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Our systems are designed to satisfy every kind of request in supercritical CO2 processing, thanks to the programmable configurations by software recipes. However, there are some needs that require dedicated solutions. URS designs and standard options are available.

Design on request

Separeco has one of its strongest points in the design based on URS. We can design extraction, fractionation, micronization systems adapting them to the specific needs of the customer. We carry out bibliographic research and preliminary tests to establish the best process conditions to accurately determine the characteristics that the machinery must have to achieve the required result. The procedure starts from the customer’s URS. On the basis of the requests, the possible solutions will be analyzed and the hardware and software strategies will be identified, writing all the essential documents such as the DDS (Detailed Design Specifications) and the FRS (Functional Requirements Specifications), documents that will be cross-checked in the DQ (Design Qualification). The manufactured system is finally tested with the customer during FAT (Factory Acceptance Test) to verify all the documents and performance of the machinery.

Co-solvent pump

It is the most important option. With the co-solvent pump it is possible to change the polarity of the CO2 to extract a wider range of compounds from the loaded matrix. The automation of the machine manages both the flow rate and the moment in which the pump starts and for how long the CO2 is modified by the co-solvent. Ethanol or blends of ethanol or other allowed liquid solvents but functional to the desired extraction process, can be used. It is also very useful for increasing the solvent capacity when the raw material is particularly poor in the target compounds. It is also essential for carrying out a good cleaning of the system, using the cleaning recipe that operates without having to open any vessel (CIP). The pump also comes in a kit with the Coriolis effect flow meter, the electronic inverter that controls the pump motor, software, pipe lines, automatic, manual and check valves.

Additional separator S0

S0 additional separator is designed to be controlled in temperature and pressure, independently from extractor pressure. As it’s the first in the separators chain, it is possible to control it in pressure up to 170 bar (2460 psi). After the extracted compounds leave the extraction vessel(s) they travel to separation vessels. By varying the pressure, flow and temperature of these vessels, it is possible to exploit difference in compounds solubility in order to achieve high degree of fractional separation. The intent of selecting these parameters is to induce the selective precipitation of different compound families as a function of their different saturation conditions in the supercritical fluid (SCF). First, consider the pressure reduction that takes place after back-pressure valve (positioned immediately downstream the extractors). Based upon on the pressure set point, we can observe two different effects:

a. if the pressure set point is below the critical point, we have gaseous CO2 inside Separator S1. This result is essential in the SCF extraction. Two important effects are observed:

1. density of the fluid is reduced of 10 folds and the expansion of the CO2 changes the speed of the CO2 from cm to m per second,
2. all compounds dissolved in the CO2 immediately fall down because the fluid changed its status from supercritical to gaseous and now is become a very bad solvent.

All these changes cause a consequence: because of Joule-Thomson effect (the rapidly-expanded gas during depressurization process cools because the molecules get the energy using their specific heats), the temperature of the gaseous CO2 falls down dramatically. Solids like wax or paraffin immediately become solid and the risk to clog the pipes is high. To prevent this problem, an exchanger is added immediately after the back pressure valve. The heaviest compounds are collected here while the other compounds travel to Separator #2 and #3.

b. if the pressure set point is above the critical point, we have a supercritical CO2 inside Separetor S1. This is the case of the S0 additional separator. Fluid expansion is reduced and the effects described above are no more observed or dramatically decreased. What happens to the solute is different than before. Downstream the back-pressure valve we have still a supercritical fluid and not a gas. No status change this time, therefore different effects. As explained above, solubility is function of pressure/temperature.
Changing pressure and temperature the solubility of the fluid is altered, not null as before: still a good solvent but with different characteristics. Process engineers use this effect to collect only the compounds that are no longer in solution at those conditions. The rest travel to Separator #2 and #3.

GMP and GAMP5

GAMP focuses on the whole system and the end product, where as the FDA focuses on each process and stage of production that contributes to the end product. FDA guidances are incorporated into the GAMP guidelines.
As the GAMP 5 guidelines have “Automated” built into the name and their philosophy – they envision process and system (computer) validation as integrated entities. An automated process is tested as an installation, operational, and performance qualification to be certain that the automated procedure has been properly installed, tested, and used. By contrast, the FDA’s GMP document assumes a manual process with reference to the reality of automated process systems through the separate document 21 CFR Part 11, which defines system validation and provides guidelines for it. The GAMP stresses bottom- line performance, while the FDA stresses the process itself (procedurally and with automation).
Under GAMP 5, an investigator would validate the results of an automated analysis system as a functioning analytical unit.
Under GMP, an investigator would validate the analytical process of each step of the process.
Similarly, the GAMP focuses on quality assurance (QA). While still emphasizing QA, the FDA approach puts equal weight on the quality control (QC) process, including all aspects of production and operation as well as the final QA overview. The result is, the FDA has a greater reliance on analysis at all phases, where GAMP has reliance on the final result rather than the interim steps that lead to that result. In short, process understanding (FDA) versus process outcome (GAMP).

AISI 316

There are different grades of stainless steel like 302, 304, 316, 410, 430, etc… Not all are used in pharmaceutical machinery. The guide line to choose the right material is its resistence to solvents, active materials or eccipients used in the production. Most common types of stainless steel used in the construction of pahrmaceutical equpment are AISI 304 and AISI 316. Stainless steel AISI 316 is more resistant than AISI 304 against acid and base attacks. Weack acids and bases have no important effect on stainless steel. However, when supercritical/liquid CO2 comes into contact with water, carbonic acid is formed. Although carbonic acid is considered to be a weak acid, the safest indication is to use 316 steel for the parts in contact with the extract and 304 for the parts not in contact with the extract. This solution, although slightly more expensive, will allow you to protect yourself from any objection or exception by the certification bodies. Best choice is the duplex stainless steel, like SAF 2205, when the industrial systems are designed. Stronger than AISI 316, it reduces dramatically the thikness at compared pressure.

Industry 4.0

Industry 4.0 is the digital transformation of manufacturing/production and related industries and value creation processes. Industry 4.0 refers to the intelligent networking of machines and processes for industry, based on information and communication technology. It is a process that stems from the “fourth industrial revolution” and is leading to fully automated and interconnected industrial production. The new digital technologies will have a profound impact in the context of four development guidelines.
The first concerns the use of data, computing power and connectivity and is divided into big data, open data, Internet of Things, machine-to-machine and cloud computing for information centralization and storage.
The second is that of analytics: once the data is collected, it is necessary to derive value from it. Today only 1% of the data collected is used by companies, which could instead obtain advantages starting from “machine learning”, that is, from machines that improve their performance by “learning” from the data gradually collected and analyzed.
The third direction of development is the interaction between man and machine, which involves “touch” interfaces, which are increasingly widespread, and augmented reality. Finally, there is the whole sector that deals with the transition from digital to “real” and which includes additive manufacturing, communications, machine-to-machine interactions and new technologies for storing and using energy in a targeted way, rationalizing costs and optimizing performance.