Analysis of the supercritical antisolvent mechanisms governing particles precipitation and morphology by in situ laser scattering techniques

Braeuer, Andreas; Dowy, Stefan; Torino, Enza; Rossmann, Matthias; Luther, S.; Schluecker, Eberhard; Leipertz, Alfred; Reverchon, Ernesto

doi:10.1016/j.cej.2011.07.064

Cited by 11 publications

(13 citation statements)

References 40 publications

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“…the thermodynamic and aerodynamic factors [69][70][71][72][73][74][75][76][77][78][79], and to the design of the particle collection environment [22]. Among the thermodynamic factors temperature, pressure conditions, rate of addition of one component to another and, phase and composition changes during the expansion can be listed.…”

Section: Influence Of Operating Parametersmentioning

confidence: 99%

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Nanoparticles in the Pharmaceutical Industry and the Use of Supercritical Fluid Technologies for Nanoparticle Production

Sheth

Sandhu²,

Singhal³

et al. 2012

CDD

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Poor aqueous solubility of drug candidates is a major challenge for the pharmaceutical scientists involved in drug development. Particle size reduction appears as an effective and versatile option for solubility improvement. Nanonization is an attractive solution to improve the bioavailability of the poorly soluble drugs, improved therapies, in vivo imaging, in vitro diagnostics and for the production of biomaterials and active implants. In drug delivery, application of nanotechnology is commonly referred to as Nano Drug Delivery Systems (NDDS). In this article, commercially available nanosized drugs, their dosage forms and proprietors, as well as the methods used for preparation like milling, high pressure homogenization, vacuum deposition, and high temperature evaporation were listed. Unlike the traditional methods used for the particle size reduction, supercritical fluid-processing techniques offer advantages ranging from superior particle size control to clean processing. The primary focus of this review article is the use of supercritical CO2 based technologies for small particle generation. Particles that have the smooth surfaces, small particle size and distribution and free flowing can be obtained with particular SCF techniques. In almost all techniques, the dominating process variables may be thermodynamic and aerodynamic in nature, and the design of the particle collection environment. Rapid Expansion of Supercritical Solutions (RESS), Supercritical Anti Solvent (SAS) and Particles from Gas Saturated Solutions (PGSS) are three groups of processes which lead to the production of fine and monodisperse powders. Few of them may also control crystal polymorphism. Among the aforementioned processes, RESS involves dissolving a drug in a supercritical fluid (SCF) and passing it through an appropriate nozzle. Rapid depressurization of this solution causes an extremely rapid nucleation of the product. This process has been known for a long time but its application is limited. Carbon dioxide, which is the only supercritical fluid that is preferentially used in pharmaceutical processes, is not a good solvent for many Active Pharmaceutical Ingredients (API). Various researchers have modified the RESS process to overcome its solubilizing limitations, by introducing RESOLV, RESAS, and RESS-SC. Overall, all RESS based processes are difficult to scale up. The SAS processes are based on decreasing the solvent power of a polar organic solvent in which the substrate (API & polymer of interest) is dissolved, by saturating it with carbon dioxide (CO2) at supercritical conditions. CO2 causes precipitation and recrystalization of the drug. SAS is scalable and can be applied to a wide variety of APIs and polymers. Minor modifications of basic SAS process include GAS, ASES, SAS-DEM and SAS-EM. Processes where SCF is used as an anti solvent and dispersing agent include SEDS, SAA, and A-SAIS. The mechanisms and applications of these processes were briefly discussed. In PGSS, CO2 is dissolved in organic solutions or melted compound...

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Section: Influence Of Operating Parametersmentioning

confidence: 99%

“…The same group further demonstrated the proposed mechanism via in situ laser scattering techniques. They were able to study the location of first particle precipitation inside the vessel, the partial densities of all species in the system, the supersaturation, and overall mixture composition [79].…”

Section: Pharmaceutical and Biomedical Applications Referencesmentioning

confidence: 99%

Nanoparticles in the Pharmaceutical Industry and the Use of Supercritical Fluid Technologies for Nanoparticle Production

Sheth

Sandhu²,

Singhal³

et al. 2012

CDD

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“…Acetone and dimethyl sulfoxide (DMSO) have been used as organic solvents, while CO 2 has been used as the bulk supercrit ical phase. These substances have been chosen, as they are frequently used in the supercritical fluid technolo gy to precipita te particles according to the supercritical antisolvent technology [6][7][8], and as information about their vapor-liquid equilibria has been reported numerously [9,10]. Furthermore acetone represents a volatile compound with low surface tension with respect to DMSO.…”

Section: Mass Transfer At Supercritical Conditionsmentioning

confidence: 99%

Quantification of the mass transport in a two phase binary system at elevated pressures applying Raman spectroscopy: Pendant liquid solvent drop in a supercritical carbon dioxide environment

Braeuer¹,

Knauer²,

Quiño³

et al. 2013

International Journal of Heat and Mass Transfer

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“…Lastly, it has to be highlighted that several works of in situ measurements have been reported over the last decade contributing to filling the gaps [56][57][58]. Indeed, different methods such as in situ FTIR measurements or in situ laser scattering allow a deeper study of polymer swelling or CO 2 uptake, and in a more general way a study of the different interactions between the drug solutes, polymers and SC CO 2 .…”

Section: Knowledge Gaps/needsmentioning

confidence: 99%

Current situation and perspectives in drug formulation by using supercritical fluid technology

Badens

Masmoudi

Mouahid

et al. 2018

The Journal of Supercritical Fluids

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Supercritical fluid (SCF) technology has been applied to drug product development over the last thirty years and drug particle generation using SCFs appears to be an efficient way to carry out drug formulation which will form end-products meeting targeted specifications. This article presents an overview of drug particle design using SCFs from a rather different perspective than usual, more focused on chemical and process engineering aspects. The main types of existing processes are described in a concise way and a focus is put on how to choose the right operating conditions considering both thermodynamic and hydrodynamic aspects. It is shown that the operating conditions and parameters can be easily optimized so as to facilitate the further process scale-up. Furthermore, the new trends in particle generation using SCFs are introduced, related either to new types of drug medicines that are treated or new ways of process implementation methods.

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Analysis of the supercritical antisolvent mechanisms governing particles precipitation and morphology by in situ laser scattering techniques

Cited by 11 publications

References 40 publications

Nanoparticles in the Pharmaceutical Industry and the Use of Supercritical Fluid Technologies for Nanoparticle Production

Nanoparticles in the Pharmaceutical Industry and the Use of Supercritical Fluid Technologies for Nanoparticle Production

Quantification of the mass transport in a two phase binary system at elevated pressures applying Raman spectroscopy: Pendant liquid solvent drop in a supercritical carbon dioxide environment

Current situation and perspectives in drug formulation by using supercritical fluid technology

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