A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection. / Thing, Mette; Agårdh, Li; Larsen, Susan; Rasmussen, Rune; Pallesen, Jakob; Mertz, Nina; Kristensen, Jesper Langgaard; Hansen, Martin; Ostergaard, Jesper; Larsen, Claus Selch.

In: Journal of Pharmaceutical Sciences, Vol. 103, No. 12, 2014, p. 4021–4029.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Thing, M, Agårdh, L, Larsen, S, Rasmussen, R, Pallesen, J, Mertz, N, Kristensen, JL, Hansen, M, Ostergaard, J & Larsen, CS 2014, 'A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection', Journal of Pharmaceutical Sciences, vol. 103, no. 12, pp. 4021–4029. https://doi.org/10.1002/jps.24221

APA

Thing, M., Agårdh, L., Larsen, S., Rasmussen, R., Pallesen, J., Mertz, N., Kristensen, J. L., Hansen, M., Ostergaard, J., & Larsen, C. S. (2014). A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection. Journal of Pharmaceutical Sciences, 103(12), 4021–4029. https://doi.org/10.1002/jps.24221

Vancouver

Thing M, Agårdh L, Larsen S, Rasmussen R, Pallesen J, Mertz N et al. A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection. Journal of Pharmaceutical Sciences. 2014;103(12):4021–4029. https://doi.org/10.1002/jps.24221

Author

Thing, Mette ; Agårdh, Li ; Larsen, Susan ; Rasmussen, Rune ; Pallesen, Jakob ; Mertz, Nina ; Kristensen, Jesper Langgaard ; Hansen, Martin ; Ostergaard, Jesper ; Larsen, Claus Selch. / A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection. In: Journal of Pharmaceutical Sciences. 2014 ; Vol. 103, No. 12. pp. 4021–4029.

Bibtex

@article{fa0be569d9a44db1bed6b970b618dd8b,
title = "A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection",
abstract = "Long-acting nonsteroidal anti-inflammatory drug formulations for intra-articular injection might be effective in the management of joint pain and inflammation associated sports injuries and osteoarthritis. In this study, a prodrug-based delivery system was evaluated. The synthesized diclofenac ester prodrug, a weak base (pKa 7.52), has relatively high solubility at low pH (6.5 mg mL(-1) at pH 4) and much lower solubility at physiological pH (4.5 μg mL(-1) at pH 7.4) at 37°C. In biological media including 80% (v/v) human synovial fluid (SF), the prodrug was cleaved to diclofenac mediated by esterases. In situ precipitation of the prodrug was observed upon addition of a concentrated slightly acidic prodrug solution to phosphate buffer or SF at pH 7.4. The degree of supersaturation accompanying the precipitation process was more pronounced in SF than in phosphate buffer. In the rotating dialysis cell model, a slightly acidic prodrug solution was added to the donor cell containing 80% SF resulting in a continuous appearance of diclofenac in the acceptor phase for more than 43 h after an initial lag period of 8 h. Detectable amounts of prodrug were found in the rat joint up to 8 days after knee injection of the acidic prodrug solution. {\textcopyright} 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.",
author = "Mette Thing and Li Ag{\aa}rdh and Susan Larsen and Rune Rasmussen and Jakob Pallesen and Nina Mertz and Kristensen, {Jesper Langgaard} and Martin Hansen and Jesper Ostergaard and Larsen, {Claus Selch}",
note = "{\textcopyright} 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.",
year = "2014",
doi = "10.1002/jps.24221",
language = "English",
volume = "103",
pages = "4021–4029",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier",
number = "12",

}

RIS

TY - JOUR

T1 - A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection

AU - Thing, Mette

AU - Agårdh, Li

AU - Larsen, Susan

AU - Rasmussen, Rune

AU - Pallesen, Jakob

AU - Mertz, Nina

AU - Kristensen, Jesper Langgaard

AU - Hansen, Martin

AU - Ostergaard, Jesper

AU - Larsen, Claus Selch

N1 - © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

PY - 2014

Y1 - 2014

N2 - Long-acting nonsteroidal anti-inflammatory drug formulations for intra-articular injection might be effective in the management of joint pain and inflammation associated sports injuries and osteoarthritis. In this study, a prodrug-based delivery system was evaluated. The synthesized diclofenac ester prodrug, a weak base (pKa 7.52), has relatively high solubility at low pH (6.5 mg mL(-1) at pH 4) and much lower solubility at physiological pH (4.5 μg mL(-1) at pH 7.4) at 37°C. In biological media including 80% (v/v) human synovial fluid (SF), the prodrug was cleaved to diclofenac mediated by esterases. In situ precipitation of the prodrug was observed upon addition of a concentrated slightly acidic prodrug solution to phosphate buffer or SF at pH 7.4. The degree of supersaturation accompanying the precipitation process was more pronounced in SF than in phosphate buffer. In the rotating dialysis cell model, a slightly acidic prodrug solution was added to the donor cell containing 80% SF resulting in a continuous appearance of diclofenac in the acceptor phase for more than 43 h after an initial lag period of 8 h. Detectable amounts of prodrug were found in the rat joint up to 8 days after knee injection of the acidic prodrug solution. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

AB - Long-acting nonsteroidal anti-inflammatory drug formulations for intra-articular injection might be effective in the management of joint pain and inflammation associated sports injuries and osteoarthritis. In this study, a prodrug-based delivery system was evaluated. The synthesized diclofenac ester prodrug, a weak base (pKa 7.52), has relatively high solubility at low pH (6.5 mg mL(-1) at pH 4) and much lower solubility at physiological pH (4.5 μg mL(-1) at pH 7.4) at 37°C. In biological media including 80% (v/v) human synovial fluid (SF), the prodrug was cleaved to diclofenac mediated by esterases. In situ precipitation of the prodrug was observed upon addition of a concentrated slightly acidic prodrug solution to phosphate buffer or SF at pH 7.4. The degree of supersaturation accompanying the precipitation process was more pronounced in SF than in phosphate buffer. In the rotating dialysis cell model, a slightly acidic prodrug solution was added to the donor cell containing 80% SF resulting in a continuous appearance of diclofenac in the acceptor phase for more than 43 h after an initial lag period of 8 h. Detectable amounts of prodrug were found in the rat joint up to 8 days after knee injection of the acidic prodrug solution. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

U2 - 10.1002/jps.24221

DO - 10.1002/jps.24221

M3 - Journal article

C2 - 25354787

VL - 103

SP - 4021

EP - 4029

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 12

ER -

ID: 126172627