Salt-Stable LO Transdermal Studies
Study
Evaluation of the Percutaneous Absorption of Benzocaine + Lidocaine HCl +
Tetracaine HCl and Ketoprofen + Ibuprofen + Cyclobenzaprine HCl + Piroxicam,
In Vitro, Using the Epiderm Skin Model
The study was designed to evaluate the percutaneous absorption pharmacokinetics of
Humco’s Salt-Stable LO. Absorption was measured in human epidermal cultures, in
vitro, using the finite dose technique and Franz Diffusion Cells.
The two formulas were tested on standardized sections with three different transdermal
compounding bases, for the percutaneous absorption of Benzocaine + Lidocaine HCl +
Tetracaine HCl and Ketoprofen + Ibuprofen + Cyclobenzaprine HCl + Piroxicam over a
48-hour dose period. At pre-selected times after dose application, the dermal receptor
solution was removed in its entirety, replaced with fresh receptor solution, and an aliquot
saved for subsequent analysis. The samples were analyzed for Benzocaine, Lidocaine
HCl, Tetracaine HCl, Ketoprofen, Ibuprofen, Cyclobenzaprine HCl and Piroxicam
content by High Performance Liquid Chromatography (HPLC).
The in vitro human Epiderm skin model has proven to be a valuable tool for the study of
percutaneous absorption and the determination of the pharmacokinetics of topically
applied drugs. The model uses human epidermal skin mounted in specially designed
diffusion cells that allow the skin to be maintained at a temperature and humidity that
match typical in vitro conditions. A finite dose of formulation is applied to the outer
surface of the skin and drug absorption is measured by monitoring the rate of appearance
in the receptor solution bathing the inner surface of the skin. Data defining total
absorption, as well as rate of absorption can be accurately determined in this model.
Results
Benzocaine
The data indicate that Benzocaine did penetrate into and through human epidermal
cultures, in vitro, from the test formulations provided. The absorption profiles indicate a
rapid penetration to a peak flux occurring at approximately 12 hours after dose
application followed by a steady decline thereafter. Humco Salt-Stable LO performed
comparable to PCCA Lipoderm and significantly better than PLO at delivering
Benzocaine through human skin.
Benzocaine Flux vs. Time
Flux (ug/cm2/hr)
20.00
15.00
Salt-Stable LO
10.00
Lipoderm
PLO
5.00
0.00
0
12
24
36
48
Time (h)
Lidocaine HCl
The data indicate that Lidocaine HCl did penetrate into and through human epidermal
cultures, in vitro, from the test formulations provided. The absorption profiles indicate a
steady penetration to a peak flux occurring at approximately 36 hours after dose
application. Humco Salt-Stable LO performed significantly better than both PCCA
Lipoderm and PLO at delivering Lidocaine HCl through human skin.
Lidocaine HCl Flux vs. Time
Flux (ug/cm2/hr)
2.00
1.50
Salt-Stable LO
1.00
Lipoderm
PLO
0.50
0.00
0
12
24
Time (h)
36
48
Tetracaine HCl
The data indicate that Tetracaine HCl did penetrate into and through human epidermal
cultures, in vitro, from the test formulations provided. The absorption profiles indicate a
steady penetration to a peak flux occurring at approximately 36 hours after dose
application. Humco Salt-Stable LO performed significantly better than both PCCA
Lipoderm and PLO at delivering Tetracaine HCl through human skin.
Tetracaine HCl Flux vs. Time
Flux (ug/cm2/hr)
0.25
0.20
Salt-Stable LO
0.15
Lipoderm
0.10
PLO
0.05
0.00
0
12
24
36
48
Time (h)
Ketoprofen
The data indicate that Ketoprofen did penetrate into and through human epidermal
cultures, in vitro, from the test formulations provided. The absorption profiles indicate a
steady penetration to a peak flux occurring at approximately 36 hours after dose
application. Humco Salt-Stable LO performed comparable to both PCCA Lipoderm and
PLO at delivering Ketoprofen through human skin.
Ketoprofen Flux vs. Time
Flux (ug/cm2/hr)
3.00
2.50
2.00
Salt-Stable LO
1.50
Lipoderm
1.00
PLO
0.50
0.00
0
12
24
Time (h)
36
48
Ibuprofen
The data indicate that Ibuprofen did penetrate into and through human epidermal
cultures, in vitro, from the test formulations provided. The absorption profiles indicate a
rapid penetration to a peak flux occurring at approximately 12 hours after dose
application followed by a steady decline thereafter. Humco Salt-Stable LO performed
significantly better than both PCCA Lipoderm and PLO at delivering Ibuprofen through
human skin.
Flux (ug/cm2/hr)
Ibuprofen Flux vs. Time
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
Salt-Stable LO
Lipoderm
PLO
0
12
24
36
48
Time (h)
Cyclobenzaprine HCl
The data indicate that Cyclobenzaprine HCl did penetrate into and through human
epidermal cultures, in vitro, from the test formulations provided. The absorption profiles
indicate a steady penetration to a peak flux occurring at approximately 36 hours. Humco
Salt-Stable LO performed comparable to both PCCA Lipoderm and PLO at delivering
Cyclobenzaprine HCl through human skin.
Cyclobenzaprine HCl Flux vs. Time
Flux (ug/cm2/hr)
0.30
0.25
0.20
Salt-Stable LO
0.15
Lipoderm
0.10
PLO
0.05
0.00
0
12
24
Time (h)
36
48
Piroxicam
The data indicate that Piroxicam did penetrate into and through human epidermal
cultures, in vitro, from the test formulations provided. The absorption profiles indicate a
steady penetration to a peak flux occurring at approximately 36 hours. Humco Salt-Stable
LO performed comparable to both PCCA Lipoderm and PLO at delivering Piroxicam
through human skin.
Flux (ug/cm2/hr)
Piroxicam Flux vs. Time
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
Salt-Stable LO
Lipoderm
PLO
0
12
24
Time (h)
36
48
20% Benzocaine / 6% Lidocaine HCl / 4% Tetracaine HCl
The data indicate that the actives do penetrate into and through human epidermal
cultures. Based on total penetration (through the skin into the reservoir solution), the data
rank orders the test formulations as Humco Salt-Stable LO > PCCA Lipoderm > PLO.
Sample Chromatogram of 20% Benzocaine / 6% Lidocaine HCl / 4% Tetracaine HCl
Percent BLT Permeation Through the Stratum Corneum
120
100
100
100
Percent (%)
100
80
Salt-Stable LO
54
60
Lipoderm
PLO
40
20
8
8
8
4
0
0
Benzocaine
Lidocaine
Tetracaine
Active
The total percent of applied dose that penetrated past the Stratum Corneum with Humco
Salt-Stable LO was 45% more than PCCA Lipoderm and 50% more than PLO.
10% Ketoprofen / 10% Ibuprofen / 2% Cyclobenzaprine HCl / 2% Piroxicam
The data indicate that the actives do penetrate into and through human epidermal
cultures. Based on total penetration (through the skin into the reservoir solution), the data
rank orders the test formulations as Humco Salt-Stable LO = PCCA Lipoderm > PLO.
Sample Chromatograms of 10% Ketoprofen / 10% Ibuprofen / 2% Cyclobenzaprine HCl
/ 2% Piroxicam
Percent KICK Permeation Through the Stratum Corneum
45
39
40
Percent (%)
35
34
31
31
30
26
23
25
Salt-Stable LO
23
Lipoderm
20
16
15
16
PLO
10
8
10
5
5
0
Ketoprofen
Ibuprofen
Cyclobenzaprine
Piroxicam
Active
The total percent of applied dose that penetrated past the Stratum Corneum with Humco
Salt-Stable LO was comparable to PCCA Lipoderm and 37% more than PLO.