Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices

Chiara Mazzoni*, Fabio Tentor, Anastasia Antalaki, Rasmus D. Jacobsen, Jacob Mortensen, Roman Slipets, Oleksii Ilchenko, Stephan S. Keller, L. Hagner Nielsen, Anja Boisen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

To enhance oral bioavailability of poorly soluble drugs, microfabricated devices can be utilized. One example of such devices is microcontainers. These are cylindrical in shape with an inner cavity for drug loading and with only the top side open for release. Supercritical CO2 (scCO2) impregnation is an interesting technique for loading drugs into polymeric matrices in, for example, microcontainers since it avoids the use of organic solvents and is cheap. One of the main drawbacks of this technique is the unknown three-dimensional drug distribution in the polymer matrix. The aim of this study was to investigate the loading of two poorly soluble drugs, naproxen and ketoprofen, by scCO2 impregnation into confined polymermatrices of different sizes. Three different sizes of microcontainers (small, medium, and large) and, thereby, different surface areas accessible for impregnation were compared. From in vitro studies, the amount of naproxen and ketoprofen loaded into the different microcontainers and their corresponding release profiles were seen to be similar. A custom-made Raman microscope facilitated volumetric Raman maps of an entire microcontainer filled with polyvinylpyrrolidone (PVP) and scCO2 impregnated with either naproxen or ketoprofen. In all microcontainer sizes, the drugs were only detected in the top layer of the polymer matrix, explaining the observed similar release profiles. Using X-ray powder diffraction and Raman spectroscopy, the solid state form of the drugs was evaluated, showing that ketoprofen was amorphous in all microcontainer sizes. Naproxen was found not to be crystalline nor amorphous but in a less ordered configuration than the crystalline state. In conclusion, volumetric Raman mapping is a powerful technology for imaging drug distribution and drug crystallinity in polymers and allowed us to conclude that (i) scCO2 impregnation depth does not depend on surface area and (ii) impregnated drugs are noncrystalline.
Original languageEnglish
JournalA C S Biomaterials Science & Engineering
Volume5
Issue number6
Pages (from-to)2935-2941
ISSN2373-9878
DOIs
Publication statusPublished - 2019

Keywords

  • Microdevices
  • Polymer matrix
  • Drug distribution
  • Poorly soluble drug
  • Supercritical CO2 impregnation
  • Raman spectroscopy

Cite this

@article{e64e7f9708db4748a7f11e72c83093f7,
title = "Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices",
abstract = "To enhance oral bioavailability of poorly soluble drugs, microfabricated devices can be utilized. One example of such devices is microcontainers. These are cylindrical in shape with an inner cavity for drug loading and with only the top side open for release. Supercritical CO2 (scCO2) impregnation is an interesting technique for loading drugs into polymeric matrices in, for example, microcontainers since it avoids the use of organic solvents and is cheap. One of the main drawbacks of this technique is the unknown three-dimensional drug distribution in the polymer matrix. The aim of this study was to investigate the loading of two poorly soluble drugs, naproxen and ketoprofen, by scCO2 impregnation into confined polymermatrices of different sizes. Three different sizes of microcontainers (small, medium, and large) and, thereby, different surface areas accessible for impregnation were compared. From in vitro studies, the amount of naproxen and ketoprofen loaded into the different microcontainers and their corresponding release profiles were seen to be similar. A custom-made Raman microscope facilitated volumetric Raman maps of an entire microcontainer filled with polyvinylpyrrolidone (PVP) and scCO2 impregnated with either naproxen or ketoprofen. In all microcontainer sizes, the drugs were only detected in the top layer of the polymer matrix, explaining the observed similar release profiles. Using X-ray powder diffraction and Raman spectroscopy, the solid state form of the drugs was evaluated, showing that ketoprofen was amorphous in all microcontainer sizes. Naproxen was found not to be crystalline nor amorphous but in a less ordered configuration than the crystalline state. In conclusion, volumetric Raman mapping is a powerful technology for imaging drug distribution and drug crystallinity in polymers and allowed us to conclude that (i) scCO2 impregnation depth does not depend on surface area and (ii) impregnated drugs are noncrystalline.",
keywords = "Microdevices, Polymer matrix, Drug distribution, Poorly soluble drug, Supercritical CO2 impregnation, Raman spectroscopy",
author = "Chiara Mazzoni and Fabio Tentor and Anastasia Antalaki and Jacobsen, {Rasmus D.} and Jacob Mortensen and Roman Slipets and Oleksii Ilchenko and Keller, {Stephan S.} and Nielsen, {L. Hagner} and Anja Boisen",
year = "2019",
doi = "10.1021/acsbiomaterials.9b00495",
language = "English",
volume = "5",
pages = "2935--2941",
journal = "A C S Biomaterials Science & Engineering",
issn = "2373-9878",
publisher = "American Chemical Society",
number = "6",

}

Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices. / Mazzoni, Chiara; Tentor, Fabio; Antalaki, Anastasia; Jacobsen, Rasmus D.; Mortensen, Jacob; Slipets, Roman; Ilchenko, Oleksii; Keller, Stephan S.; Nielsen, L. Hagner; Boisen, Anja.

In: A C S Biomaterials Science & Engineering, Vol. 5, No. 6, 2019, p. 2935-2941.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices

AU - Mazzoni, Chiara

AU - Tentor, Fabio

AU - Antalaki, Anastasia

AU - Jacobsen, Rasmus D.

AU - Mortensen, Jacob

AU - Slipets, Roman

AU - Ilchenko, Oleksii

AU - Keller, Stephan S.

AU - Nielsen, L. Hagner

AU - Boisen, Anja

PY - 2019

Y1 - 2019

N2 - To enhance oral bioavailability of poorly soluble drugs, microfabricated devices can be utilized. One example of such devices is microcontainers. These are cylindrical in shape with an inner cavity for drug loading and with only the top side open for release. Supercritical CO2 (scCO2) impregnation is an interesting technique for loading drugs into polymeric matrices in, for example, microcontainers since it avoids the use of organic solvents and is cheap. One of the main drawbacks of this technique is the unknown three-dimensional drug distribution in the polymer matrix. The aim of this study was to investigate the loading of two poorly soluble drugs, naproxen and ketoprofen, by scCO2 impregnation into confined polymermatrices of different sizes. Three different sizes of microcontainers (small, medium, and large) and, thereby, different surface areas accessible for impregnation were compared. From in vitro studies, the amount of naproxen and ketoprofen loaded into the different microcontainers and their corresponding release profiles were seen to be similar. A custom-made Raman microscope facilitated volumetric Raman maps of an entire microcontainer filled with polyvinylpyrrolidone (PVP) and scCO2 impregnated with either naproxen or ketoprofen. In all microcontainer sizes, the drugs were only detected in the top layer of the polymer matrix, explaining the observed similar release profiles. Using X-ray powder diffraction and Raman spectroscopy, the solid state form of the drugs was evaluated, showing that ketoprofen was amorphous in all microcontainer sizes. Naproxen was found not to be crystalline nor amorphous but in a less ordered configuration than the crystalline state. In conclusion, volumetric Raman mapping is a powerful technology for imaging drug distribution and drug crystallinity in polymers and allowed us to conclude that (i) scCO2 impregnation depth does not depend on surface area and (ii) impregnated drugs are noncrystalline.

AB - To enhance oral bioavailability of poorly soluble drugs, microfabricated devices can be utilized. One example of such devices is microcontainers. These are cylindrical in shape with an inner cavity for drug loading and with only the top side open for release. Supercritical CO2 (scCO2) impregnation is an interesting technique for loading drugs into polymeric matrices in, for example, microcontainers since it avoids the use of organic solvents and is cheap. One of the main drawbacks of this technique is the unknown three-dimensional drug distribution in the polymer matrix. The aim of this study was to investigate the loading of two poorly soluble drugs, naproxen and ketoprofen, by scCO2 impregnation into confined polymermatrices of different sizes. Three different sizes of microcontainers (small, medium, and large) and, thereby, different surface areas accessible for impregnation were compared. From in vitro studies, the amount of naproxen and ketoprofen loaded into the different microcontainers and their corresponding release profiles were seen to be similar. A custom-made Raman microscope facilitated volumetric Raman maps of an entire microcontainer filled with polyvinylpyrrolidone (PVP) and scCO2 impregnated with either naproxen or ketoprofen. In all microcontainer sizes, the drugs were only detected in the top layer of the polymer matrix, explaining the observed similar release profiles. Using X-ray powder diffraction and Raman spectroscopy, the solid state form of the drugs was evaluated, showing that ketoprofen was amorphous in all microcontainer sizes. Naproxen was found not to be crystalline nor amorphous but in a less ordered configuration than the crystalline state. In conclusion, volumetric Raman mapping is a powerful technology for imaging drug distribution and drug crystallinity in polymers and allowed us to conclude that (i) scCO2 impregnation depth does not depend on surface area and (ii) impregnated drugs are noncrystalline.

KW - Microdevices

KW - Polymer matrix

KW - Drug distribution

KW - Poorly soluble drug

KW - Supercritical CO2 impregnation

KW - Raman spectroscopy

U2 - 10.1021/acsbiomaterials.9b00495

DO - 10.1021/acsbiomaterials.9b00495

M3 - Journal article

VL - 5

SP - 2935

EP - 2941

JO - A C S Biomaterials Science & Engineering

JF - A C S Biomaterials Science & Engineering

SN - 2373-9878

IS - 6

ER -