A Method for Measuring the Surface Free Energy of Topical Semi-solid Dosage Forms.

Our aim was to determine the surface free energy (SFE) of semi-solid dosage forms (SSDFs) by establishing a reproducible method for measuring the contact angle of liquids to SSDFs. Four SSDFs were used: petrolatum, an oil/water (O/W) and a water/oil (W/O) cream, and an alcohol-based gel. The SSDFs were evenly spread on a glass slide, and the change in contact angle over time was measured by dropping water, glycerol, diiodomethane and n-hexadecane as the test liquids. Depending on the combination of test liquid and SSDF, the contact angle was either constant or decreased in an exponential manner. Contact angles may have decreased in an exponential manner because the reaction between the test liquid and the SSDF altered the interfacial tension between the two phases and changed the surface tension of the test liquid and the SFE of the SSDF. The contact angle of the test liquid to the SSDF could be determined reproducibly using the initial contact angle immediately after dropping the liquid on the SSDF as the contact angle before reaction. Using the obtained contact angles and the Owens-Wendt-Rabel-Kaelble equation, we calculated the SFE and its component for the SSDFs tested and found that the results reflect the physicochemical properties of SSDFs. Furthermore, the work of adhesion (WA) of the SSDF to Yucatan micropig skin was calculated using the SFE for the SSDFs. Interestingly, the WA values for all SSDFs tested were comparable.

[Prediction of Wettability and Adhesion of Lotion to Skin Based on the OWRK Method].

In this study, we propose a new technique for evaluating wetting and adhesion of lotions to skin using surface tension measurements, contact angle measurements and calculations based on the Owens-Wendt-Rabel-Kaelble (OWRK) method. Three prescription lotions (Napageln® Lotion 3%, Sumilu® Lotion 3% and Felbinac Lotion 3% ï½¢Rakool｣） and two over-the-counter lotions (Feitas® Lotion and Salomethyl® FB Lotion α) were used. Based on the dispersive and polar components of the surface free energy of Yucatan micro pig (YMP) skin, isograms of contact angle (wetting envelope) and adhesion work of the YMP skin surface were constructed. Plotting the surface tension and its polar component of lotions on this isogram revealed that it is possible to predict the wettability and adhesion of lotions to YMP skin. Such diagrams can be easily constructed even using the surface free energy of other types of skin, such as that of humans and hairless mice. This evaluation method may be applicable to other external use medicines.

The Comparison of Surface Free Energy of Human, Yucatan Micropig, and Hairless Mouse Skins and Influence of Surfactant on Surface Free Energy of the Skin.

Surface free energy (SFE) is an important factor for evaluation of wettability or adhesion. Thus, the SFE of a Yucatan micropig (YMP) skin and a hairless mouse (HM) skin, which are commonly used in skin permeation studies instead of human skin, were compared with the human skin. Contact angles of water and 1-bromo naphthalene to skin were measured and the SFE was calculated using the Owens-Wendt equation. The SFE of the human abdominal skin was 40 mN/m and its polar component σsp was as low as 2 mN/m, which was similar to that of the low sebum skin reported previously. In the case of the YMP skin, σsp was high on the surface but similar to that obtained after the skin was tape-stripped twice. The HM skin showed similar SFE as that of the human skin. When the surfactant was applied on the skin, wiped, and dried, the remaining surfactant increased the SFE in σsp; however, the original SFE was obtained after rinsing with water. The YMP skin and HM skin is similar to the human abdominal skin with a low sebum level. Thus, they are also good skin models for studying wettability or adhesion of a substance.

Highly Viscoelastic Reverse Wormlike Micellar Systems from a Mixture of Lecithin, Polyglycerol Fatty Acid Monoesters, and an Oil.

We report new lecithin reverse wormlike micelles with high viscoelasticity formed using lecithin/polyglycerol fatty acid monoester (PGLFA)/oil systems. In this study, the influence of the amphiphilicity (i.e., hydrophile-lipophile balance, HLB) of PGLFA on the phase behavior and rheological properties of reverse wormlike micelles was investigated in detail. PGLFAs with degrees of polymerization of polyglycerol varying between 6-40 and constituent fatty acids with chains between 6-18 carbon atoms long were used. Partial phase diagrams of the lecithin/PGLFA/n-decane systems indicated that the appropriate PGLFA could change the lecithin/oil solution into a highly viscoelastic solution comprising reverse wormlike micelles. Rheological measurements showed that all systems that formed reverse wormlike micelles exhibited an unusual phenomenon called "shear-thickening". Furthermore, reverse wormlike micelles grew as the PGLFA concentration increased and the zero-shear viscosity (η0) of the solution rapidly increased. Our results indicate that the magnitude of the maximum η0 depends on the degree of polymerization of the constituent polyglycerol in the PGLFA, while the size of the reverse micellar region and the highly viscous region in the phase diagram depends on the HLB value of the PGLFA.

Skin Permeation of Testosterone from Viscoelastic Lecithin Reverse Wormlike Micellar Solution.

We evaluated testosterone-containing lecithin reverse wormlike micelles (reverse worms) composed of a polar substance/lecithin/isopropyl myristate for transdermal application. Water, D-ribose, or tetraglycerol were used as the polar substance and were key ingredients for forming the reverse worms. Using the reverse worms, 1 wt% of testosterone could be stably solubilized. When using D-ribose as polar substance, the maximum zero-shear viscosity of the reverse worms solution was higher than that of systems using water or tetraglycerol as the polar substance. The mechanism of skin permeation of testosterone from reverse worms solution was elucidated using skin permeation experiments with hairless mouse skin. When the structure of the reverse worms transitioned to lamellar liquid crystals at the skin/formulation interface, testosterone became supersaturated in the formulations. The structural transition occurred in systems using water or D-ribose as the polar substance, increasing the flux of testosterone. The flux of testosterone from reverse worms solution thus depends on the type of polar substance used.

A new reverse worm-like micellar system from a lecithin, multivalent carboxylic acid and oil mixture.

We developed new lecithin organogels composed of reverse worm-like micelles with lecithin/multivalent carboxylic acid/oil systems, and discussed their phase behavior and rheological properties. The most important findings in this study are the following. From a screening test of many carboxylic acids for gelation, it was found that the number and position of the carboxyl groups of the multivalent carboxylic acids are the determinants for the formation of reverse worm-like micelles, and appropriate carboxylic acids such as citric acid and 1,2,3-propanetricarboxylic acid can change the lecithin/oil solution into a gel. Furthermore, upon addition of these carboxylic acids, the zero-shear viscosity of solutions increased monotonically until phase separation or cloudiness occurred. For example, when citric acid was used, the maximum zero-shear viscosity of the solution was 70,000,000 times larger than that of n-decane. From studies on the scaling of rheological parameters, it was found that further addition of multivalent carboxylic acids not only induced the formation of linear reverse worm-like micelles but also brought about their branching.

New lecithin organogels from lecithin/polyglycerol/oil systems.

New liquid substances that induce the formation of lecithin organogels composed of reverse worm-like micelles were studied. The phase behavior and rheological properties of lecithin/polyglycerol (PGL)/oil systems were investigated in detail; the polymerization degrees of the glycerol residues were 3, 4, 6, 10, 20, and 40. From the partial phase diagrams of the lecithin/PGL/n-decane systems, it was apparent that highly viscoelastic reverse worm-like micelles formed upon the addition of small amounts of the PGL, except in the case of the PGL with a polymerization degree of 40. Steady-flow viscosity measurements showed that the zero-shear viscosity (η0) of the reverse worm-like micelles rapidly increased with the concentration and polymerization degree of the PGLs, reaching a maximum value that was 750,000 times the viscosity of n-decane and thus resulting in the growth of these micelles. It is noteworthy that the η0 values of lecithin organogels formed using PGLs were higher than the η0 value of the lecithin organogel formed using glycerol (GL). From dynamic viscoelasticity measurements, it was shown that the viscoelastic behavior of the reverse worm-like micelles was consistent with the single Maxwell model, which is the basic model of a viscoelastic body. It follows from this study that PGLs are useful liquids because they can induce the formation of lecithin organogels with high viscoelasticity, as do other liquids such as water, glycerol, ethylene glycol, and formamide.