Viscoelastic evaluation of topical creams containing microcrystalline cellulose/sodium carboxymethyl cellulose as stabilizer.
The purpose of this study was to examine the viscoelastic properties of topical creams containing various concentrations of microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel(R) CL-611) as a stabilizer. Avicel CL-611 was used at 4 different levels (1%, 2%, 4%, and 6% dispersion) to prepare topical creams, and hydrocortisone acetate was used as a model drug. The viscoelastic properties such as loss modulus (G"), storage modulus (G'), and loss tangent (tan delta) of these creams were measured using a TA Instruments AR 1000 Rheometer and compared to a commercially available formulation. Continuous flow test to determine the yield stress and thixotropic behavior, and dynamic mechanical tests for determining the linear viscosity time sweep data, were performed. Drug release from the various formulations was studied using an Enhancer TM Cell assembly. Formulations containing 1% and 2% Avicel CL-611 had relative viscosity, yield stress, and thixotropic values that were similar to those of the commercial formulation. The elastic modulus (G') of the 1% and 2% formulation was relatively high and did not cross the loss modulus (G"), indicating that the gels were strong. In the commercial formulation, G' increased after preshearing and broke down after 600 seconds. The strain sweep tests showed that for all formulations containing Avicel CL-611, the G' was above G" with a good distance between them. The gel strength and the predominance of G' can be ranked 6% > 4% > 2%. The strain profiles for the 1% and 2% formulations were similar to those of the commercial formulation. The delta values for the 1% and 2% formulations were similar, and the formulations containing 4% Avicel CL-611 had lower delta values, indicating greater elasticity. Drug release from the commercial preparation was fastest compared to the formulations prepared using Avicel CL-611, a correlation with the viscoelastic properties. It was found that viscoelastic data, especially the strain sweep profiles of products containing Avicel CL-611 1% and 2%, correlated with the commercial formulation. Rheological tests that measure the viscosity, yield stress, thixotropic behavior, other oscillatory parameters such as G' and G" are necessary tools in predicting performance of semisolids. (+info)
Exceptionally high protection of photocarcinogenesis by topical application of (--)-epigallocatechin-3-gallate in hydrophilic cream in SKH-1 hairless mouse model: relationship to inhibition of UVB-induced global DNA hypomethylation.
(--)-Epigallocatechin-3-gallate (EGCG) has been shown to have potent antiphotocarcinogenic activity, but it was required to develop a cream-based formulation for topical application. For topical application, we tested hydrophilic cream as a vehicle for EGCG. Treatment with EGCG ( approximately 1 mg/cm(2) skin area) in hydrophilic cream resulted in exceptionally high protection against photocarcinogenesis when determined in terms of tumor incidence, tumor multiplicity, and tumor size in a SKH-1 hairless mouse model. EGCG also inhibited malignant transformation of ultraviolet B (UVB)-induced papillomas to carcinomas. In order to determine the mechanism of prevention of photocarcinogenesis, we determined the effect of EGCG on global DNA methylation pattern using monoclonal antibodies against 5-methyl cytosine and DNA methyltransferase in the long-term UV-irradiated skin because altered DNA methylation silencing is recognized as a molecular hallmark of human cancer. We found that treatment with EGCG resulted in significant inhibition of UVB-induced global DNA hypomethylation pattern. Long-term application of EGCG did not show any apparent sign of toxicity in mice when determined in terms of skin appearance, lean mass, total bone mineral content, and total bone mineral density but showed reduction in fat mass when analyzed using dual-energy X-ray absorptiometry. These data suggest that hydrophilic cream could be a suitable vehicle for topical application of EGCG, and that EGCG is a promising candidate for future cancer therapies based on its influence on the epigenetic pathway. (+info)
Effect of simultaneous insertion of oleaginous base on the absorption and on the anticonvulsant effect of diazepam suppository.
To clarify the drug-base interaction between diazepam (DZP) suppository and oleaginous base, we investigated the effect of simultaneous combination of oleaginous base on the absorption and on the anticonvulsant effect of DZP Suppository in rats. Simultaneous insertion of DZP suppository and oleaginous base significantly decreased maximum concentration (C(max)) and area under the blood concentration-time curve (AUC) of plasma DZP concentrations. Administration of DZP suppositories (2.5, 5 mg/kg) dose-dependently suppressed the pentylenetetrazol (PTZ)-induced seizures, and the anticonvulsant effect of DZP suppository (5 mg/kg) was reduced by simultaneous insertion of oleaginous base. In an in vitro study using a suppository release apparatus, simultaneous combination of DZP suppository and oleaginous base (1.5-98 mg) significantly decreased the accumulative release of DZP in a dose-dependent manner. These results suggested that when DZP suppository and oleaginous base are inserted simultaneously, the released DZP distributes partially to the oleaginous base, and this phenomenon is related to the decreases in the plasma concentration and the anticonvulsant effect of DZP. (+info)
Keratosis follicularis (Darier-White disease), with an unusual palmoplantar keratoderma.
A 38-year-old woman presented with widespread, hyperkeratotic papules and plaques that had been present since childhood. Her mother, brother, and son have similar lesions. A diagnosis of keratosis follicularis was made, which has been treated with isotretinoin. Palmoplantar lesions of keratosis follicularis have been described as discrete, punctate keratoses, hyperkeratotic papules, small pits, or keratin-filled depressions. This patient has an unusual palmoplantar keratoderma in association with keratosis follicularis. The lesions are elevated, discrete, filiform, hyperkeratotic spires, which coalesce into large, hyperkeratotic plaques on the palms and soles. (+info)
Homologous fibronectin enhances healing of excised wounds in rats.
In order to evaluate the effects of a topical application of homologous fibronectin on the healing of skin wounds, we made 2 excisional wounds on the back skin of each rat, applied ointment with or without fibronectin purified from citrated homologous plasma, and evaluated the effect according to wound size and microscopic findings. Excised lesions treated with carrier alone, but the difference was significant only in the early phase of wound healing, 2 and 3 days, according to wound size and microscopic changes. A significant decrease in wound size could be found in both groups, treated with ointment containing and not containing fibronectin, between day 4 and 9 when wound contraction was a major contributor to wound closure. Therefore it can be concluded that topical application of fibronectin has a beneficial effect on wound healing during its early phase, but no significant influence on wound contraction. (+info)
Tick infestation of the eyelid: a case report in a child.
A three-year-old girl presented with a small brown lesion on the right upper eyelid margin. Close examination revealed an insect body attached to the eyelid margin. Microscopic examination of the specimen identified the species of the organism as Ixodes ricinus. The tick was completely removed with blunt forceps. She was treated with lid toilet, irrigation, and application of topical 0.3% ciprofloxacin four times daily to the affected eye. The lesion healed without scarring after one week. No systemic symptoms were observed. Mechanical removal with blunt forceps may be a quick, easy, safe and effective treatment for ticks located on the eyelids. (+info)
Effect of sebum and ointment rubbing on the skin permeation of triamcinolone acetonide from white petrolatum ointment.
Effect of sebum and ointment rubbing was evaluated on the permeation of a model steroidal drug, triamcinolone acetonide (TA), from white petrolatum ointment through excised hairless rat skin. Two kinds of white petrolatum ointment containing TA at a concentration of 1.0% were made using a "pre-applied ointment," which was made by applying and recovering white petrolatum on and from the rat skin, respectively, and the "original ointment." Solubility and skin permeation of TA in and from both the ointments were measured and compared. TA solubility in the pre-applied ointment was about twice to that of the original ointment. Full-thickness skin and stripped skin permeabilities of TA from pre-applied ointment were about 2.3- and 1.5-times higher than those from the original ointment. In addition, the calculated partition coefficient of TA from pre-applied ointment to full-thickness skin was 2.7-times that of the original ointment. Next, the ointment-rubbing effect was determined. Skin permeation of TA from 1.0% TA original ointment with a 30 s-rubbing was 9-times higher than that after drug-free ointment-rubbing and application of 1.0% TA original ointment. The increase in solubility and skin permeation of TA due to pre-applied ointment is probably due to dissolution of TA by skin lipids extracted from the skin surface. Ointment rubbing increases the transient decrease in skin impedance and enhanced delivery of ointment base to the skin. These results are useful for development of ointment formulations and skin penetration mechanisms from an ointment base. (+info)
Chemopreventive efficacy of topical difluoromethylornithine and/or triamcinolone in the treatment of actinic keratoses analyzed by karyometry.
OBJECTIVE: To determine whether low-dose topical applications of difluoromethylornithine (DFMO) with or without Triamcinolone (Fougena, Melville, New York, U.S.A.) to moderately sun-damaged skin with actinic skin keratoses are efficacious. STUDY DESIGN: There were 4 topically administered, 6-month treatments, DFMO + Eucerin (Beiersdorf Inc., Hamburg, Germany), DFMO + Triamcinolone, Triamcinolone + Eucerin and Eucerin + Eucerin (to serve as double placebo). Participant eligibility included evidence of at least 2 actinic keratoses on each posterolateral forearm as well as moderate to severe evidence of sun-damaged skin, as evaluated by a board certified dermatologist. High resolution digitized imagery of nuclei from histologic sections of 4-mm punch biopsies from sun-damaged skin on the posterolateral forearms was recorded, at baseline and at the end of 6 months of study. RESULTS: With 102 participants and 185 skin biopsies, a total of 16,395 skin cell nuclei were recorded. The nuclei were analyzed to assess the changes in the pattern of the nuclear chromatin. Two specific measures of end point evaluation were computed, including the percentage of nuclei with high values of nuclear abnormality and the reduction of the percentage of nuclei assigned by a discriminant function to the baseline data set. All 3 active interventions, including low-dose topical DFMO, topical Triamcinolone and topical DFMO + Triamcinolone, led to statistically significant reductions of both the number of nuclei with high nuclear abnormality as well as the number of nuclei assigned to the baseline data set. These reductions were found for all 3 treatments involving DFMO or Triamcinolone. For the placebo data sets only small, statistically insignificant increases or decreases of these percentages were observed. CONCLUSION: The low-dose, topical drug interventions were all effective in reducing skin biopsy nuclear abnormality by a statistically significant 15-20%, whereas there was no evidence of a double placebo effect by karyometric assessment. These effects were greater than the case-to-case sampling error. (+info)