P.J. Jansens

Hyperbranched Polymers as Drug Carriers: Microencapsulation and Release Kinetics

The aim of this work was to study the feasibility of hyperbranched polymers as drug carriers by employing different microparticle formation methods and the influence of loading methods on release kinetics. Commercially available hyperbranched polyester (Perstorp) and three polyesteramides (DSM) were loaded with the pharmaceutical acetaminophen. The gas antisolvent precipitation (GAS), the coacervation, and the particles from gas saturated solutions (PGSS) are among conventional processes that were used to prepare microparticles of drug-loaded hyperbranched polyesters for the first time. For preparing solid dispersions of drug-loaded hyperbranched polyesteramides the solvent method was applied. Infrared (IR) and differential thermal analysis (DTA) studies suggest that acetaminophen is partly dissolved in the polymer matrix and partly crystallized outside the polymer matrix. For acetaminophen-loaded polyesters prepared by the GAS method, the presence of free drugs is predominant when compared to microparticles prepared by the coacervation method. This event disappears for microparticles prepared by the PGSS method. Moreover, the release of drug from drug-loaded Bol-GAS is biphasic, where the initial burst (48%), indicating the presence of unincorporated drugs, is followed by a slow-release phase, suggesting the diffusion of drug through polymer matrices. The release of drugs from drug-loaded Bol-PGSS do not show this behavior since the drug is better dissolved or dispersed in polymer matrices. In the case of drug-loaded polyesteramides, coevaporates prepared from 3 hyperbranched structures (H1690, H1200, and H1500) using the solvent method result in different release kinetics. The hydrophobic characteristic of hyperbranched polyesteramide H1500 shows the biphasic release kinetic whereas the drug released from hydrophilic matrices H1690 and H1200 exhibits fast release comparable to that of pure drug.

Lipase-Catalyzed Ethanolysis of Milk Fat with a Focus on Short-Chain Fatty Acid Selectivity

Mixtures of fatty acid ethyl esters were produced by lipase-catalyzed ethanolysis of milk fat triglycerides. Three commercial immobilized lipases (Lipozyme TL, Lipozyme RM, and Novozym 435) were tested in different reaction conditions with the aim of maximizing the conversion of the short-chain fatty acid fraction of milk fat to flavor ethyl esters. The influence of the reactants molar ratio was investigated, as well as three different reaction media, that is, hexane, CO(2)-expanded liquid (GXL), and the solvent-free mixture. Novozym 435 showed the highest activity in all conditions. This lipase also exhibited selectivity for short-chain fatty acids, which, at short reaction times, resulted in a product mixture richer in short-chain fatty acids than the original milk fat. The highest selectivities were obtained in hexane and in CO(2)-expanded liquid fat, at low ethanol to fat ratios. Using dense CO(2) as the reaction cosolvent is attractive because it results in the largest short-chain fatty acid enrichment in the product mixture, while leaving no residues in the product.

Experimental characterization and computational fluid dynamics simulation of gas distribution performance of liquid (re)distributors and collectors in packed columns

The usability of a state of the art computational fluid dynamics simulation package as a tool for analyzing the fluid-dynamic performance of internals encountered in packed distillation columns, such as initial gas distributors, liquid distributors and liquid collectors is demonstrated. A 1.4 m internal diameter column hydraulics simulator was used to provide detailed experimental evidence on the gas distribution pattern imposed by various types of column internals. The comparison of measured and predicted profiles for single-phase gas flow conditions indicates a strikingly good agreement.

Molecular modelling of the crystallization of polymorphs. Part I: The morphology of HMX polymorphs

A molecular modelling procedure for the prediction of interfacial energies between polymorphs and solvents is under development. The first step in such a procedure must be to determine and investigate the structure of the possible morphologically important crystal surfaces. This is done for two of the experimentally readily obtained polymorphs β-HMX and α-HMX (cyclotetramethylene tetramine) by means of a periodic bond chain analysis.

The application of a task-based concept for the design of innovative industrial crystallizers

A new task-based design approach [Menon, A. R., Pande, A. A., Kramer, H. J. M., Grievink, J., & Jansens, P. J. (2007). A task-based synthesis approach toward the design of industrial crystallization process units. Industrial & Engineering Chemistry Research, 46, 3979] is applied to design a crystallization process unit. Task-based design involves the conceptual built-up of a process (unit) from functional building blocks called tasks, which represent fundamental physical events. The motivation for developing this approach is to get a better control over the physical events governing crystalline product quality. To deliver a proof of concept, two lines of research are followed. First of all, several small scale experiments are designed to demonstrate practical feasibility of the approach. The new equipment allows for isolation and manipulation of individual crystallization tasks. Second, a model based on the experimentally tested tasks is developed for a crystallizer design and used in dynamic optimization of three case studies. The results show that completely different and tight product specifications can be achieved with the same design simply by changing the operational policy of the crystallizer. This remarkable increase in flexibility to achieve a broad range of product qualities is the result of the ability to control the rate at which individual crystallization tasks are executed as well as the material flows between those tasks.

Development of a Vacuum Crystallizer for the Freeze Concentration of Industrial Waste Water

Freeze concentration has proven to be a viable technology for the concentration of hazardous industrial waste waters before incineration. Owing to the relatively high investment cost of the technology, its applicability has been limited until now. This paper investigates the feasibility of a vacuum crystallizer as potential replacement of the scraped surface heat exchanger, which is one of the most cost- and maintenance-intensive items in conventional freeze concentration technology. Different crystallizer configurations and vapour treatment methods were evaluated for the system design. A thermodynamic analysis was performed to predict the phase transition behaviour in the condenser. A hydrodynamic analysis was performed to establish design rules and to determine the operating window. Finally, the principle of vacuum freeze crystallization was proven experimentally.

Morphology of ϵ-caprolactam crystals dependent on the crystallization conditions

Abstract The morphology of caprolactam crystals is an important property because it can affect their filterability. This study shows that the morphology of caprolactam crystals depends on the water content of the mother liquor and on the applied growth kinetics. Needle-like crystals were formed during single crystal experiments under two sets of conditions: (1) at high growth rates in a water rich mother liquor and (2) at low growth rates in the absence of water. Experiments were also performed in a lab-scale batch crystallizer and in a pilot-scale continuous crystallizer but did not yield exclusively needle-like crystals.

Design of a Multi-Functional Crystallizer for Research Purposes

The design procedure and the specifications for the design process and the resulting experimental set-up of a multi-functional 75l pilot plant crystallizer are described. The crystallizer can operate in different operational (batch/continuous) and crystallization modes (cooling/flash–cooling/evaporative). This flexibility enables the generation of experimental information on the relationship between process conditions and product quality for different model compound systems using one crystallizer. The design is realized using a hierarchical design procedure described previously, which is extended with an additional level for the design of instrumentation and control. The design procedure is useful to structure the design process of a pilot plant crystallizer and to identify design problems at an early stage. A description of the pilot plant crystallizer, a design synthesis model, a flowsheet design and an investment cost estimation of the experimental set-up and the cost of this infrastructure per typical experiment are presented. The designed pilot plant was actually built and successful crystallization experiments have been performed. However, the deviation seen between the median crystal sizes as specified as design target and the measured one in the realized crystallizer illustrates the need for a rigorous predictive crystallizer model to further analyse and optimize a design.

Growth behaviour of crystals formed by primary nucleation on different crystalliser scales

The growth behaviour of small ammonium sulphate crystals obtained from primary nucleation in different crystallisers were studied. The results revealed a broadening of the distribution upon growth of the crystals that is attributed to growth rate dispersion. This phenomenon was somewhat more pronounced in experiments with the fines imported from a 1100 l draft tube baffled crystalliser compared to those generated in a 2 l cooling crystalliser. This small difference in the growth behaviour between the crystals originating from the two crystallisers, however, does not allow one to reject the hypothesis that the outgrowth of the crystals originating from either primary and secondary nucleation is identical for a small and for a large-scale crystalliser. The growth behaviour of these crystals was simulated using a size-dependent growth model. The simulation results revealed that the growth model (Chem. Eng. Sci. 54 (1999) 1273,1283) is capable of simulating trends in the supersaturation and the median crystal size but was not able to describe the observed broadening of the crystal size distribution.

The use of self-interaction chromatography in stable formulation and crystallization of proteins

This paper reviews the basic principles of the recently developed self‐interaction chromatography (SIC) technique with regard to protein solution stability and protein crystallization. It gives experimental protocols for both normal‐scale and micro‐scale SIC experiments and reviews recent developments and current applications of this novel technique in the biopharmaceutical area. This paper aims to be a benchmark in the further proliferation of this highly effective and fast technology for the rational design of stable aqueous formulations of therapeutic proteins and the determination of solution conditions favoring protein crystallization.