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Effect of Salt Form on Gelation and Drug Delivery Properties of Diclofenac-Loaded Poloxamer Gels for Delivery to Impaired Skin

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Abstract

Purpose

Treating chronic wounds is a significant clinical challenge, and a topical product would be ideal for pain management. Poloxamer 407, a thermosensitive polymer, would allow an analgesic drug to be topically applied to a wound as a liquid that transitions to a gel at physiologic temperature. Using diclofenac as a model analgesic drug, our goal was to determine effects of salt form on poloxamer gelation and drug delivery from poloxamer gels applied to excised skin with impaired barrier function.

Methods

Gelation properties of 17% and 20% poloxamer gels loaded with 0.4 to 1.7% diclofenac sodium, potassium, epolamine, or diethylamine were evaluated rheologically. Drug release and delivery were quantified using cellulose membranes, porcine skin, and tape-stripped porcine skin.

Results

Poloxamer gelation temperature increased with higher diclofenac concentration, regardless of salt form; the magnitude of increase varied in the following order: sodium>potassium>diethylamine>epolamine. Gelation temperature differences resulting from the various counterions generally matched previously observed trends of ion-specific effects on macromolecule solubility (the Hofmeister series). Despite changes in gelation behavior, we observed minimal corresponding effects on drug release or delivery. There were no significant differences in diclofenac released or delivered through intact porcine skin over 48 h. However, in studies with impaired (tape-stripped) skin, diclofenac delivery was slowest overall with the epolamine salt.

Conclusion

Varying the salt form of a model analgesic drug can impact gelation and drug delivery characteristics of poloxamer systems. Further study of the mechanisms of these changes will be important for continued development of topical poloxamer products for clinical wound care.

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Data Availability

All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by a training fellowship from the University of Iowa Center for Biocatalysis and Bioprocessing and the NIH-Sponsored Predoctoral Training Program in Biotechnology (T32 GM008365). This work was also supported by the National Institute of General Medical Sciences under award R35GM124551.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA, 52242, USA

    Jackson Russo & Nicole K. Brogden

  2. The University of Iowa College of Pharmacy, 180 S. Grand Ave, Iowa City, IA, 52242, USA

    Jackson Russo & Nicole K. Brogden

  3. Department of Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA, 52242, USA

    Jennifer Fiegel

  4. Department of Dermatology, The University of Iowa, Iowa City, IA, 52242, USA

    Nicole K. Brogden

Authors
  1. Jackson Russo
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  2. Jennifer Fiegel
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Contributions

JR: Conceptualization, investigation, formal analysis, writing original draft.

JF: Conceptualization, formal analysis, editing and review.

NKB: Conceptualization, formal analysis, writing original draft, editing and review.

Corresponding author

Correspondence to Nicole K. Brogden.

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Russo, J., Fiegel, J. & Brogden, N.K. Effect of Salt Form on Gelation and Drug Delivery Properties of Diclofenac-Loaded Poloxamer Gels for Delivery to Impaired Skin. Pharm Res 39, 2515–2527 (2022). https://doi.org/10.1007/s11095-022-03356-1

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