Quantification of corticosteroid-induced skin vasoconstriction: visual ranking, chromameter measurement or digital image analysis

Topical corticosteroid formulations have been evaluated by visual grading protocols for many years. Toward a more objective methodology, several instrumental methods have been evaluated for applicability in quantifying the vasoconstriction side-effect that follows corticosteroid application to the skin. Although the chromameter has been adopted by regulatory bodies throughout the world as the current standard for topical bioequivalence determinations, there is considerable criticism of this instrument from several quarters. A preliminary comparison reported here indicates that digital image analysis provides statistically significant results that are similar to those obtained by visual assessment techniques, and shows considerably greater precision than that obtained by the chromameter. Continued evaluation of objective assessment techniques, such as digital imaging, and continued modernisation of regulatory bioequivalence requirements will assist in protecting patients and optimising clinical results

Bioequivalence testing of topical dermatological formulations, the gap between science and legislation

Bioavailability concerns for topical dermatological products are complex and it is especially difficult to determine the bioequivalence of similar topical formulations. Since only small amounts of drug dispersed in an appropriate vehicle are applied to the skin, the amount of drug that actually reaches the systemic circulation is often too small to be easily quantified. Additionally, it can be argued that the relevance of any serum/plasma concentration-time curve of a topical agent is questionable, since the curve reflects the amount of drug after the active moiety has left the site of action. For some topical drugs e.g., topical corticosteroids, it is possible to perform a pharmacodynamic bioassay to obtain acceptable bioequivalence data. In this case, the intensity of the side effect of blanching (vasoconstriction) in the skin caused by topical corticosteroids can be measured. The response is directly proportional to the clinical efficacy, and the skin blanching assay has proved to be a reliable procedure for the determination of topical corticosteroid bioavailability. Recently, we had sight of the results of a topical bioequivalence study, which was conducted for the registration of a new generic corticosteroid cream formulation. In this trial the new formulation was compared to two equivalent product from the local market and bioequivalence was demonstrated by the investigators for all three products. These results were examined with interest as the respective reference products have been used repeatedly as standard formulations in our laboratory. However, one of these reference formulations has consistently shown superior bioavailability in our trials, but was not demonstrated to be superior in the study results examined. In the present publication an overview of topical bioequivalence testing in general is given and the difficulties occurring in practice, for topical corticosteroid formulations in particular, are demonstrated

Analysis of chromameter results obtained from corticosteroid-induced skin blanching assay: comparison of visual and chromameter data

In a Guidance document, the American FDA recommends the use of a Minolta chromameter rather than the human eye for the quantitative assessment of the pharmacodynamic blanching response produced by topical application of corticosteroids. The purpose of this study was to compare the appropriateness of the human eye and two models of chromameter for the estimation of skin blanching, in terms of the quality of the data generated by each method. The corticosteroid-induced skin blanching from four different betamethasone 17-valerate cream formulations was compared in a typical human skin blanching trial. The optimized assay methodology routinely practised in our laboratories was utilized. The blanching responses were assessed visually by three trained, independent observers and recorded by two chromameters (Minolta model CR-200 and model CR-300). The topical availability of the four creams was determined using visual scoring and chromameter measurements. All data were manipulated in such a manner as to produce a blanching response versus time profile from which AUBC analysis could be performed. Good correlation was observed between the visual assessments made by three independent observers. In contrast, moderate correlation was determined between visual, CR-200 and CR-300 measurements. Surprisingly, no direct linear relationship between the AUBCs produced by the two chromameters was observed indicating that the quality of the data obtained from the two instruments may not be equal. This investigation also indicated that the use of the chromameter is not completely objective. Visual scoring and chromameter measurement produce data sets that differ in quality. Each procedure needs to be validated and investigators have to be trained for both visual assessment and the operation of the chromameter, particularly with regard to the manipulation of the measuring head of the instrument

Chromametry: measuring precision of diurnal and local variation of human forearm skin colour

Chromameters are compact portable instruments used for the assessment of surface colour based on the tristimulus analysis of a reflected xenon light pulse, and have been used for the quantification of erythema in the study of irritant dermatitis, and corticosteroid-induced skin blanching in the vasoconstriction assay. The variability and the reproducibility of chromameter results were investigated since it is known that the location and application force of the measuring head on the skin and the orthostatic maneuver of the arms influence the colour measurement. Furthermore the diurnal variation and the homogeneity of forearm skin colour were investigated

Individualising drug dispensaries in a university hospital

BACKGROUND: In hospitals and other healthcare institutions drugs are routinely stored in designated satellite areas on the wards. Often ad hoc decisions are made by clinicians and nurses regarding drug type and quantity to be stored. As a result the number of different drugs and drug packages in storage tends to increase, which may lead to inefficient drug handling and become a potential risk factor in the medication control process. Based on an extended analysis of drug inventories on three different wards it was hypothesized that a ward-individualised formulary (WIF) can halve the number of different drugs and drug packages in a drug dispensary and hence reduce bound capital, money lost through expired drugs, and facilitate safer drug handling. The interdisciplinary intervention described here took place on three 40-bed wards in a 700-bed university hospital housing patients in general internal medicine, haematology, nephrology and oncology. METHODS: A WIF was defined by including all drugs from the hospital formulary ordered at least three times in the past six months. A pharmacist, a nurse and a clinician reviewed the inclusion list of drugs and clinicians were strongly encouraged to prescribe drugs primarily from the WIF. Drugs excluded from the WIF were removed from the drug dispensaries and the number of included drug packages stored in the remote dispensaries was reduced according to their order history. Drug inventory on the wards was monitored from February 2004 to April 2006. RESULTS: The initial drug dispensary inventories on wards A, B and C consisted of 2031, 1667 and 1536 packages with 943, 897 and 831 different drugs valued at h 83 931, h 44 590 and h 57 285. respectively. After adjusting the drug dispensaries according to the WIF drug dispensary inventories on wards A, B and C consisted of 808 (-60%), 600 (-64%) and 485 (-68%) packages with 415 (-56%), 334 (-63%) and 376 (-55%) different drugs valued euro 28 012 (-67%), euro 10 381 (-77%) an euro 17 898 (-69%). The overall reductions the number of packages, the different drugs and the drug value were comparable (<50%) and remained low during the entire observation time (A: 18 months, B: 13 months, C: 8 months). CONCLUSION: Rearranging dispensaries by individualizing the drug inventory according to the needs of the ward by introducing a WIF is a valuable means to significantly (<50%) reduce [1] the number of drug packages, [2] the number of different drugs stored and [3] the capital bound drugs. The positive effects of the WIF are supported by the interdisciplinary interaction of the different professional groups involved in the medication process. The leaner drug dispensaries offer optimal basic conditions for introducing new IT-based systems to further increase the safety of the medication process

Bioavailability, Antipsoriatic Efficacy and Tolerability of a New Light Cream with Mometasone Furoate 0.1%

Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with re-spect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin. Copyright (C) 2012 S. Karger AG, Base

Comparison of visual CR-200 and CR-300 chromameter data obtained from the corticosteroid-induced skin-blanching assay

In a recent Guidance document the American FDA recommended the use of a chromameterrather thanthe human eye for the assessment of the pharmacodynamic blanching response produced after topical application of corticosteroids. The purpose of this study was to investigate the appropriateness of the human eye and two types of chromameter for the estimation of skin blanching

Utilization of duckweed as fish meal replacement in common carp (Cyprinus carpio)

Duckweed, the family Lemnaceae, comprises a group of around 40 different aquatic flowering plant species. They can grow very fast, producing higher biomasses compared to terrestrial plants (up to 79 t DM ha-1 a-1, Leng et al. 1995). Furthermore, they are very efficient in uptake of nitrogen and phosphorous and are producing protein of high quality (Stadtlander et al. 2019). Protein contents usually range between 25 to 35% of DM (dry matter) but have been reported to be as high as 45% of DM. Duckweed (Spirodela polyrhiza) has been successfully grown on diluted cow slurry and been fed to rainbow trout fry (Stadtlander et al. 2019). Common carp (Cyprinus carpio) is among the most important cultured fish species in the world, with a production of 4.13 mio t in 2017, and cyprinids (carp-like fish) in general contribute around 50% of global aquaculture fish production. In this study, we tested two different duckweed (S. polyrhiza) meals, one dried (DWD) and one fermented (DWF), in three different concentrations in the diet of carp fry and compared results to a duckweed free control (C)