Imprégnation par voie CO2 supercritique pour préparer des implants polymère à libération contrôlée de principes actifs (original) (raw)
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Supercritical CO2 Assisted Impregnation to prepare Drug-eluting Polymer Implants
2014
The scCO2 impregnation process is a promising alternative to other manufacturing process to prepare drug-eluting polymer implants.This work enabled to rationalize the influence of the key parameters governing this process and to determine in which extent this process can be used to prepare drug-eluting implants. We have combined the information obtained with traditional polymer characterization techniques and a newly characterization set-up we have developed that is based on in situ FTIR micro-spectroscopy. We have worked on the impregnation of sutures made of PLLA, PP and PET with two anti-inflammatory drugs namely ketoprofen and aspirin.Firstly, the thermodynamic behaviors of the systems drug/CO2 (solubility and speciation of the drug) and polymer/CO2 (CO2 sorption, polymer swelling, evolution of the polymer microstructure and of the tensile properties) were studied as a function of pressure and temperature. Then, the scCO2 impregnation process was investigated. The impact of the ...
Drug loading of polymer implants by supercritical CO 2 assisted impregnation: A review
Journal of Controlled Release, 2015
Drug loaded implants also called drug-eluting implants have proven their benefits over simple implants. Among the developed manufacturing processes, the supercritical CO 2 (scCO 2) assisted impregnation has attracted growing attention to load Active Pharmaceutical Ingredients into polymer implants since it enables to recover a final implant free of any solvent residue and to operate under mild temperature which is suitable for processing with thermosensitive drugs. This paper is a review of the state-of-the-art and the application of the scCO 2 assisted impregnation process to prepare drug-eluting implants. It introduces the process and presents its advantages for biomedical applications. The influences of the characteristics of the implied binary systems and of the experimental conditions on the drug loading are described. Then, the various current applications of this process for manufacturing drug-eluting implants are reviewed. Finally, the new emerging variations of this process are described.
Supercritical CO2 impregnation of polyethylene components for medical purposes
Hemijska industrija, 2007
Modem hip and knee endoprosthesis are produced in titanium and to reduce the friction at the contact area polymer parts, mainly ultra-high molecular weight polyethylene (UHMW-PE), are installed. The polyethylene is impregnated with a-tocopherol (vitamin E) before processing for remarkable decrease of oxidative degradation. Cross linked UHMW-PE offers much higher stability, but a-tocopherol cannot be added before processing, because a-tocopherol hinders the cross linking process accompanied by a heavy degradation of the vitamin. The impregnation of UHMW-PE with a-tocopherol has to be performed after the cross linking process and an accurate concentration has to be achieved over the cross section of the whole material. In the first tests UHMW-PE-cubes were stored in pure a-tocopherol under inert atmosphere at temperatures from 100 to 150 ?C resulting in a high mass fraction of a-tocopherol in the edge zones and no constant concentration over the cross section. For better distribution ...
The Journal of Supercritical Fluids, 2009
Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused drug were evaluated together with the impregnated drug stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the drug over a long period of time.
Ibuprofen Impregnation into Submicron Polymeric Films in Supercritical Carbon Dioxide
The Journal of Supercritical Fluids, 2012
The impregnation of ibuprofen into submicron films (25–250 nm) of poly(methyl methacrylate), PMMA, under supercritical CO2 conditions (at 40 °C and 50 °C and 13.8 and 20.7 MPa) was studied. The quartz crystal microbalance (QCM) was used to perform real-time, in situ impregnation measurements. The amount of ibuprofen uptake into the polymer film was calculated directly from the QCM results. Different aspects of the process were studied including: the effect of CO2 density on uptake, distribution uniformity across the film thickness, and impregnation rate. The partitioning coefficient of ibuprofen PMMA and CO2 was high, whereas the diffusivity of ibuprofen was found to be order of magnitudes lower than that of CO2. These two effects are believed to result in high drug loading in the polymer. It was also concluded that CO2 helped in producing uniform concentration profiles of ibuprofen in the PMMA films. Finally, preliminary studies on the impregnation of poly(vinyl pyrrolidone), PVP, with ibuprofen were performed. The QCM response in the case of PVP films was significantly larger than that with PMMA at the same conditions. Some possible causes for this unusual behavior are discussed.► Ibuprofen does not induce significant plasticization effect in PMMA films during impregnation. ► Due to its swelling effect, CO2 seems to provide efficient impregnation throughout the thickness of the polymer film. ► Evidence of Fickian diffusion behavior for Ibuprofen in PMMA is observed. ► While PVP shows good agreement with literature values in terms of CO2 absorption, its IBU absorption behavior showed large variations that could not be explained based on IBU impregnation.
The Future of Carbon Dioxide for Polymer Processing in Tissue Engineering
Tissue Engineering Part B: Reviews, 2013
The use of CO 2 for scaffold fabrication in tissue engineering was popularized in the mid-1990s as a tool for producing polymeric foam scaffolds, but had fallen out of favor to some extent, in part due to challenges with pore interconnectivity. Pore interconnectivity issues have since been resolved by numerous dedicated studies that have collectively outlined how to control the appropriate parameters to achieve a pore structure desirable for tissue regeneration. In addition to CO 2 foaming, several groups have leveraged CO 2 as a swelling agent to impregnate scaffolds with drugs and other bioactive additives, and for encapsulation of plasmids within scaffolds for gene delivery. Moreover, in contrast to CO 2 foaming, which typically relies on supercritical CO 2 at very high pressures, CO 2 at much lower pressures has also been used to sinter polymeric microspheres together in the presence of cells to create cell-seeded scaffolds in a single step. CO 2 has a number of advantages for polymer processing in tissue engineering, including its ease of use, low cost, and the opportunity to circumvent the use of organic solvents. Building on these advantages, and especially now with the tremendous precedent that has paved the way in defining operating parameters, and making the technology accessible for new groups to adapt, we invite and encourage our colleagues in the field to leverage CO 2 as a new tool to enhance their own respective unique capabilities.
Chemotherapeutic implants via subcritical CO2 modification
Biomaterials, 2007
Polymer-based biomaterials have a broad range of current applications in medicine. Many implants generate a favorable biomedical outcome solely by providing short-term mechanical stability that allows healing of the surrounding tissues. An example is polymeric reconstructive resorbable plates having initial strengths sufficient to stabilize bone segments while allowing the osteosynthesis needed to restore original function following tumor resection. Simultaneous, localized delivery of the widely employed chemotherapeutic paclitaxel following tumor removal presents a particularly desirable goal in this context. By using compressed/subcritical CO 2 at moderate pressures (as opposed to the more familiar supercritical pressures) to embed paclitaxel in clinically utilized reconstructive plating, the form of the implant can be preserved while adding an inherently localized chemotherapeutic function. In vitro tests demonstrate the efficacy of the embedded paclitaxel against adherent MCF-7 breast cancer cells within the immediate area of the polylactic acid (PLA). CO 2 can be utilized to add dual structural-chemotherapeutic function to polymeric surfaces without a change in form. The ability to 'piggyback' chemotherapeutic function into nearly any polymeric surface should find widespread utility. r
Journal of Materials Science, 2008
Supercritical carbon dioxide (SCCO 2) was used for the preparation of foamed sponges and intermingled fibers of biopolymers with potential applications in tissue engineering and drug delivery. The work was focused on the processing of both biodegradable polylactic acid (L-PLA) and non-biodegradable polymethylmethacrylate (PMMA) homopolymers. Monolithic porous sponges of amorphous PMMA were prepared using SCCO 2 as a porogen agent by simple swelling and foaming. Under similar experimental conditions, L-PLA was crystallized. The study also addresses the impregnation of biopolymers with an active agent dispersed in SCCO 2. The drug used for impregnation was triflusal, a platelet antiaggregant inhibitor for thrombogenic cardiovascular diseases. Foaming often leads to a closed pore structure after depressurization which is disadvantageous for 3D scaffolds as it does not fulfill the requirement of interconnectivity necessary for cell migration. To overcome these drawbacks, fibers forming macroporous structures were prepared using a semicontinuous antisolvent (SAS) technique.