Alain Chamayou

Talc grinding in an opposed air jet mill: start-up, product quality and production rate optimization

We present a study of talc grinding in an Alpine 100 AFG opposed air jet mill with an inline laser granulometer. The conditions for steady state operation have been determined from continuous grinding experiments and show that overloading occurs above a critical value of feed rate classifier resulting in unstable product size distribution. For each rotation speed of the classifier, there is an optimum feed rate, which gives the finest product, thus fixing a maximum reduction ratio. A linear relation exists between this ratio and the rotation speed of the classifier. The use of liquid grinding aids have been studied and showed they can result in an increase in the production rate but can also lead to a coarser product.

Engineering of nano-crystalline drug suspensions: Employing a physico-chemistry based stabilizer selection methodology or approach

This paper describes a systematic approach to select optimum stabilizer for the preparation of nano-crystalline suspensions of an active pharmaceutical ingredient (API). The stabilizer can be either a dispersant or a combination of dispersant and wetting agent. The proposed screening method is a quick and efficient way to investigate a large number of stabilizers based on the principles of physical-chemistry and employs a stepwise approach. The methodology has been divided in two main parts; the first part being focused on the qualitative screening with the objective of selecting the best candidate(s) for further investigation, the second part has been focused on quantitative screening with the objective to optimize the ratio and amount of wetting and dispersing agents, based on wettability, surface charges measurement, adsorption evaluation, process-ability evaluation and storage stability. The results showed clearly that SDS/PVP 40/60% (w/w) (sodium dodecyl sulfate/poly(vinyl pyrrolidone)) at a total concentration of 1.2% was the optimum stabilizer composition, at which the resulting nanosuspensions were stable for more than 50 days at room temperature.

Chapter 8 Air Jet Milling

Publisher Summary This chapter talks about air jet milling. The first versions, developed in the late 19th century, used a jet of compressed air to project solids against a target. Such devices have the severe disadvantage of target wear and subsequent contamination of the products but have lead to the development of other versions with opposed jets, tangential intersecting jets and more recently opposed jets in a fluidized bed. Air jet milling, or more correctly fluid energy milling, uses high velocity jets of gas to impart energy to particles for size reduction. Air jet mills have mainly been developed for producing fine particles of below 50 mm. Most models are available in many sizes from lab-size versions (as low as to 1 gram/h) up to industrial versions (up to 6 tonne/h), making for easy testing and scale-up. However, a disadvantage is that air jet mills require ancillary air compressors that can assure high flow rates at pressures up to about 10 bars. In addition, the chapter also discusses different types of air jet mills.

Radicalar probes to measure the action of energy on granular materials

Abstract Measuring the action of energy on matter is a complex problem, especially in the case of granular materials. For example, particle size reduction by grinding generally shows poor overall energetic yields and a significant challenge in this area is to accurately estimate the energy consumed, including that stored in the particles. Fine or ultra-fine grinding processes require a lot of energy, part of which becomes internal energy and can lead to mechanochemical reactions and useful products. We studied the appearance of free radicals during the grinding of α-lactose monohydrate by means of electron spin resonance (ESR). These radicals are the same as those induced by γ-radiation and comparison of ESR spectra intensities with those from ground products allows the determination of an ‘equivalent γ-irradiation dose’. This gives a novel concept for characterizing the action of mechanical energy on matter in fine grinding by using molecular probes. This is the first example of the investigation of mechanochemical energy during the fine grinding process.

Mechanochemical Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity

A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as phenolic hydrazine 1a and almost all heteroaromatic ones, especially 2, 5 and 7, are more active than isoniazid, and their activity against some M. tuberculosis MDR clinical isolates was determined. Compounds 1a and 7 present a selectivity index >1400 evaluated on MRC5 human fibroblast cells. The mechanism of action of selected hydrazones was demonstrated to block mycolic acid synthesis due to InhA inhibition inside the mycobacterial cell.

Assessment of formulation robustness for nano-crystalline suspensions using failure mode analysis or derisking approach

The small particle size of nano-crystalline suspensions can be responsible for their physical instability during drug product preparation (downstream processing), storage and administration. For that purpose, the commercial formulation needs to be sufficiently robust to various triggering conditions, such as ionic strength, shear rate, wetting/dispersing agent desorption by dilution, temperature and pH variation. In our previous work we described a systematic approach to select the suitable wetting/dispersant agent for the stabilization of nano-crystalline suspension. In this paper, we described the assessment of the formulation robustness (stabilized using a mixture of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone (PVP) and) by measuring the rate of perikinetic (diffusion-controlled) and orthokinetic (shear-induced) aggregation as a function of ionic strength, temperature, pH and dilution. The results showed that, using the SDS/PVP system, the critical coagulation concentration is about five times higher than that observed in the literature for suspension colloidaly stable at high concentration. The nano-suspension was also found to be very stable at ambient temperature and at different pH conditions. Desorption test confirmed the high affinity between API and wetting/dispersing agent. However, the suspension undergoes aggregation at high temperature due to the desorption of the wetting/dispersing agent and disaggregation of SDS micelles. Furthermore, aggregation occurs at very high shear rate (orhokinetic aggregation) by overcoming the energy barrier responsible for colloidal stability of the system.

Dry coating in a high shear mixer: Comparison of experimental results with DEM analysis of particle motions

Experimental dry coating of guest particles on the surface of host particles is performed by mechanical forces in a high shear mixer called “Cyclomix”. The studied system (a mixture of particles of sugar, “Suglet™” as host particles and magnesium stearate as guest particles) was chosen as a model one to achieve better understandings of the phenomena during mixing. To simulate the flow of host/guest particles in the mixer, the Discrete Element Method (DEM) was applied. Experimental results such as flowability and wettability can be explained by particles flows evolutions with different rotational speed or duration treatment inside the Cyclomix.

Processing of Food Powders

The development of formulation engineering concepts in food manufacturing and the demand for diversity in food products has driven a substantial market increase for food ingredients. Most ingredien ...