Distribution of salicylic acid in human stratum corneum following topical application in vivo: a comparison of six different formulations

doi:10.1016/S0378-5173(99)00217-3

International Journal of Pharmaceutics

Volume 188, Issue 2, 25 October 1999, Pages 145-153

https://doi.org/10.1016/S0378-5173(99)00217-3 Get rights and content

Abstract

Distribution of salicylic acid in human stratum corneum from treatment of six different formulations was assessed by quantitation of drug content in sequentially tape-stripped stratum corneum after a single 2-h dose was applied unoccluded to skin on the ventral forearm of four female subjects. The profile and total amounts of stratum corneum removed in 20 tape-strips varied among different types of formulations. With or without normalization by the total stratum corneum weights removed, the extent of drug delivery to the stratum corneum decreased in the following order: SA (5%)>>SAC (10%), Duofilm (16.7%)>TSSS (2%)>SAO (10%), Salic (2.5%), the percentage in parentheses indicating the salicylic acid concentration in each formulation. The greatest topical bioavailability was observed for the alcoholic solution containing glycerol (SA). The 10% collodion formulation (SAC) was found to deliver an amount of salicylic acid into the stratum corneum 2-fold greater than 10% ointment formulation (SAO). Use of absorption ointment (TSSS) also increased the uptake of salicylic acid into the stratum corneum in comparison with formulations based on simple ointment (SAO) and oil in water (o/w) cream (Salic). The partitioning of salicylic acid from collodion formulations (SAC and Duofilm) appeared to be concentration-independent. The results of this study indicate that topical bioavailability of salicylic acid in the stratum corneum varies substantially among different formulations.

Introduction

Salicylic acid is a well-established keratolytic and has been used in concentrations of 0.5–60% in almost any base, including ointment, liquid, cream or plaster, for the treatment of acne, psoriasis, warts, ichthyosis and other hyperkeratotic disorders (Chren and Bickers, 1990, Tong and Vickers, 1993, AHFS Drug Information, 1996). Historically, the bioavailability of salicylic acid topical formulations has been evaluated based on its keratolytic effect and clinical efficacy (Baden and Alper, 1973, Davies and Marks, 1976, Nook, 1987). Various methods have been proposed to measure the effect of salicylic acid on the rate of cell loss from the epidermal surface, including analysis of released proteins (Christensen et al., 1978), disappearance of dansyl chloride fluorescent staining (Roberts et al., 1980), silver nitrate staining (Roberts et al., 1980, Nook, 1987), histological examination of skin biopsies (Davies and Marks, 1976, Roberts et al., 1980) and forced desquamation techniques (Roberts et al., 1980). Although these techniques may be useful to demonstrate the keratolytic effect of salicylic acid in the stratum corneum, they do not reveal any information regarding the efficiency of salicylic acid delivery from different formulations and its local concentration in the target site. Because of the tedious nature and frequent impracticality of such studies, very limited effort has been made to evaluate the mechanism and extent of salicylic acid absorption into human skin and the relationship between local salicylic acid concentration and its pharmacological activity. Lodén et al. (1995) utilized a tape-stripping method to evaluate the effect of skin absorption of salicylic acid on the binding forces within the stratum corneum. However, no relationship between these two parameters has been established. Studies with corticosteroids have indicated that the drug concentration in the stratum corneum can be correlated to the pharmacodynamic response, as determined by vasoconstrictor assay, and that the drug concentration may be used to estimate bioavailability of topical formulations (Pershing et al., 1992, Pershing et al., 1994a). Similarly, differential uptake of topical miconazole and ketoconazole into the stratum corneum was correlated with their antifungal activities (Pershing et al., 1994b). Based on these findings, if we consider the stratum corneum as the target site for desquamating activity, salicylic acid concentration in the stratum corneum should provide information regarding its clinical efficacy.

The vehicle of topical formulations influences the drug uptake into the stratum corneum. This study was performed to evaluate the distribution of salicylic acid into healthy human stratum corneum in vivo using a tape-stripping technique. Six different topical formulations of salicylic acid were tested including cream, ointment and solution. The salicylic acid concentrations in those formulations ranged from 2% to 16.7%. The results may provide information about relative bioavailability of various salicylic acid formulations.

Section snippets

Materials

Salicylic acid was purchased from Wako Pure Chemicals (Osaka, Japan). HPLC grade methanol and acetonitrile were purchased from Fisons Scientific Equipment (Loughborough, UK). Six different salicylic acid preparations (SA, Salic, TSSS, Duofilm, SAO and SAC) which were formulated with a variety of bases and salicylic acid concentrations were obtained from the National Cheng Kung University Hospital Pharmacy. Their formulations are listed in Table 1. Other chemicals were of reagent grade and

The amount of stratum corneum removed by tape-stripping

Cumulative amounts of stratum corneum removed with the tape-stripping technique following 2 h application of the six salicylic acid formulations are presented in Fig. 2. The profile of stratum corneum removed was linear and almost identical with treatment of the three semisolid type formulations, TSSS, SAO and Salic, indicating that similar amounts of stratum corneum were removed with each tape-strip from these three formulations. For the three solution type formulations (SA, SAC and Duofilm)

Acknowledgements

This work was supported in part by Medical Research Fund No. 079 (1997) from National Cheng Kung University Hospital, and Grant NSC 87-2314-B006-032 from the National Science Council of Taiwan.

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Distribution of salicylic acid in human stratum corneum following topical application in vivo: a comparison of six different formulations

Abstract

Introduction

Section snippets

Materials

The amount of stratum corneum removed by tape-stripping

Acknowledgements

J. Invest. Dermatol.

J. Invest. Dermatol.

Surface-acting drugs

Studies on the effect of salicylic acid on normal skin

Br. J. Dermatol.

Distribution and keratolytic effect of salicylic acid and urea in human skin

Skin Pharmacol.

Effect of ointment bases on topical and transdermal delivery of salicylic acid in rats: evaluation by skin microdialysis

J. Pharm. Pharmacol.