Effect of Sebum and Ointment Rubbing on the Skin Permeation of Triamcinolone Acetonide from White Petrolatum Ointment

Abstract

It is very important to clarify the partition and diffusion of drugs into and through the skin barrier for effective therapy when using topical drug formulations. Several studies have already been carried out on the release and skin permeation of drugs from topical formulations such as ointments and creams. [1][2][3][4] We have studied the effect of sebum or relative skin lipids on the release and skin permeation of drugs from topical formulations. When a pressure sensitive adhesive (PSA) patch containing lidocaine was applied to hairless rat skin, the drug crystal was dissolved in the PSA by the sebum or skin lipids that penetrated from the skin surface to the PSA matrix.5) In addition, release and skin permeation of a hydrophilic drug were increased from white petrolatum by addition of sebum or skin lipids. 6) Cholesterol, cholesteryl oleate and ceramide were detected in a white petrolatum which was pre-applied to hairless rat skin. 6) However, the effect of sebum or skin lipids has not yet been determined on the skin permeation of lipophilic drugs.Semisolid formulations such as ointments and creams are applied to skin, sometimes by rubbing on the skin surface. This is a key difference of semisolid formulations compared to skin adhesive topical formulations like patches and plasters. Rubbing ointments on skin may increase the skin permeation of entrapped drugs in ointments. However, quantitative studies have not yet been done on the ointment-rubbing effect on the skin permeation of drugs.In the present study, a broadly used steroidal drug, triamcinolone acetonide (TA) (MW; 434.5, mp; 290°C, log P; 2.53, solubility in water at 25°C; 22.05Ϯ0.05 mg/ml, and solubility parameter; 9.45 (cal/cm 3 ) 1/2 ) was selected as a model lipophilic drug, and white petrolatum was used as an ointment base.7) The effect of sebum or skin lipids was determined on the dissolution and skin permeation of TA in and from white petrolatum, respectively. The rubbing effect of the ointment on the skin surface was also measured on the skin permeation and skin concentration of TA. MATERIALS AND METHODSMaterials and Experimental Animals TA powder (mean diameter; 5 mm) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). White petrolatum was purchased from Kosakai Pharmaceutical, Ltd. (Tokyo, Japan). Other chemicals and solvents were of reagent grade or HPLC grade and used without further purification. Male hairless rats (WBM/ILA-Ht, 8-9 weeks-old, body weight: 230-260 g) were obtained from the Life Science Research Center, Josai University (Sakado, Saitama, Japan) or Ishikawa Experimental Animals (Fukaya, Saitama, Japan). The animal feeding and experiments were conducted according to the ethical committee in Josai University.Preparation of White Petrolatum Ointment Containing Triamcinolone Acetonide White petrolatum ointments (original ointment) of TA at concentrations of 10-50 mg TA/g (1.0-5.0%) were prepared by thoroughly mixing with white petrolatum to prepare a "TA original ointment." In order to evaluate the effect of s...

Evaluation of the Skin Blanching of Topically Applied Steroids Using a Chroma Meter in Animals

“…Then, 1.0% CP or PS cream (Ca. 300 mg) was placed in a disc-shaped cell cap [6], and the cell cap was applied to the epidermal side of the hydrated dorsal skin, which was placed in a diffusion cell with an effective permeation area of 0.95 cm 2 , surrounded by a water jacket connected to a water bath at 32°C, while 3.0 ml of pH 7.4 PBS or 0.54 µmol/ ml DFP/pH 7.4 PBS was applied to the dermal side [18]. The receiver compartment was agitated using a magnetic stirrer and a stirrer bar.…”

“…before application of the cream to this site, the skin color was measured using a Chroma Meter (CR-400, Konica Minolta Sensing, Inc., Tokyo, Japan). Then, 0.005, 0.01, 0.1, or 1.0% CP or PS cream (Ca 100 mg) was rubbed into the application site at a pressure of 1.87-3.12 N/cm 2 using a rubber-covered forefinger for 30 s [6]. Similarly, drug-free hydrophilic cream was also applied to some sites using the same method as the control.…”

Imaging Analysis Enables Differentiation of the Distribution of Pharmaceutical Ingredients in Tacrolimus Ointments

“…Since the API concentration in solvent is known to influence its skin permeation, 27,28 the solvent concentration in the ointments is an important factor. The solvent concentrations in TCR ointments that were detected using GC-MS are shown in Table IV.…”

Rubbing the skin when removing makeup cosmetics is a major factor that worsens skin conditions in atopic dermatitis patients

“…Okuda and Yoshiike reported that rubbing the skin may worsen skin functions 9 . Furthermore, skin friction, massaging, and rubbing are related to stratum corneum functions 13‐16 and often increase the chemical penetration rate of the skin 17,18 …”

“…9 Furthermore, skin friction, massaging, and rubbing are related to stratum corneum functions [13][14][15][16] and often increase the chemical penetration rate of the skin. 17,18 Many people recognize that rubbing their skin may worsen their skin conditions. In this evaluation, all subjects considered that they did not rub their skin hard during the cleansing and felt that their own cleanser did not worsen their skin symptoms (data not shown).…”