Comparison of Skin Permeation and Putative Anti-Inflammatory Activity of Commercially Available Topical Products Containing Ibuprofen and Diclofenac

Figures & data

Table 1 Qualitative Composition of Diclofenac and Ibuprofen Products as Labelled on the Packaging

Agent	API	Dosage Form	pH	Gelling Agent	Emulsifier	Emollients	Permeation Enhancer	pH Adjusting	Solvents/Cosolvents	Fragrance	Preservative
Diclo-1	Diclofenac DEA 2.32%	Emulsion	7.38	Carbomer	Macrogol cetostearyl ether	Liquid paraffin, Cocoyl caprylocaprate	Oleyl alcohol	DEA	Purified water, IPA, Propylene glycol	Perfume	BHT
Diclo-2	Diclofenac DEA 1.16%	Emulsion	7.25	Carbomer	Macrogol cetostearyl ether	Liquid paraffin, Cocoyl caprylocaprate	–	DEA	Purified water, IPA, Propylene glycol	Perfume	–
Diclo-3	Diclofenac DEA 1.16%	Emulsion	7.07	Carbomer	Polyoxyethylene alkyl ether	Liquid paraffin, Cocoyl caprylocaprate	–	DEA	Purified water, IPA, Propylene glycol	Fragrance	–
Diclo-4	Diclofenac DEA 1.16%	Emulsion	7.28	Carbomer	Macrogol 1000 monocetyl ether	Paraffin, Cocoyl caprylocaprate	–	DEA	Water, IPA, Propylene glycol	Lavandula officinalis flower oil	–
Diclo-5	Diclofenac DEA 1.16%	Gel	7.13	Carbomer	–	–	–	Triethanolamine	Water, Ethanol	Lavandula angustifolia flower	Methylparaben
Diclo-6	Diclofenac sodium 1%	Gel	7.86	Carbomer	–	–	–	Ammonium solution	Purified water, IPA, Ethanol	–	–
Ibu-1	Ibuprofen 5%	Cream	6.17	Xanthan gum	Macrogol stearate 30 and 100	Glyceryl monostearate, Medium chain triglyceride	Propylene glycol	–	–	Lavender and orange blossom	–
Ibu-2	Ibuprofen 5%	Cream	5.94	Xanthan gum	Macrogol stearate 1500 and 5000	Glyceryl monostearate, Medium chain triglyceride	Propylene glycol	–	Purified water	Bitter orange blossoms, lavender oil	Methyl 4-hydroxybenzoate sodium
Ibu-3	Ibuprofen 5%	Gel	4.64	Poloxamer	–	Medium chain triglyceride	–	–	Purified water, IPA, Glycerol dimethyl ketal	Bitter orange blossoms, lavender oil	–
Ibu-4	Ibuprofen 5%	Gel	4.79	Poloxamer	–	Medium chain triglyceride	–	–	Purified water, IPA, Dimethyl isosorbide	Bitter orange blossoms, lavender oil	–
Ibu-5	Ibuprofen 10%	Gel	7.76	HEC	–	–	–	Sodium hydroxide	Purified water, IPA, Benzyl alcohol	–	–
Ibu-6	Ibuprofen 10%	Gel	6.84	Carbomer	–	–	–	DEA	Purified water, Industrial methylated spirit	–	–

Abbreviations: API, active pharmaceutical ingredient; BHT, butylhydroxytoluene; DEA, diethylamine; HEC, hydroxyethylcellulose; IPA, isopropyl alcohol.

Figure 1 Cumulative absorption at 24h of topical diclofenac and ibuprofen products (geometric means and 95% confidence intervals).

Table 2 Ratios (95% CIs) of Adjusted Geometric Means of Cumulative Absorption at 24h for Diclofenac and Ibuprofen Formulations

Diclofenac Formulations
	vs Diclo-1	vs Diclo-2	vs Diclo-3	vs Diclo-4	vs Diclo-5	vs Diclo-6
Diclo-1	–	4.06 (2.54–6.50)	2.54 (1.59–4.07)	3.67 (2.29–5.88)	7.13 (4.46–11.42)	1.14 (0.71–1.82)
Diclo-2	0.25 (0.15–0.39)	–	0.63 (0.39–1.00)	0.91 (0.57–1.45)	1.76 (1.10–2.81)	0.28 (0.18–0.45)
Diclo-3	0.39 (0.25–0.63)	1.60 (1.00–2.55)	–	1.44 (0.90–2.31)	2.80 (1.75–4.49)	0.45 (0.28–0.72)
Diclo-4	0.27 (0.17–0.44)	1.10 (0.69–1.77)	0.69 (0.43–1.11)	–	1.94 (1.21–3.11)	0.31 (0.19–0.50)
Diclo-5	0.14 (0.09–0.22)	0.57 (0.36–0.91)	0.36 (0.22–0.57)	0.51 (0.32–0.82)	–	0.16 (0.10–0.26)
Diclo-6	0.88 (0.55–1.41)	3.57 (2.23–5.71)	2.24 (1.40–3.58)	3.23 (2.02–5.17)	6.27 (3.92–10.04)	–
Ibuprofen Formulations
	vs Ibu-1	vs Ibu-2	vs Ibu-3	vs Ibu-4	vs Ibu-5	vs Ibu-6
Ibu-1	–	1.11 (0.85–1.45)	1.44 (1.10–1.88)	1.56 (1.20–2.04)	0.60 (0.46–0.79)	0.37 (0.28–0.48)
Ibu-2	0.90 (0.69–1.17)	–	1.29 (0.99–1.69)	1.40 (1.08–1.83)	0.54 (0.42–0.71)	0.33 (0.25–0.43)
Ibu-3	0.69 (0.53–0.91)	0.77 (0.59–1.01)	–	1.09 (0.83–1.42)	0.42 (0.32–0.55)	0.26 (0.20–0.33)
Ibu-4	0.64 (0.49–0.83)	0.71 (0.55–0.93)	0.92 (0.71–1.20)	–	0.39 (0.30–0.50)	0.24 (0.18–0.31)
Ibu-5	1.66 (1.27–2.16)	1.85 (1.42–2.41)	2.39 (1.83–3.12)	2.59 (1.99–3.38)	–	0.61 (0.47–0.80)
Ibu-6	2.72 (2.09–3.55)	3.03 (2.32–3.95)	3.92 (3.01–5.11)	4.25 (3.26–5.55)	1.64 (1.26–2.14)	–

Figure 2 Median fluxes of topical diclofenac (A) and ibuprofen (B) products.

Figure 3 Modified index of anti-inflammatory activity for topical diclofenac and ibuprofen products.