Luc Aerts

Union Chimique Belge (UCB) | UCB

The physicochemical properties of molecular crystals, such as solubility, stability, compactability, melting behaviour and bioavailability, depend on their crystal form¹. In silico crystal form selection has recently come much closer to realization because of the development of accurate and affordable free-energy calculations2–4. Here we redefine t...

In the original version of this Article, there was an error in the address for affiliation 4. This has now been corrected in both the PDF and HTML versions of the Article.

The active pharmaceutical ingredient rotigotine—a dopamine agonist for the treatment of Parkinson’s and restless leg diseases—was known to exist in only one polymorphic form since 1985. In 2008, the appearance of a thermodynamically more stable and significantly less soluble polymorph led to a massive batch recall followed by economic and public he...

It is well known in industrial applications involving powders and granular materials that the presence of electrostatic charges influences drastically the material flowing properties. The triboelectric charges are produced during flow at the contacts between the grains and at the contacts between the grains and the container. Unfortunately, the tri...

The relevance of co‐crystals for pharmaceutical development is demonstrated by the constant growth of the number of papers and patents published in the two last decades. Co‐crystallization appears to be an efficient means to modulate the solid state properties of a pharmaceutical active ingredient (API) within the crystalline state. It is also a cr...

This article highlights the unusual behavior of Brivaracetam (BRV: an active pharmaceutical ingredient against epilepsy), which leads to a unique phase -ranging from clathrate to solvate to co-crystal- formed with an impressive number of apolar guest molecules (any linear alkanes to esters of fatty acids/alcohols, or waxes.). Moreover, the investig...

Brivaracetam, or (2S)-2-[(4R)-2-oxo-4-propyl-pyrrolidin-1-yl] butanamide, is an active pharmaceutical ingredient designed for the treatment of epilepsy. During the development of the IV administration mode, a liquid-liquid miscibility gap has been observed with pure water, isotonic and hypertonic solutions (vehicle at 0.9% w/w and 5%w/w NaCl respec...

Mechanochemical and solution based reactions of solid brivaracetam (BRV) and seletracetam (SEL), antiepileptic drugs from UCB's pipeline, with the inorganic salts MgCl2 and CaCl2, yield ionic co-crystals with changed or improved physico-chemical properties with respect to pure drugs (melting point, hygroscopicity, crystal morphology). All co-crysta...

Grinding of solid brivaracetam (BRV) and seletracetam (SEL) with inorganic lithium salts yields original ionic co-crystals (ICCs) characterized by markedly different thermal properties with respect to pure racetams; solid products have been characterized by single crystal crystallography. It is suggested that co-crystallizing lithium with some race...

Two in-line monitoring probes were inserted into a 3.2 L batch cooling crystallizer to monitor the progression of a dextrose monohydrate crystallization and how it was influenced by process variables including impurities, seed size and initial dextrose concentration. The probes used were a K-patents refractometer and a Lasentec FBRM probe. These pr...

The effects of impurities on dextrose monohydrate crystallization were investigated. Crystal nucleation and growth kinetics in the presence of impurities were studied using an in-line focused beam reflectance monitoring (FBRM) technique and an in-line process refractometer. Experimental data were obtained from runs carried out at different impurity...

This work focuses on the determination of the solid state nature of (RS)-2-(2-oxo-pyrrolidin-1-yl)-butyramide (Etiracetam), the racemic intermediate of (S)-2-(2-oxo-pyrrolidin-1-yl)-butyramide, an Active Pharmaceutical Ingredient, marketed under the name Levetiracetam(®). It is show how this information can easily be extracted from solid-liquid pha...

Mechanochemical reaction of solid piracetam with the inorganic salts LiCl and LiBr yields ionic co-crystals which are also co-drugs, characterized by markedly different thermal properties with respect to pure components, also depending on the method for preparation and/or conditions of measurements; single crystal and powder X-ray diffraction at va...

A batch seeded cooling crystallizer was used to study dextrose monohydrate crystallization. Experiments were conducted to investigate how a 2% increase in the initial dextrose concentration (from 65.5 to 67.5%) would influence final crystal yield and size. The crystallizations were performed for three different seed masses and cooling profiles, con...

The phase behaviour of the system poly(2,6-dimethyl-1,4-phenyleneoxide) (PPO) - antracene was investigated. An eutectic behaviour was deduced from calorimetric observations. In samples prepared by evaporation of a benzene solution, the melting point depression of both components and the eutectic melting was observed. When the samples are prepared b...

In this work, a seeded batch cooling crystallizer was used to study dextrose monohydrate crystallization using in situ techniques. Experiments were conducted to investigate the influence of cooling profile (natural, linear, and controlled cooling) and seed mass on dextrose monohydrate crystallization. Two in situ techniques, Lasentec focused beam r...

The polymorphism of sorbitol was investigated, confirming the existence of four anhydrous crystalline phases plus the hydrate. The crystallised melt (CM), the alpha form, and the gamma form were obtained via a dry route. The CM was confirmed to be a crystalline state with a spherulite morphology. The alpha form was obtained via direct conversion fr...

The goal of most crystallization processes is to improve filterability (reduction of fines) and to reach desired morphology and size of the crystals. The understanding of crystal size distribution variation with time is an important aspect of crystallization processes. It is also important to quantify changes in number and dimensions of crystals wi...

The Equivalent Cylinder Principle, as described in the literature, has been applied to the Brabender Viscograph in order to calibrate the instrument from a rheometrical point of view. Based on a calibration with a Newtonian fluid, the typical multi-pin geometry of the Viscograph is recalculated into a virtual concentric cylinder system. Applying st...

The complex problem of thermoreversible gelation of solutions of synthetic polymers is discussed. Several possible mechanisms, based on supramolecular structure formation in solution, are discussed. The gelation of polyethylene solutions illustrates the structure formation through lamellar, folded chain crystallization. Gelation of solutions of ste...

The complex problem of thcrmoreversibic gelation of solutions of synthetic polymers is discussed. Several possible mechanisms, based on supramoleeular structure formation in sclutioa. are discussed. The gelation of polyethylene solutions illustrates the structure formation through lamellar, folded chain crystallization. Gelation of solutions of ste...

The phase behaviour and the related morphology of the system high-density polyethylene/diphenyl ether was investigated. A liquid-liquid demixing precedes the crystallization in solutions with polymer weight fractions lower than 0,30. A three-phase equilibrium is installed, in which two liquid phases with different polymer concentrations and a cryst...