In Vitro Rheology Predicts Improved Spreadability of Tazarotene 0.045% Lotion Versus Trifarotene 0.005% Cream
March 2022 | Volume 21 | Issue 3 | Original Article | 250 | Copyright © March 2022
Published online February 24, 2022
Zoe D. Draelos MD,a Emil A. Tanghetti MD,b William Philip Werschler MD,c Leon H. Kircik MD,d,e,f Arturo Angel BS,g Earl Lagmay BS,g Eric Guenin PharmD PhD MPHg
aDermatology Consulting Services, PLLC, High Point, NC
bCenter for Dermatology and Laser Surgery, Sacramento, CA
cUniversity of Washington, School of Medicine, Seattle, WA
dIndiana University School of Medicine, Indianapolis, IN
ePhysicians Skin Care, PLLC, Louisville, KY
fIcahn School of Medicine at Mount Sinai, New York, NY
gOrtho Dermatologics,
* Bridgewater, NJ *Ortho Dermatologics is a division of Bausch Health US, LLC
Abstract
Background: Intrinsic properties of vehicles used to deliver topical therapies can profoundly impact drug penetration, efficacy, patient acceptance, and treatment adherence. Therefore, advancements in vehicle technology demand sophisticated, quantitative approaches to describe and differentiate topical formulations. The objective of these studies was to quantitatively evaluate spreadability of two topical formulations for the treatment of acne via in vitro rheological measurement (how a substance’s flow characteristics change under applied stress or force) and spreadability on living skin.
Methods: Rheological characteristics (shear-thinning, rigidity, yield stress, and yield strain) of tazarotene 0.045% lotion and trifarotene 0.045% cream were measured using 5 samples of each product. In a clinical split-body study, each formulation was applied to one side of the back of healthy volunteers, and the extent to which each formulation could be spread was measured.
Results: Compared to trifarotene cream, tazarotene lotion demonstrated lower mean viscosity, rigidity, and yield stress, and higher yield strain, suggesting a superior spreadability profile. This finding was confirmed in the split-body study of 30 healthy White adults, in which the average area of spread was significantly larger for tazarotene lotion than trifarotene cream (167.0 vs 130.3 cm2; P<0.001).
Conclusions: Rheological assessment effectively predicted the superior spreadability of tazarotene 0.045% lotion versus trifarotene 0.005% cream on living skin. Given the importance of aesthetics of topical formulations, techniques to quantify these properties may have broad implications when developing novel vehicle formulations for dermatology.
J Drugs Dermatol. 2022;21(3):250-257. doi:10.36849/JDD.6703
INTRODUCTION
The vehicle used to deliver a topical therapy composes the majority of a drug’s formulation, and vehicle optimization thus represents an opportunity to maximize drug penetration, efficacy, patient acceptance, and treatment adherence.1,2 Vehicles used for topical drug delivery must strike a delicate balance between acting as liquids, which are easy to spread but can run out of their container or off the skin immediately upon application, and as solids, which stay in place but cannot be deformed and do not spread. Thus, topical products are often differentiated based on simplistic, qualitative descriptions of their application characteristics: lotions are lighter and less greasy than creams, for example, whereas creams are thicker and more hydrating than lotions. Such perception-based characterizations are, however, subjective and may inaccurately capture the unique properties of any given formulation. This is especially true of vehicles developed utilizing novel technologies, which have been formulated to behave differently upon application than traditional ones and may thus defy traditional definitions. Such advancements demand a more sophisticated approach to describing and differentiating topical formulations.
Quantitative, objective measurements of a topical formulation’s physical properties can be attained by assessing its rheology—how its flow characteristics change under applied stress or force,3 as when a lotion is rubbed on the skin. Common rheological measurements include shear thinning, rigidity, yield stress, and
