow rate and reactor lengths to obtain always the same thermodynamic conditions. The result was that the measured nucleation rate, shown in Figure 8a goes through an optimal value at a shear rate of 3000 s^-1 and Reynolds number of 340 for 98% pure Glycine, whereas 99.5+ % pure Glycine had its maximum at a slightly lower shear rate of 1700 s^-1. Other evidences on the influence of more localized shear rates generated inside the tubing in different studies (different studies already referenced here above)  lead to further evidencing the large impact of shear rates on the nucleation rate of a solute in solution while cooling down. For any cooling crystallization study, the shear rate influence is part of the development cycle for optimization of the crystallization of any molecule.

Conclusions

Secoya’s Crystallization Technology is based on the adaptation of the size and shape of tubular reactors to the speed of nucleation of solutes in solution. The overall short residence times and uniform cooling conditions inside the reactors result in the control of primary nucleation, enabling a prediction of the final particle size of crystalline material after complete growth of the crystals, outside the reactor in a collecting vessel. Focusing only on nucleation in flow conditions also avoids blockages during production, as nuclei inside the reactors will not be able to migrate to the tube wall resulting in blocked tubings. The high shear rates obtained inside the reactors have an extra beneficial effect on the nucleation rate.

Join Secoya Technologies at CPHI Milan from October 8th to 10th.

WEBINAR: Transforming your crystallization process (Recording available)

Screening crystallization parameters for targeted particle size distribution might be challenging and time-consuming.

Join this webinar to discover how Secoya’s Crystallization Technology transforms the process with spontaneous nucleation, making it faster and more efficient. During this LIVE session, the setup of the instrument will be shown for both cooling and antisolvent crystallization. At the end of this webinar, Bart Rimez our technology lead will explain the overall philosophy of Secoya.

Book your seat and learn how the SCT technology can be extrapolated to other molecules, how to obtain the required particle size distribution with the setup of experimental designs and how to upscale it using the SCT-PILOT unit.

Speakers

Bart Rimez, Secoya Co-Founder and Crystallization Tech Leader

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PUBLICATION: Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations

Nandi, S. et al. Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations. Pharmaceutics 2024, 16, 376. https://doi.org/10.3390/pharmaceutics16030376

Abstract

A bottom-up approach was investigated to produce long-acting injectable (LAI) suspension-based formulations to overcome specific limitations of top-down manufacturing methods by tailoring drug characteristics while making the methods more sustainable and cost-efficient. A Secoya microfluidic crystallization technology-based continuous liquid antisolvent crystallization (SCT-CLASC) process was optimized and afterwards compared to an earlier developed microchannel reactor-based continuous liquid antisolvent crystallization (MCR-CLASC) setup, using itraconazole (ITZ) as the model drug. After operating parameter optimization and downstream processing (i.e., concentrating the suspensions), stable micro suspensions were generated with a final solid loading of 300 mg ITZ/g suspension. The optimized post-precipitation feed suspension consisted of 40 mg ITZ/g suspension with a drug-to-excipient ratio of 53:1. Compared to the MCR-CLASC setup, where the post-precipitation feed suspensions contained 10 mg ITZ/g suspension and had a drug-to-excipient ratio of 2:1, a higher drug concentration and lower excipient use were successfully achieved to produce LAI microsuspensions using the SCT-CLASC setup. To ensure stability during drug crystallization and storage, the suspensions’ quality was monitored for particle size distribution (PSD), solid-state form, and particle morphology. The PSD of the ITZ crystals in suspension was maintained within the target range of 1–10  m, while the crystals displayed an elongated plate-shaped morphology and the solid state was confirmed to be form I, which is the most thermodynamically stable form of ITZ. In conclusion, this work lays the foundation for the SCT-CLASC process as an energy-efficient, robust, and reproducible bottom-up approach for the manufacture of LAI microsuspensions using ITZ at an industrial scale.

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WEBINAR: Case study – Single crystal formation in core-shell microcapsules

This webinar introduces the latest advances in core-shell microcapsule technology. Discover how microcapsules are used as a versatile tool in drug delivery, encapsulation, crystallization, compound characterization, and more.

Explore the challenges of traditional microencapsulation methods and the transformative potential of microfluidic technology in producing precise, uniform microcapsules. Gain insights into the advantages of UV light crosslinking for rapid and solvent-free capsule production (Methacrylate-based resins, PEGDA, PEGDMA).

In the case study discussion of the program, a particular emphasis will be placed on the use of microcapsules for the screening of crystallization conditions.

Learn how to generate hundreds of identical UV-crosslinked microcapsules per second, produced by Secoya Technologies’ RayDrop and its all-in-one platform.

Speakers

Joseph Farah : Microfluidic Application Engineer·

Marie Mettler : R&D Engineer – Secoya Technologies

Adrien Dewandre : Technology Lead – Emulsification & Droplet generation – Secoya Technologies

Meet us at the Flow Chemistry Pavilion at ACHEMA 2024, 10 – 14 June 2024 Frankfurt am Main (hall 8 booth E64-020)

Join us for the 3rd edition of the Flow Chemistry Pavilion at ACHEMA 2024!

The Flow Chemistry Pavilion brings together 25+ Companies working in the area of Flow Chemistry & gives visitors the opportunity to meet the Flow Community at a Global Tradeshow. Alongside the five-day exhibition will be a two-day Symposium, enabling visitors to learn what’s new in the area of Continuous Manufacturing.

Where to find us: hall 8 booth E64-020.

Secoya at Formulation & Delivery to present Crystallization and Encapsulation technologies

Secoya Technologies has confirmed its participation in the upcoming Formulation and Delivery Congress set to be held in London from April 26th to April 28th.

Meet Diala Youssevitch, Adrien Dewandre and Bart Rimez to discover our latest API encapsulation and crystallization improvements.

About Formulation and Delivery

Formulation & Delivery 2024 aims to connect pharmaceutical & biotech representatives as well as academia for high-level discussions on the latest innovations in pharmaceutical drugs formulation, drug delivery, inhaled therapeutics & RNA development.

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ACS publication: Parameter Optimization from Laboratory- to Kilogram Pilot-Scale Operations in Crystallization

Secoya at Bio Fit Event (Marseille)

CRYSTA’DAYS – Two-day Crystallization dedicated event hosted by Secoya Technologies

In November 2023, a two-day event orchestrated by Secoya gathered a community of experts in crystallization in Louvain-La-Neuve. During these two dedicated days technology leads, esteemed researchers and academics showcased their groundbreaking work captivating an audience of industry experts coming from all around Europe.

 

Title	Speaker
From microfluidics at TIPs to Secoya	Prof. Benoit Scheid (ULB)
Introduction to Secoya crystallization technologies and crystallization	Dr. Bart Rimez
The theoretical and mathematical description of nucleation in shear flow conditions	Prof. Alessio Zaccone
The nucleation of molecules in solution using shear flow	Robin Debuysschère
API crystallization with Secoya Technology	Erik ter Voert
Introduction to the new SCT-LAB instrument	Dr. Bart Rimez
Filtration by DrM, Dr. Müller AG	Patrick Morsch
High throughput single crystal formation in core-shell capsules	Marie Mettler
From lab to pilot to scale-up ICE version: translation of conditions + case studies	Bart Rimez

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BACTERIA AND YEAST ENCAPSULATION METHOD IN SMALL DOUBLE EMULSIONS

Abstract

The precise manipulation, quick cultivation, and delicate detection of yeast and bacteria are crucial in microbiology and biomedicine for behavior monitoring, identification of phenotypes, physiological assessment, and molecular analysis.

Microfluidic droplets have proven to be an effective method for encapsulating yeast and bacteria in highly monodisperse droplets for high-throughput screening and analysis of their phenotypes, subcellular structures, genes, and metabolites.This application note details the encapsulation of the yeast strain S. cerevisiae CEN.PK 113-7D and the bacterial strain L. cremorsi MG1363_GFP in double emulsions of 42 µm size using the Cell Encapsulation Platform, resulting in Microencapsulation of Bacteria and Yeast.

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Single crystal formation in core-shell capsules (ChemComm Oct.23)

BREAKING NEWS: Secoya Technologies and ULB achieved a patent milestone in India.

 This momentous achievement allows Secoya Technologies to explore and expand into new markets.

NEW Application Note: A quick and efficient double emulsion generation method for flow cytometry droplet sorting

WEBINAR: Upscaling of the crystallization process towards a full continuous crystal production

About this Webinar:

During this webinar, Bart Rimez our expert in Crystallization, demonstrated how the Secoya Crystallization Technology (SCT) process can be seamlessly scaled up from laboratory to production scale by tightly controlling various parameters.

At the laboratory scale, a set of parameters is identified and enables the production of the desired particle sizes and distributions. This same set of parameters can then be directly transferred to pilot-scale or production-scale processes, thus providing a reliable and efficient means of scaling up the SCT process.

Speakers:

 

Bart Rimez, PhD | Co-owner And Technology Lead at Secoya Technologies
Diala Youssevitch | Technical Sales Manager

Invited speaker: Jan Vogeleer | Managing Director, Fette Compacting

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NEW White paper: The upscaling of lactose crystallization towards a full continuous crystal production

Secoya will be attending Formulation & Delivery 2023 (25 – 26 May) | London, UK to present Crystallization Technology

New White paper: 5 USE CASES OF CONTROLLED DOUBLE EMULSIFICATION PROCESS FOR ENCAPSULATION

Secoya Technologies raised €1M to commercialize its next-gen microfluidic equipment

We are delighted to announce the completion of our fundraising for an amount of €1million.

Bertrand Loriers, CEO commented: “This is a new milestone for Secoya. It will allow us to move to a new level of growth while we have a better knowledge of our customers and potential markets. These resources will indeed be allocated in a relevant way to our commercial deployment and to the operational reinforcement required to support our development. We seize the opportunity to thank our shareholders for trusting us.”

With a board of industry veterans, including former Delphi Genetics CEO Cédric Szpirer, Univercells co-founder Jose Castillo, Jean-Marie Solvay, and Stéphanie Hoffmann-Gendebien, Secoya already counts several major pharma companies among its clients in Europe and is expanding to the US.

Read the full article (in French): https://www.lecho.be/entreprises/pharma-biotechnologie/secoya-revisite-les-procedes-de-production-en-biopharma/10448380.html

Secoya Technologies announces the coming release of the InstaDrop

All the team is thrilled to announce in the coming weeks the release of the 𝗜𝗻𝘀𝘁𝗮𝗗𝗥𝗢𝗣, the most versatile instrument to set up precise, repeatable and cost-effective API encapsulation processes.

Broadly used in the pharmaceutical industry, encapsulation of active ingredients in microparticles allows to improve their delivery and absorption. Nevertheless, not all solutions guarantee a high control of the particle size Aand a robust long-run production process.

By its conception, the 𝗜𝗻𝘀𝘁𝗮𝗗𝗥𝗢𝗣 allows the easy control of flow and particle size. And as it includes our 𝗥𝗮𝘆𝗱𝗿𝗼𝗽® technology, the 𝗜𝗻𝘀𝘁𝗮𝗗𝗥𝗢𝗣 is perfectly suited for bead and capsule microencapsulation, preformulation screening and small batch production.

WEBINAR: Double emulsion production compatible with FACS for cell sorting application

Meet Secoya’s team at CESPE conference, September 15th!

Secoya Technologies exclusive presentation at the CGOM14 conference

WEBINAR: SCT-LAB laboratory setup (LIVE DEMO), the first step to optimize your crystallization process

Secoya at CPhI WW, November 9-11, 2021

Secoya Technologies will participate at the next CPhI Summit in Milan from November 9 to 11, 2021. If you want to discover more about our technologies or see our products in real life, come and meet us at out booth 10K90 (Pavillon PMEC)!
If you would like to meet with one of our technology experts on site, do not hesitate to contact us at info@secoya.com.

Looking forward to meeting you!

Secoya celebrates its 2nd anniversary!

The SCT approach to crystallization

Secoya at CPhi discover 17-18 May 2021

Would you like to learn more about our innovative technologies? Join us at the CPhi Discover and come to our virtual booth for a discussion.

Sign up for free

Secoya at CCP Summit 23-25 March 2021

20/01/2021

Secoya Technologies will participate in the next CCP Summit from March 23 to 25, 2021.  Bart Rimez, co-founder and Technology Lead, will give a presentation on the Secoya Crystallization technology.

Publication on Raydrop

Adrien Dewandre and Youen Vitry, Technology leads at Secoya, and Benoit Scheid, Chairman of the Board of Secoya and Maître de Recherche FNRS at ULB, were involved in an experimental and numerical study of the Secoya droplet generator, the Raydrop. Their work on “Microfluidic droplet generation in a non-embedded co-flow-focusing using 3D printed nozzle” is published in the journal Scientific Reports.

Secoya-Fluigent Webinar on double emulsion

28/10/2020

On November 17rd at 5 pm, Youen Vitry, co-founder and Encapsulation Technology Lead, will give a Webinar in collaboration with Fluigent on the Raydrop technology for the generation of double emulsion.

Register to the webinar : https://www.fluigent.com/resources/webinars/

Secoya-Fluigent Webinar on the Raydrop technology – Replay

28/10/2020

On June 23rd, Adrien Dewandre, co-founder and Encapsulation Technology Lead, has given a Webinar in collaboration with Fluigent on the Raydrop technology for the droplet generation.

Access now to the replay : https://webikeo.com/webinar/raydrop-a-universal-droplet-generator-based-on-a-non-embedded-co-flow-focusing/replay

Secoya at CPHi Festival of pharma 5-16 October 2020

26/08/2020

Secoya Technologies will participate in the next CPHi Festival of Pharma from October 5 to 16, 2020.  If you would like to know more about one of our technologies, do not hesitate to request a virtual meeting through the CPhI platform. 

Publication of complex systems modeling

26/08/2020

Jean Septavaux, Technology lead at Secoya has been involved in the modelling of complex molecular systems with the CSAp lab from the University of Lyon. Their work on “The dark side of disulfide-based dynamic combinatorial chemistry” was published in the journal Chemical Science. 

Secoya at Virtual Process Show 8-11 September 2020

26/08/2020

Please find below the timeslots and links to which the Secoya webinar on our crystallization technology will be broadcasted at the Virtual Process Show.

The webinar describes in detail the principles and the unique benefits of this new crystallization technology. It includes also the presentation of the latest results on the technology.

11.09.2020 at 10:00 CET
11.09.2020 at 18:00 CET
12.09.2020 at 02:00 CET

Would you be interested in this new technology ? Please join us at one of the three webinar time slots.

Secoya signs a collaboration contract with a top 5 pharma

03/06/2020

We are pleased to announce that Secoya Technologies has signed an important collaboration contract with a world top 5 pharmaceutical company. The collaboration focuses on the joint use of intensified chemical synthesis and pervaporation technologies developed by Secoya and aims to develop a prototype that fits into the client’s production process.

Hydrodynamics matters to control the crystallization of API

3/02/2020

Dr. Bart Rimez, co-founder and Crystallization Technology Lead, was invited to publish in the Emerging Scientists issue of Journal of Flow Chemistry, coming out beginning 2020. The paper deals with our findings on the synergistic effect of nucleation thermodynamics and hydrodynamics to increase nucleation rate. Read more

Secoya at Flow Chemistry Europe 2020

29/01/2020

Dr Rimez, co-founder and Crystallisation Technology Lead, will be present at the forthcoming conference, Flow Chemistry Europe 2020, 3-4 March 2020, Cambridge (UK). Dr Rimez will give a lecture on the development of capillary crystallisation reactors.

Worldwide distribution of the droplet generator RayDrop by Fluigent

28/01/2020

On 28^Th January 2020, Fluigent and Secoya Technologies signed an exclusive distribution agreement under which Fluigent is responsible for the marketing and the sales of the RayDrop®, an innovative technology of Secoya dedicated to the production of droplets or particles for multiple applications. More information on the RayDrop on www.fluigent.com.

Intensification for sustainability

13/01/2020

Would it be possible to valorise a waste stream… by purifying another ? Dr. Jean Septavaux, co-founder of Secoya Technologies, co-authored a paper in Nature Chemistry describing a methodology for the convergent purification of electronic and gas waste streams.  By using the unique properties of polyamines solutions upon capture of CO₂ from car exhaust fumes, the authors manage to separate with a high selectivity the valuables metals contained in a dissolved car battery electrode.

 Read the article