Evaluation of the Physicochemical and Biopharmaceutical properties of Fluoro-Indomethacin

Michela M. Mori, Anu J. Airaksinen, Jouni T. Hirvonen, Hélder A. Santos, Carla M. Caramella

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Drug nanocarriers have shown great potential in therapy and as diagnostic probes, such as in imaging of cancer and inflammation. Imaging can be applied to localize the carrier or the drug itself in the body and/or tissues. In this particular case it is important that drug molecules have the characteristics for possible detection, e.g. after modification with positron emission tomography (PET) compliant radioisotopes, without affecting their pharmacological behaviour. In order to easily and efficiently follow the ADME profile of the drug after loaded into nanocarriers, the drug can be radiolabelled with, e.g. 18F-label, in order to assess its biodistribution after enteral and parenteral administration in rats. However, this is only possible if the derivative compound behaves similarly to the parent drug compound. In this study, indomethacin (a poorly water-soluble drug) was chosen as a model compound and aimed to evaluate the physicochemical and biopharmaceutical properties of an analogue of indomethacin (IMC), fluoro-indomethacin (F-IMC). Although some of the physicochemical and biopharmaceutical properties of IMC are already known, in order to establish a feasible comparison between IMC and F-IMC, the behaviour of the former was also investigated in the same conditions as for F-IMC. In this context, both IMC and F-IMC were thermally and morphologically studied. Furthermore, the following properties were also studied for both compounds: pKa and log P, solubility and dissolution profiles at physiological pH values, and toxicity at different concentrations in Caco-2 cells. Finally, the transport across Caco-2 monolayers of the IMC and F-IMC at physiological pH range was also investigated. The results obtained showed similar values in pKa-logP, solubility, dissolution, cytotoxicity, and permeability for both compounds. Thus, there might be strong evidence that both IMC and F-IMC should have a similar ADME behaviour and profiles in vivo. The results provide fundamental tools and ideas for further research with nanocarriers of 18F-IMC.
Original languageEnglish
JournalCurrent Drug Metabolism
Volume14
Issue number1
Pages (from-to)80-89
Number of pages9
ISSN1389-2002
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy

Cite this

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abstract = "Drug nanocarriers have shown great potential in therapy and as diagnostic probes, such as in imaging of cancer and inflammation. Imaging can be applied to localize the carrier or the drug itself in the body and/or tissues. In this particular case it is important that drug molecules have the characteristics for possible detection, e.g. after modification with positron emission tomography (PET) compliant radioisotopes, without affecting their pharmacological behaviour. In order to easily and efficiently follow the ADME profile of the drug after loaded into nanocarriers, the drug can be radiolabelled with, e.g. 18F-label, in order to assess its biodistribution after enteral and parenteral administration in rats. However, this is only possible if the derivative compound behaves similarly to the parent drug compound. In this study, indomethacin (a poorly water-soluble drug) was chosen as a model compound and aimed to evaluate the physicochemical and biopharmaceutical properties of an analogue of indomethacin (IMC), fluoro-indomethacin (F-IMC). Although some of the physicochemical and biopharmaceutical properties of IMC are already known, in order to establish a feasible comparison between IMC and F-IMC, the behaviour of the former was also investigated in the same conditions as for F-IMC. In this context, both IMC and F-IMC were thermally and morphologically studied. Furthermore, the following properties were also studied for both compounds: pKa and log P, solubility and dissolution profiles at physiological pH values, and toxicity at different concentrations in Caco-2 cells. Finally, the transport across Caco-2 monolayers of the IMC and F-IMC at physiological pH range was also investigated. The results obtained showed similar values in pKa-logP, solubility, dissolution, cytotoxicity, and permeability for both compounds. Thus, there might be strong evidence that both IMC and F-IMC should have a similar ADME behaviour and profiles in vivo. The results provide fundamental tools and ideas for further research with nanocarriers of 18F-IMC.",
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author = "Mori, {Michela M.} and Airaksinen, {Anu J.} and Hirvonen, {Jouni T.} and {A. Santos}, H{\'e}lder and Caramella, {Carla M.}",
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Evaluation of the Physicochemical and Biopharmaceutical properties of Fluoro-Indomethacin. / Mori, Michela M.; Airaksinen, Anu J.; Hirvonen, Jouni T.; A. Santos, Hélder; Caramella, Carla M.

In: Current Drug Metabolism, Vol. 14, No. 1, 2013, p. 80-89.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Evaluation of the Physicochemical and Biopharmaceutical properties of Fluoro-Indomethacin

AU - Mori, Michela M.

AU - Airaksinen, Anu J.

AU - Hirvonen, Jouni T.

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AU - Caramella, Carla M.

PY - 2013

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N2 - Drug nanocarriers have shown great potential in therapy and as diagnostic probes, such as in imaging of cancer and inflammation. Imaging can be applied to localize the carrier or the drug itself in the body and/or tissues. In this particular case it is important that drug molecules have the characteristics for possible detection, e.g. after modification with positron emission tomography (PET) compliant radioisotopes, without affecting their pharmacological behaviour. In order to easily and efficiently follow the ADME profile of the drug after loaded into nanocarriers, the drug can be radiolabelled with, e.g. 18F-label, in order to assess its biodistribution after enteral and parenteral administration in rats. However, this is only possible if the derivative compound behaves similarly to the parent drug compound. In this study, indomethacin (a poorly water-soluble drug) was chosen as a model compound and aimed to evaluate the physicochemical and biopharmaceutical properties of an analogue of indomethacin (IMC), fluoro-indomethacin (F-IMC). Although some of the physicochemical and biopharmaceutical properties of IMC are already known, in order to establish a feasible comparison between IMC and F-IMC, the behaviour of the former was also investigated in the same conditions as for F-IMC. In this context, both IMC and F-IMC were thermally and morphologically studied. Furthermore, the following properties were also studied for both compounds: pKa and log P, solubility and dissolution profiles at physiological pH values, and toxicity at different concentrations in Caco-2 cells. Finally, the transport across Caco-2 monolayers of the IMC and F-IMC at physiological pH range was also investigated. The results obtained showed similar values in pKa-logP, solubility, dissolution, cytotoxicity, and permeability for both compounds. Thus, there might be strong evidence that both IMC and F-IMC should have a similar ADME behaviour and profiles in vivo. The results provide fundamental tools and ideas for further research with nanocarriers of 18F-IMC.

AB - Drug nanocarriers have shown great potential in therapy and as diagnostic probes, such as in imaging of cancer and inflammation. Imaging can be applied to localize the carrier or the drug itself in the body and/or tissues. In this particular case it is important that drug molecules have the characteristics for possible detection, e.g. after modification with positron emission tomography (PET) compliant radioisotopes, without affecting their pharmacological behaviour. In order to easily and efficiently follow the ADME profile of the drug after loaded into nanocarriers, the drug can be radiolabelled with, e.g. 18F-label, in order to assess its biodistribution after enteral and parenteral administration in rats. However, this is only possible if the derivative compound behaves similarly to the parent drug compound. In this study, indomethacin (a poorly water-soluble drug) was chosen as a model compound and aimed to evaluate the physicochemical and biopharmaceutical properties of an analogue of indomethacin (IMC), fluoro-indomethacin (F-IMC). Although some of the physicochemical and biopharmaceutical properties of IMC are already known, in order to establish a feasible comparison between IMC and F-IMC, the behaviour of the former was also investigated in the same conditions as for F-IMC. In this context, both IMC and F-IMC were thermally and morphologically studied. Furthermore, the following properties were also studied for both compounds: pKa and log P, solubility and dissolution profiles at physiological pH values, and toxicity at different concentrations in Caco-2 cells. Finally, the transport across Caco-2 monolayers of the IMC and F-IMC at physiological pH range was also investigated. The results obtained showed similar values in pKa-logP, solubility, dissolution, cytotoxicity, and permeability for both compounds. Thus, there might be strong evidence that both IMC and F-IMC should have a similar ADME behaviour and profiles in vivo. The results provide fundamental tools and ideas for further research with nanocarriers of 18F-IMC.

KW - 317 Pharmacy

U2 - 10.2174/138920013804545179

DO - 10.2174/138920013804545179

M3 - Article

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SP - 80

EP - 89

JO - Current Drug Metabolism

JF - Current Drug Metabolism

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