Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 17;13(12):1982.
doi: 10.3390/polym13121982.

Supercritical Impregnation of Ketoprofen into Polylactic Acid for Biomedical Application: Analysis and Modeling of the Release Kinetic

Lidia Verano Naranjo  1 , Cristina Cejudo Bastante  1 , Lourdes Casas Cardoso  1 , Casimiro Mantell Serrano  1 , Enrique José Martínez de la Ossa Fernández  1
Affiliations

Supercritical Impregnation of Ketoprofen into Polylactic Acid for Biomedical Application: Analysis and Modeling of the Release Kinetic

Lidia Verano Naranjo et al. Polymers (Basel). .

Abstract

Ketoprofen (KET) is an anti-inflammatory drug often used in medicine due to its analgesic and antipyretic effects. If it is administered in a controlled form by means of different dosing devices, it acts throughout the patient's recovery period improving its efficacy. This study intends to support the use of supercritical solvent impregnation (SSI) as an efficient technique to develop polylactic acid (PLA) functionalized with ketoprofen, for use as controlled drug release devices. For this purpose, firstly, the influence of different SSI variables on the desirable swelling of the polymer structure, while avoiding their foaming, were evaluated. Then, the resulting ketoprofen loading was evaluated under different pressure/temperature conditions. It was generally found that as pressure and temperature are higher, the drug impregnation loads also increase. The maximum impregnation loads (at about 9% KET/PLA) were obtained at 200 bar and 75 °C. In vitro drug release tests of the impregnated compound were also carried out, and it was found that drug release profiles were also dependent on the specific pressure and temperature conditions used for the impregnation of each polymer filament.

Keywords: drug delivery implants; drug loading; drug release; ketoprofen; polylactic acid; supercritical solvent impregnation; swelling.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the supercritical solvent impregnation experiments.
Figure 2
Figure 2
Swelling of PLA filaments, (a) under CO2 in supercritical conditions, and (b) under scCO2-assisted impregnation with ketoprofen.
Figure 3
Figure 3
Standardized Pareto charts of the swelling of PLA filaments, (a) under CO2 supercritical conditions and (b) scCO2-assisted impregnation with ketoprofen.
Figure 4
Figure 4
Ketoprofen impregnation loading by SSI into PLA filaments: (a) total drug loading: percentage of impregnated ketoprofen respect to the amount of PLA, and (b) percentage of superficial drug respect to the total drug loaded.
Figure 5
Figure 5
Standardized Pareto chart of the (a) total ketoprofen loadings in PLA filaments and (b) percentage of superficial ketoprofen with respect to the total amount impregnated.
Figure 6
Figure 6
SEM images of (a) raw PLA filament (×1000), (b) PLA filament under scCO2 at 75 °C and 250 bar (×2400), (c) PLA filament impregnated with ketoprofen at 35 °C and 100 bar (×10,000), and (d) PLA filament impregnated with ketoprofen at 75 °C and 250 bar (×20,000). All are transversal sections of the polymer filaments.
Figure 7
Figure 7
Release profiles including the different phases of the release process from the PLA filaments impregnated with ketoprofen under different conditions.
Figure 8
Figure 8
Release profiles of the different ketoprofen-impregnated PLA filament samples fit to different mathematical models.
Figure 9
Figure 9
Fitting graphs of the ketoprofen-impregnated PLA filaments to the multiphasic power law model.
See this image and copyright information in PMC

References

    1. Davis S.S. Drug delivery systems. Interdiscip. Sci. Rev. 2000;25:175–183. doi: 10.1179/030801800679206. - DOI
    1. Braga M.E.M., Pato M.T.V., Silva H.S.R.C., Ferreira E.I., Gil M.H., Duarte C.M.M., de Sousa H.C. Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives. J. Supercrit. Fluids. 2008;44:245–257. doi: 10.1016/j.supflu.2007.10.002. - DOI
    1. Kazarian S.G. Polymer Processing with Supercritical Fluids. Polym. Sci. 2000;42:78–101.
    1. Yu J.P., Guan Y.X., Yao S.J., Zhu Z.Q. Preparation of roxithromycin-loaded poly(l-lactic acid) films with supercritical solution impregnation. Ind. Eng. Chem. Res. 2011;50:13813–13818. doi: 10.1021/ie201294u. - DOI
    1. Milovanovic S., Kuska R.M., Škorić-Lučić M.L., Kalagasidis-Krušić M.T., Frerich S., Žižović I.T., Ivanović J.Z. Swelling kinetics and impregnation of PLA with thymol under supercritical CO2 conditions. Tehnika. 2016;71:16–20. doi: 10.5937/tehnika1601016M. - DOI

LinkOut - more resources