(T1230-08-43) In Vitro Assessment of Cooling Potential of the Topical Gel System and Influence of Inactive Ingredients

Purpose: The purpose of the study was to explore an infrared thermal imaging (IRT)-based technique for in vitro assessment of the cooling potential of topical gel formulations containing hydroxyethyl cellulose (HEC), isopropyl alcohol (IPA), and propylene glycol (PG) at varying concentrations.

Methods: Twelve different gel formulations were prepared with various concentrations of HEC (1 to 5%), IPA (20-50%), and PG (15-50%) (Table 1). As shown in Figure 1, a piece of excised human skin was placed on a temperature-controlled plate maintained at 32 °C. 100 µL of each gel formulation stored at room temperature (24-25 °C) was dispensed and spread on the skin inside a rubber ring with 1.64 cm² area. The temperature dynamics of the area of interest were recorded at specific time intervals from 0 min (immediately after sample application) to 60 min of duration using IRT. Reference skin temperature (T_R≈32 °C) was recorded from a location where gels were not applied (red circular areas in Figure 1). The decrease in temperature following the application of gel was calculated by subtracting the temperature of gel (T_S) (blue circular area) values from the reference values (red circular areas). The temperature difference (ΔT=T_R-T_S) thus obtained was referred to as the cooling potential of the gel. The implied role of gel viscosity and solvent evaporation was understood through evaluating the correlation of ΔT with the zero-shear viscosity (η₀) and rate of evaporation (ROE) measured at 32 °C.

Results: The immediate ΔT (at t=0) of the formulations ranged from 5.44-8.95 °C (Table 2). The temperature differences elevated with the increase in HEC concentration, elucidating an enhancing cooling effect which showed a positive correlation with the viscosity (η₀). At constant HEC concentration, increasing IPA content from 20% to 50% demonstrated a consistent increase in ΔT of the gels. The gels with 20% and 30% PG had higher impact on decreasing the skin temperature compared to the gels with 40% and 50% PG. Over 60 minutes duration, the ΔT was reduced by up to 6.4 °C and based on the average data, the decline was maximum for IPA variants (5.75-6.4 °C) as compared to HEC (4.15-5 °C) and PG (4.55-5.35 °C) variants (Table 2). The IPA variants also showed relatively higher initial ROE (up to 10 min duration) which is likely to be a major contributing factor in induced cooling potential. With increasing HEC and PG concentrations, the ROE was greatly constrained throughout the 60 min period. After one hour, the ΔT for F04, F07, F08, F09, and F10 was sustained among the formulations. In low HEC and high PG variants, relatively low ΔT was ascribed to the potentially faster rate of thermal equilibration between the gels and the skin temperature due to lower gel viscosity.

Conclusion: The study highlights the use of IRT-based technique for in vitro assessment of cooling potential of the gel (measured as ΔT), following topical application on the skin. The evaluation of HEC gels showed that ΔT was greatly influenced by increase in the IPA concentrations, which is the most evaporative component in these formulations. The increase in concentration of the gelling agent, HEC, also showed enhancement of cooling potential, implying the significance of gel viscosity in thermal dynamics.

Acknowledgements: This project is supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award [U01FD006700] totaling $777,180 with 100 percent funded by FDA/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA, or the U.S. Government.


Figure 1. Illustration of in vitro study design to assess the temperature differences between reference skin temperature and sample gel temperature using infrared thermal imaging (IRT).


Table 1. Composition of hydroxyethyl cellulose (HEC) gel formulations.


Table 2. Temperature differences (ΔT=TR-TS) obtained through infrared thermal imaging at specified time points during 60 minutes of duration, and zero-shear viscosity (η0) of the formulations.