AFNS/CEE Special Lecture by Prof. Elisabeth Badens: “Supercritical fluid technology for innovation in drug product and medical device development”

DEPARTMENT OF AGRICULTURAL, FOOD AND NUTRITIONAL SCIENCE

&

DEPARTMENT OF CIVIL AND ENVIRONMENTAL ENGINEERING

 “Supercritical fluid technology for innovation in

drug product and medical device development”

Special Lecture by Visiting Professor

Dr. Elisabeth Badens

Professor of Chemical Engineering

Aix-Marseille University, CNRS, Centrale Marseille, M2P2 Laboratory, Marseille, France

Tuesday, October 25, 2022 at 3:00 pm

8-207 Donadeo Innovation Centre for Engineering

(Hosts: Feral Temelli, AFNS and Selma Guigard, CEE)

 Abstract:

Supercritical fluid technology is increasingly applied in the pharmaceutical and medical device industries. The use of supercritical CO₂ (scCO₂) allows the development of environmentally friendly processes. leading to products complying with stringent regulatory requirements.

In this talk, first the latest developments for the elaboration of drug formulations in supercritical media will be presented. In recent years, processes for drug particle generation using scCO₂ have been implemented in the industry [1, 2]. The main advantages of these processes will be highlighted and concrete examples for pure drug particle formation and sustained release drug delivery systems will be given. Not only the particle size but also the crystal habit and polymorphism can be controlled [3, 4] and thus it is possible to control the drug release characteristics of the end product. Lastly, the use of supercritical fluid technology for the development of alternative therapy solutions to conventional medicinal ones will be addressed. Examples of formulations of small molecules of ribonucleic acids (RNAs) or of antibodies elaborated through a supercritical route will be presented.

The second part will be dedicated to supercritical treatment of medical devices (MD). scCO₂ is already used at industrial scale for MD cleaning, mostly for degreasing. The purpose is generally to remove different contaminants such as oils, greases, waxes, lubricants, fats, resins, etc. scCO₂ is as efficient as perchloroethylene but has the advantage of being non-toxic. In comparison with water and detergent methods, the treatment duration is shorter and does not involve a further drying step. Moreover, the cleaning can be performed under mild conditions of temperature, often at 35-40 °C. Concrete examples of scCO₂ cleaning in the French industry will be provided.

The biocidal properties of scCO₂ [5] are a true asset for this application field. Indeed, the cleaning of DM is a pre-sterilization step, where a significant bioburden lowering is observed, allowing the subsequent sterilization step to be shorter. The objective of the current research is to achieve complete sterilization of DM with scCO₂. Since the sterilization can be conducted using similar equipment needed for cleaning, there is a real potential for gaining efficiency by implementing an integrated process of scCO₂ cleaning and sterilization. An ongoing French collaborative project aiming to draw up a draft of sterilization standards will be presented.

Drug incorporation into MD using scCO₂ has received growing interest based on studies over the last 20 years [1, 2, 6, 7]. Sustained release drug delivery systems can be obtained by supercritical drug impregnation into MD. Depending on the nature of the solute to be impregnated and the MD material, the impregnation can be carried out without the use of a co-solvent. The drug can be molecularly dispersed in a uniform manner, which is hardly possible by soaking into liquid organic solutions. scCO₂ technology is undoubtedly an efficient method for loading drugs into polymeric implants or prosthesis to have a sustained release of the active molecule after the DM implantation in the body. An update of these different applications will be given with a particular attention to the preliminary studies (measurement of polymer swelling, of CO₂ sorption, drug solubility in CO₂) that have to be carried out [6] and to the operating conditions (pressure, temperature, dynamic or static mode, pressurization and depressurization rates) that have to be used [7] for optimizing the processes and for preserving the MD properties. Applications of different Technology Readiness Levels (TRL) will also be presented.

References

1. E. Badens, Supercritical fluid technology in pharmaceuticals – State of the art and future trends, Les Techniques de l’Ingénieur, CHV4010EN, 2017.
2. E. Badens et al., Current situation and perspectives in drug formulation by using supercritical fluid technology, The Journal of Supercritical Fluids, 134, 2018.
3. S. Clercq et al., Investigation of crystallization mechanisms for polymorphic and habit control from the Supercritical AntiSolvent process, The Journal of Supercritical Fluids, 141, 2018.
4. S. Clercq et al., Prediction of crystal-solvent interactions in a supercritical medium: A possible way to control crystal habit at high supersaturations with molecular modeling, Journal of Crystal Growth and Design, 20, 6863, 2020.
5. Soares, G. et al., Supercritical CO₂ technology: The next standard sterilization technique?, Material Science Engineering C, 99, 2019.
6. K. Ongkasin et al., Supercritical loading of gatifloxacin into hydrophobic foldable intraocular lenses – Process control and optimization by following in situ CO₂ sorption and polymer swelling, International Journal of Pharmaceutics, 581, 2020.
7. J.M. Andre, E. Badens, O. Forzano, Y. Masmoudi, Patent “« Process for the elaboration of polymeric implants or prosthesis », F96 12FR 01-2012, F96 12EUR 01-2017, F96 12CN 01-201.