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. 2020 Dec 15;12(12):1214.
doi: 10.3390/pharmaceutics12121214.

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

Jackson Russo  1 , Jennifer Fiegel  2 , Nicole K Brogden  1   3
Affiliations

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

Jackson Russo et al. Pharmaceutics. .

Abstract

Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site.

Keywords: analgesia; chronic wounds; poloxamer; thermogelation; topical.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Solution of 20% w/w poloxamer 407 in water (A) at 4 °C prior to heating and (B) after heating on a stir plate until gelation occurred, causing the stir bar to stop moving.
Figure 2
Figure 2
Strain sweeps for 17% (A) and 20% w/w (B) poloxamer gels at 37 °C. Sweeps were conducted over an oscillation strain range from 0.1 to 100%. The approximate linear viscoelastic region of each formulation is boxed. An oscillation strain of 0.2% was chosen from the two linear viscoelastic regions for use in further poloxamer rheology studies.
Figure 3
Figure 3
Temperature sweeps from 14 to 38 °C for 17% (filled circles) and 20% (open circles) w/w poloxamer 407 solutions without (A) and with (B,C) 0–2% diclofenac sodium. Data are presented as mean ± SD (n = 3). SD error bars are omitted for figure clarity in panels (B,C).
Figure 4
Figure 4
Gelation temperatures for 17% (circles) or 20% w/w (open squares) poloxamer 407 solutions containing between 0% and 2% w/v diclofenac sodium. The dashed line represents approximate room temperature of 23 °C, which was chosen as the minimum preferred gelation temperature to prevent premature gelation. The solid line represents approximate minimum wound temperature of 30 °C [34]. Data are presented as mean ± SD (n = 3). Error bars for most conditions are too small to be seen in the figure.
Figure 5
Figure 5
In vitro drug release study using a Snakeskin® dialysis membrane. (A) Percent of the initial 5 mg dose released from each formulation over 24 h. (B) Total mass of diclofenac sodium released from each formulation over 24 h. Data presented as mean ± SD (n = 3). ** p ≤ 0.01.
Figure 6
Figure 6
In vitro drug permeation study through intact porcine ear skin. (A) Percent of the initial 5 mg dose delivered to the receiver compartment over 24 h. (B) Total mass of diclofenac sodium delivered to the receiver compartment over 24 h. (C) Total mass of diclofenac sodium extracted per gram of skin upon completion of 24-h permeation study. Data presented as mean ± SD (n = 3 for all treatment conditions except solution in water, for which n = 6). ** p ≤ 0.01.
Figure 7
Figure 7
Transepidermal water loss (TEWL) results after tape stripping of skin samples used for the permeation testing in impaired skin samples. The X axis shows what diclofenac formulation was applied to those impaired skin samples. Number of tape strips used varied between samples (described in Methods Section). Data presented as mean ± SD (n = 3). ** p < 0.01, *** p < 0.001, **** p < 0.0001.
Figure 8
Figure 8
In vitro drug permeation study using porcine ear skin impaired via tape stripping. (A) % of the initial 5 mg dose delivered to the receiver compartment over 24 h. (B) Total mass of diclofenac sodium delivered to the receiver compartment over 24 h. (C) Total mass of diclofenac sodium extracted from skin upon completion of 24-h permeation study. Data presented as mean ± SD (n = 3). ** p ≤ 0.01, **** p ≤ 0.0001.
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