A stability-indicating HPLC assay with on-line clean-up for betamethasone 17-valerate in topical dosage forms
- Smith, Eric W, Haigh, John M, Kanfer, Isadore
- Authors: Smith, Eric W , Haigh, John M , Kanfer, Isadore
- Date: 1985
- Language: English
- Type: Article
- Identifier: vital:6421 , http://hdl.handle.net/10962/d1006556
- Description: A stability-indicating high-performance liquid chromatographic method with on-line clean-up has been developed for the analysis of betamethasone 17-valerate in topical dosage forms. A short pre-column containing 10 μm octadecylsilane mounted into the sample loop position of an injection valve was used as the primary clean-up step. The utilization of a diode-array UV detector allowed the quantitative analysis of betamethasone 17-valerate together with its degradation product, betamethasone 21-valerate, as well as the qualitative analysis of these compounds, relevant internal standards and the preservatives chlorocresol and methyl hydroxybenzoate contained in the cream and lotion formulations, respectively. Typically, cream and lotion dosage forms were dissolved in acetonitrile and ointments in tetrahydrofuran, internal standards added and aliquots injected onto the analytical system. Dosage form excipients were retained on the loop column and back-flushed to waste with the aid of a second solvent pump while components of interest were allowed to transfer to the analytical column for quantitative analysis. The method is accurate, precise and stability indicating and permits the rapid on-line analysis of betamethasone 17-valerate from complex topical formulation matrices without prior extractions.
- Full Text:
- Date Issued: 1985
- Authors: Smith, Eric W , Haigh, John M , Kanfer, Isadore
- Date: 1985
- Language: English
- Type: Article
- Identifier: vital:6421 , http://hdl.handle.net/10962/d1006556
- Description: A stability-indicating high-performance liquid chromatographic method with on-line clean-up has been developed for the analysis of betamethasone 17-valerate in topical dosage forms. A short pre-column containing 10 μm octadecylsilane mounted into the sample loop position of an injection valve was used as the primary clean-up step. The utilization of a diode-array UV detector allowed the quantitative analysis of betamethasone 17-valerate together with its degradation product, betamethasone 21-valerate, as well as the qualitative analysis of these compounds, relevant internal standards and the preservatives chlorocresol and methyl hydroxybenzoate contained in the cream and lotion formulations, respectively. Typically, cream and lotion dosage forms were dissolved in acetonitrile and ointments in tetrahydrofuran, internal standards added and aliquots injected onto the analytical system. Dosage form excipients were retained on the loop column and back-flushed to waste with the aid of a second solvent pump while components of interest were allowed to transfer to the analytical column for quantitative analysis. The method is accurate, precise and stability indicating and permits the rapid on-line analysis of betamethasone 17-valerate from complex topical formulation matrices without prior extractions.
- Full Text:
- Date Issued: 1985
A stability-indicating liquid chromatographic method for the analysis of erythromycin in stored biological fluids using amperometric detection
- Stubbs, Christopher, Haigh, John M, Kanfer, Isadore
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6430 , http://hdl.handle.net/10962/d1006592
- Description: A simple, sensitive and reliable high-performance liquid chromatographic procedure has been developed for the determination of erythromycin in human serum and urine using amperometric detection. A solid-phase extraction procedure was used followed by chromatography on a reverse-phase column. The mean recovery of erythromycin from serum and urine was 80%. This method allows both erythromycin and its principle degradation product, anhydroeythromycin, to be determined during a period of sample storage at 4 degree C and minus 15 degree C. The method is sufficiently sensitive and precise and is thus highly suited for use in both pharmacokinetic and stability studies.
- Full Text:
- Date Issued: 1987
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6430 , http://hdl.handle.net/10962/d1006592
- Description: A simple, sensitive and reliable high-performance liquid chromatographic procedure has been developed for the determination of erythromycin in human serum and urine using amperometric detection. A solid-phase extraction procedure was used followed by chromatography on a reverse-phase column. The mean recovery of erythromycin from serum and urine was 80%. This method allows both erythromycin and its principle degradation product, anhydroeythromycin, to be determined during a period of sample storage at 4 degree C and minus 15 degree C. The method is sufficiently sensitive and precise and is thus highly suited for use in both pharmacokinetic and stability studies.
- Full Text:
- Date Issued: 1987
Accuracy and reproducibility of the multiple-reading skin blanching assay
- Smith, Eric W, Meyer, Eric, Haigh, John M
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M
- Date: 1992
- Language: English
- Type: Book chapter
- Identifier: vital:6439 , http://hdl.handle.net/10962/d1006625
- Full Text:
- Date Issued: 1992
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M
- Date: 1992
- Language: English
- Type: Book chapter
- Identifier: vital:6439 , http://hdl.handle.net/10962/d1006625
- Full Text:
- Date Issued: 1992
Analysis of chromameter results obtained from corticosteroid-induced skin blanching assay: comparison of visual and chromameter data
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6426 , http://hdl.handle.net/10962/d1006562
- Description: 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.
- Full Text:
- Date Issued: 1999
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6426 , http://hdl.handle.net/10962/d1006562
- Description: 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.
- Full Text:
- Date Issued: 1999
Analysis of chromameter results obtained from corticosteroid-induced skin blanching. I. Manipulation of data
- Smith, Eric W, Haigh, John M, Walker, Roderick B
- Authors: Smith, Eric W , Haigh, John M , Walker, Roderick B
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6424 , http://hdl.handle.net/10962/d1006559
- Description: Purpose. One of the unresolved issues in the FDA Guidance document for topical corticosteroid bioequivalence testing is the method of manipulation suggested for the chromameter data. The purpose of this study was to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriateness of these procedures for comparison with the subjective visually-assessed results. Methods. The human skin blanching assay methodology routinely practiced in our laboratories was utilised and the vasoconstriction produced by two corticosteroid formulations of different potency was assessed visually and instrumentally by use of a Minolta chromameter. The instrumental data were corrected for zero-time and unmedicated site readings. In addition, Euclidean distances were calculated using all data generated by the instrument. Results. Individually the a-, b- and L-scale chromameter values are imprecise and there is negligible vasoconstriction response recorded for the moderately potent formulation. Arithmetical manipulation of the data as suggested by the FDA does not appear to improve the quality of the data in any way. Euclidean distance analysis more closely resembles the visual data and appears to have better precision. Conclusions. It is clear that mathematical correction of chromameter data is unnecessary, especially since the instrumental data are extremely imprecise. Furthermore, the assessment of each individual chromameter index does not adequately characterise the blanching response profile. It is therefore suggested that Euclidean distance may be a better measure on which to base an analysis of bioequivalence than the truncated data set methodology currently suggested by the FDA.
- Full Text: false
- Date Issued: 1998
- Authors: Smith, Eric W , Haigh, John M , Walker, Roderick B
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6424 , http://hdl.handle.net/10962/d1006559
- Description: Purpose. One of the unresolved issues in the FDA Guidance document for topical corticosteroid bioequivalence testing is the method of manipulation suggested for the chromameter data. The purpose of this study was to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriateness of these procedures for comparison with the subjective visually-assessed results. Methods. The human skin blanching assay methodology routinely practiced in our laboratories was utilised and the vasoconstriction produced by two corticosteroid formulations of different potency was assessed visually and instrumentally by use of a Minolta chromameter. The instrumental data were corrected for zero-time and unmedicated site readings. In addition, Euclidean distances were calculated using all data generated by the instrument. Results. Individually the a-, b- and L-scale chromameter values are imprecise and there is negligible vasoconstriction response recorded for the moderately potent formulation. Arithmetical manipulation of the data as suggested by the FDA does not appear to improve the quality of the data in any way. Euclidean distance analysis more closely resembles the visual data and appears to have better precision. Conclusions. It is clear that mathematical correction of chromameter data is unnecessary, especially since the instrumental data are extremely imprecise. Furthermore, the assessment of each individual chromameter index does not adequately characterise the blanching response profile. It is therefore suggested that Euclidean distance may be a better measure on which to base an analysis of bioequivalence than the truncated data set methodology currently suggested by the FDA.
- Full Text: false
- Date Issued: 1998
Application of the Minolta chromameter to the assessment of corticosteroid-induced skin blanching
- Walker, Roderick B, Haigh, John M, Smith, Eric W
- Authors: Walker, Roderick B , Haigh, John M , Smith, Eric W
- Date: 2000
- Language: English
- Type: Book chapter , text
- Identifier: vital:6451 , http://hdl.handle.net/10962/d1006639
- Full Text:
- Date Issued: 2000
- Authors: Walker, Roderick B , Haigh, John M , Smith, Eric W
- Date: 2000
- Language: English
- Type: Book chapter , text
- Identifier: vital:6451 , http://hdl.handle.net/10962/d1006639
- Full Text:
- Date Issued: 2000
Assessing penetration enhances for topical corticosteroids
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1995
- Language: English
- Type: Book chapter
- Identifier: vital:6442 , http://hdl.handle.net/10962/d1006629
- Description: From introduction: Topical corticosteroids have been used for a wide range of dermatological conditions for the last 4 decades. For many years the topical delivery system was a relatively simple cream or ointment base, with little thought given to improving the formulation as far as drug delivery was concerned. The main emphasis in the initial stages of development was on the alteration of the corticosteroid molecule, in an attempt to produce moieties with a higher intrinsic topical effect with lower mineralocorticoid side effects. Once this avenue of research was exhausted, attention was placed on the lipophilicity of the molecule with the production of various types of esters in an attempt to produce molecules which would pass through the stratum corneum (SC) with reasonable ease. In recent years the nature of the semisolid drug delivery base has received considerable attention.2-5The nature of the vehicle has a profound effect on the rate of release of the topical corticosteroid from the formulation and its passage through the SC. One of the most important aspects of the formulation of the base is the inclusion of substances which aid this trads-SC diffusion, the so-called penetration enhancers.6The modes of action of the various different types of penetration enhancers are reviewed elsewhere in this book. The best method for the assessment of the release of corticosteroids from topical formulations is obviously the clinical tri~. Clinical trials, however, are laborious, costly, and difficult to mount. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid formulations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between formulations. Alternatively, a number of in vitro models exist for this type of assessment, but it is often problematic to obtain correlation with the in vivo situation.
- Full Text:
- Date Issued: 1995
- Authors: Smith, Eric W , Haigh, John M
- Date: 1995
- Language: English
- Type: Book chapter
- Identifier: vital:6442 , http://hdl.handle.net/10962/d1006629
- Description: From introduction: Topical corticosteroids have been used for a wide range of dermatological conditions for the last 4 decades. For many years the topical delivery system was a relatively simple cream or ointment base, with little thought given to improving the formulation as far as drug delivery was concerned. The main emphasis in the initial stages of development was on the alteration of the corticosteroid molecule, in an attempt to produce moieties with a higher intrinsic topical effect with lower mineralocorticoid side effects. Once this avenue of research was exhausted, attention was placed on the lipophilicity of the molecule with the production of various types of esters in an attempt to produce molecules which would pass through the stratum corneum (SC) with reasonable ease. In recent years the nature of the semisolid drug delivery base has received considerable attention.2-5The nature of the vehicle has a profound effect on the rate of release of the topical corticosteroid from the formulation and its passage through the SC. One of the most important aspects of the formulation of the base is the inclusion of substances which aid this trads-SC diffusion, the so-called penetration enhancers.6The modes of action of the various different types of penetration enhancers are reviewed elsewhere in this book. The best method for the assessment of the release of corticosteroids from topical formulations is obviously the clinical tri~. Clinical trials, however, are laborious, costly, and difficult to mount. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid formulations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between formulations. Alternatively, a number of in vitro models exist for this type of assessment, but it is often problematic to obtain correlation with the in vivo situation.
- Full Text:
- Date Issued: 1995
Assessment of some variables affecting the blanching activity of betamethasone 17-valerate cream
- Magnus, Ashley D, Haigh, John M, Kanfer, Isadore
- Authors: Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1980
- Language: English
- Type: text , Article
- Identifier: vital:6396 , http://hdl.handle.net/10962/d1006320
- Description: The effect of concentration and occlusion time on the ability of Betnovate ® cream (betamethasone 17-valerate 0.1%) to produce skin blanching was assessed. Generally, increased concentration or occlusion time produce and increase in the degree of blanching observed, however, a plateau stage is eventually reached where no further increase of blanching occurs.
- Full Text:
- Date Issued: 1980
- Authors: Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1980
- Language: English
- Type: text , Article
- Identifier: vital:6396 , http://hdl.handle.net/10962/d1006320
- Description: The effect of concentration and occlusion time on the ability of Betnovate ® cream (betamethasone 17-valerate 0.1%) to produce skin blanching was assessed. Generally, increased concentration or occlusion time produce and increase in the degree of blanching observed, however, a plateau stage is eventually reached where no further increase of blanching occurs.
- Full Text:
- Date Issued: 1980
Assessment of topical corticosteroid preparations: the human skin-blanching assay
- Haigh, John M, Kanfer, Isadore
- Authors: Haigh, John M , Kanfer, Isadore
- Date: 1984
- Language: English
- Type: text , Article
- Identifier: vital:6374 , http://hdl.handle.net/10962/d1006284
- Description: (From the introduction) Since the introduction of topical corticosteroid formulations, their use has become widespread, being prescribed for a large variety of dermatological conditions. This widespread use has created a need for a reliable method of assessing the various dosage forms of these compounds. Clinical trials are laborious, costly and difficult to mount as well as being impractical for the screening of large numbers of drugs. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid preparations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between patients (Baker and Sattar, 1968). For these reasons a number of methods have been developed for the screening of novel corticosteroids and testing of topical corticosteroid formulations.
- Full Text:
- Date Issued: 1984
- Authors: Haigh, John M , Kanfer, Isadore
- Date: 1984
- Language: English
- Type: text , Article
- Identifier: vital:6374 , http://hdl.handle.net/10962/d1006284
- Description: (From the introduction) Since the introduction of topical corticosteroid formulations, their use has become widespread, being prescribed for a large variety of dermatological conditions. This widespread use has created a need for a reliable method of assessing the various dosage forms of these compounds. Clinical trials are laborious, costly and difficult to mount as well as being impractical for the screening of large numbers of drugs. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid preparations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between patients (Baker and Sattar, 1968). For these reasons a number of methods have been developed for the screening of novel corticosteroids and testing of topical corticosteroid formulations.
- Full Text:
- Date Issued: 1984
Bioavailability and activity of 0.1% amcinonide preparations: comparison with proprietary topical corticosteroid formulations of differing potencies
- Authors: Woodford, R , Haigh, John M
- Date: 1979
- Language: English
- Type: text , Article
- Identifier: vital:6447 , http://hdl.handle.net/10962/d1006634
- Description: The activity of a 0.1% amcinonide cream was compared with those of selected proprietary topical corticosteroid formulations of potencies differing according to the United Kingdom (U.K.) MIMS classification (very potent, potent and moderately potent) using a standard six hour vasoconstrictor assay with multiple reading times. Statistical analysis indicated that 0.1% amcinonide cream feU within the category of a very potent preparation. Three 0.1% amcinonide formulations (cream, combination cream and combination ointment, the last two containing anti-infective agents) were equipotent in the skin-blanching test.
- Full Text:
- Date Issued: 1979
- Authors: Woodford, R , Haigh, John M
- Date: 1979
- Language: English
- Type: text , Article
- Identifier: vital:6447 , http://hdl.handle.net/10962/d1006634
- Description: The activity of a 0.1% amcinonide cream was compared with those of selected proprietary topical corticosteroid formulations of potencies differing according to the United Kingdom (U.K.) MIMS classification (very potent, potent and moderately potent) using a standard six hour vasoconstrictor assay with multiple reading times. Statistical analysis indicated that 0.1% amcinonide cream feU within the category of a very potent preparation. Three 0.1% amcinonide formulations (cream, combination cream and combination ointment, the last two containing anti-infective agents) were equipotent in the skin-blanching test.
- Full Text:
- Date Issued: 1979
Bioequivalence testing of topical dermatological formulations, the gap between science and legislation
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6341 , http://hdl.handle.net/10962/d1006608
- Description: 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.
- Full Text:
- Date Issued: 1998
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6341 , http://hdl.handle.net/10962/d1006608
- Description: 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.
- Full Text:
- Date Issued: 1998
Blanching activities of betamethasone 17-valerate formulations: effect of the dosage form on topical drug availability
- Smith, Eric W, Meyer, Eric, Haigh, John M
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M
- Date: 1990
- Language: English
- Type: Article
- Identifier: vital:6432 , http://hdl.handle.net/10962/d1006602
- Description: The blanching activities of Betnovate© cream, lotion, ointment and scalp application (each containing 0.1 % betamethasone (as the 17-valerate)) were determined using healthy human subjects over a 32 h period in both the occludedand unoccluded modes. Considering that allfour formulation types contained the same label concentration of corticosteroid,it may bepresumed that theformulations would show similar topical drug availability: this was, however, not found to be the case. The scalp application demonstrated the highest topical availability in both the occluded and unoccluded modes. The lotion formulation showed the greatest increase in topical availability on occlusion and the ointment formulation was the least sensitive to the effects of occlusion. These differences, due solely to the effects of the vehicle, may have important clinical implications.
- Full Text:
- Date Issued: 1990
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M
- Date: 1990
- Language: English
- Type: Article
- Identifier: vital:6432 , http://hdl.handle.net/10962/d1006602
- Description: The blanching activities of Betnovate© cream, lotion, ointment and scalp application (each containing 0.1 % betamethasone (as the 17-valerate)) were determined using healthy human subjects over a 32 h period in both the occludedand unoccluded modes. Considering that allfour formulation types contained the same label concentration of corticosteroid,it may bepresumed that theformulations would show similar topical drug availability: this was, however, not found to be the case. The scalp application demonstrated the highest topical availability in both the occluded and unoccluded modes. The lotion formulation showed the greatest increase in topical availability on occlusion and the ointment formulation was the least sensitive to the effects of occlusion. These differences, due solely to the effects of the vehicle, may have important clinical implications.
- Full Text:
- Date Issued: 1990
Can shed snakeskin be considered to be a model membrane for human stratum corneum?
- Haigh, John M, Beyssac, E, Aiache, J M
- Authors: Haigh, John M , Beyssac, E , Aiache, J M
- Date: 1998
- Language: English
- Type: Article
- Identifier: vital:6383 , http://hdl.handle.net/10962/d1006303
- Description: Recently there has been some interest in the use of shed snake skin as a "model" membrane for in vitro diffusion studies. Many different species of snake have been utilised as well as different skin sites (dorsal and ventral). The species is usually named and sometimes the skin site is indicated butsometimes neither species nor skin site is reported. Insome countries it is particularly difficult to obtain human skin for in vitro experimentation and it is therefore important to have alternate biological or synthetic membranes which mimic human skin membranes for diffusion experiments. In South Africa. shed snake skin is easily obtainable from the many snake parks present in the country. Since snakes moult periodically, a single animal can provide repeated sheds, thus reducing interindividual variability. Skins can be obtained without injury to the animal and do not have to be subjected to chemical or heat stress prior to use. The epidermis is shed as a large intact sheet, thus a single snake skin can provide multiple samples. Shed snake skin is not a living tissue, can be stored for long periods at room temperature and is easily transported. Stored and fresh snake skins appear to show no differences in permeability. Since snake skin lacks hair follicles,the problems associated with the transfollicular route of penetration, which may be significant in mammalian skins, can be avoided.
- Full Text:
- Date Issued: 1998
- Authors: Haigh, John M , Beyssac, E , Aiache, J M
- Date: 1998
- Language: English
- Type: Article
- Identifier: vital:6383 , http://hdl.handle.net/10962/d1006303
- Description: Recently there has been some interest in the use of shed snake skin as a "model" membrane for in vitro diffusion studies. Many different species of snake have been utilised as well as different skin sites (dorsal and ventral). The species is usually named and sometimes the skin site is indicated butsometimes neither species nor skin site is reported. Insome countries it is particularly difficult to obtain human skin for in vitro experimentation and it is therefore important to have alternate biological or synthetic membranes which mimic human skin membranes for diffusion experiments. In South Africa. shed snake skin is easily obtainable from the many snake parks present in the country. Since snakes moult periodically, a single animal can provide repeated sheds, thus reducing interindividual variability. Skins can be obtained without injury to the animal and do not have to be subjected to chemical or heat stress prior to use. The epidermis is shed as a large intact sheet, thus a single snake skin can provide multiple samples. Shed snake skin is not a living tissue, can be stored for long periods at room temperature and is easily transported. Stored and fresh snake skins appear to show no differences in permeability. Since snake skin lacks hair follicles,the problems associated with the transfollicular route of penetration, which may be significant in mammalian skins, can be avoided.
- Full Text:
- Date Issued: 1998
Chromametry: measuring precision of diurnal and local variation of human forearm skin colour
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6343 , http://hdl.handle.net/10962/d1006610
- Description: 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.
- Full Text:
- Date Issued: 1998
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6343 , http://hdl.handle.net/10962/d1006610
- Description: 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.
- Full Text:
- Date Issued: 1998
Comparative bioavailability of some locally manufactured betamethasone valerate containing preparations
- Meyer, Eric, Haigh, John M, Kanfer, Isadore
- Authors: Meyer, Eric , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6399 , http://hdl.handle.net/10962/d1006326
- Description: The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application.
- Full Text:
- Date Issued: 1983
- Authors: Meyer, Eric , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6399 , http://hdl.handle.net/10962/d1006326
- Description: The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application.
- Full Text:
- Date Issued: 1983
Comparative blanching activities of proprietary diflucortolone valerate topical preparations
- Coleman, Gerald L, Kanfer, Isadore, Haigh, John M
- Authors: Coleman, Gerald L , Kanfer, Isadore , Haigh, John M
- Date: 1978
- Language: English
- Type: Article
- Identifier: vital:6350 , http://hdl.handle.net/10962/d1006032
- Description: The blanching activities and hence bioavailabilities of the cream, ointment and fatty ointment preparations of Nerisone and Temetex (diflucortolone valerate 0.1%) were evaluated using an occluded and unoccluded blanching assay. These products were compared to Synalar ointment and cream (fluocinolone acetonide 0.025%), established topical corticosteroid preparations. Statistical analysis showed no significant differences between similar formulations of diflucortolone valerate. Significant differences were noted between diflucortolone valerate and fluocinolone acetonide preparations.
- Full Text:
- Date Issued: 1978
- Authors: Coleman, Gerald L , Kanfer, Isadore , Haigh, John M
- Date: 1978
- Language: English
- Type: Article
- Identifier: vital:6350 , http://hdl.handle.net/10962/d1006032
- Description: The blanching activities and hence bioavailabilities of the cream, ointment and fatty ointment preparations of Nerisone and Temetex (diflucortolone valerate 0.1%) were evaluated using an occluded and unoccluded blanching assay. These products were compared to Synalar ointment and cream (fluocinolone acetonide 0.025%), established topical corticosteroid preparations. Statistical analysis showed no significant differences between similar formulations of diflucortolone valerate. Significant differences were noted between diflucortolone valerate and fluocinolone acetonide preparations.
- Full Text:
- Date Issued: 1978
Comparative blanching activities of some topical corticosteroid containing lotions
- Meyer, I, Kanfer, Isadore, Haigh, John M
- Authors: Meyer, I , Kanfer, Isadore , Haigh, John M
- Date: 1981
- Language: English
- Type: Article
- Identifier: vital:6398 , http://hdl.handle.net/10962/d1006324
- Description: The blanching activities of Betnovate and Celestoderm-V lotions (betamethasone-17-valerate, 0,1%) and Diprosone lotion (betamethasone dipropionate, 0,55%) were determined by measuring their ability to cause blanching of human skin after topical application. Betnovate and Celestoderm-V lotions produced almost identical blanching profiles. Diprosone lotion displayed a statistically significant superior blanching acitivity over both Betnovate and Celestoderm-V lotions over the whole timespan of the trial.
- Full Text:
- Date Issued: 1981
- Authors: Meyer, I , Kanfer, Isadore , Haigh, John M
- Date: 1981
- Language: English
- Type: Article
- Identifier: vital:6398 , http://hdl.handle.net/10962/d1006324
- Description: The blanching activities of Betnovate and Celestoderm-V lotions (betamethasone-17-valerate, 0,1%) and Diprosone lotion (betamethasone dipropionate, 0,55%) were determined by measuring their ability to cause blanching of human skin after topical application. Betnovate and Celestoderm-V lotions produced almost identical blanching profiles. Diprosone lotion displayed a statistically significant superior blanching acitivity over both Betnovate and Celestoderm-V lotions over the whole timespan of the trial.
- Full Text:
- Date Issued: 1981
Comparison of the blanching activities of Dermovate, Betnovate and Eumovate creams and ointments
- Meyer, Eric, Magnus, Ashley D, Haigh, John M, Kanfer, Isadore
- Authors: Meyer, Eric , Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1988
- Language: English
- Type: Article
- Identifier: vital:6393 , http://hdl.handle.net/10962/d1006315
- Description: The human skin blanching assay was used to determine the blanching activities of Dermovate, Betnovate and Eumovate creams and ointments. Dermovate was found to elicit a superior blanching response to Betnovate which in turn elicited a superior blanching response to Eumovate, except in the comparison of Betnovate and Eumovate ointments under occlusion. The importance of employing the correct methodology of the blanching assay is emphasized and the good correlation between the results of this study and clinical trials is indicated.
- Full Text: false
- Date Issued: 1988
- Authors: Meyer, Eric , Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1988
- Language: English
- Type: Article
- Identifier: vital:6393 , http://hdl.handle.net/10962/d1006315
- Description: The human skin blanching assay was used to determine the blanching activities of Dermovate, Betnovate and Eumovate creams and ointments. Dermovate was found to elicit a superior blanching response to Betnovate which in turn elicited a superior blanching response to Eumovate, except in the comparison of Betnovate and Eumovate ointments under occlusion. The importance of employing the correct methodology of the blanching assay is emphasized and the good correlation between the results of this study and clinical trials is indicated.
- Full Text: false
- Date Issued: 1988
Comparison of visual CR-200 and CR-300 chromameter data obtained from the corticosteroid-induced skin-blanching assay
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper , text
- Identifier: vital:6344 , http://hdl.handle.net/10962/d1006611
- Description: 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.
- Full Text:
- Date Issued: 1998
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper , text
- Identifier: vital:6344 , http://hdl.handle.net/10962/d1006611
- Description: 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.
- Full Text:
- Date Issued: 1998
Complexes of mercury(II) and zinc(II) with primary aromatic amines
- Haigh, John M, Van Dam, M A, Thornton, D A
- Authors: Haigh, John M , Van Dam, M A , Thornton, D A
- Date: 1967
- Language: English
- Type: text , Article
- Identifier: vital:6370 , http://hdl.handle.net/10962/d1006072
- Description: A series of amine complexes has been prepared by reaction of zinc chloride and mercuric chloride with primary aromatic amines. A detailed assignment of the bands in the infra-red spectra of the complexes in the range 4000-625 cm [superscript]-1 is presented. The symmetric and asymmetric N-H stretching frequencies follow the relationship v(sym) = 345.5+ 0.876v(asym). The C-N stretching frequencies exhibit a linear relationship with the Hammett α-functions for the m- and p-substituted amines.
- Full Text:
- Date Issued: 1967
- Authors: Haigh, John M , Van Dam, M A , Thornton, D A
- Date: 1967
- Language: English
- Type: text , Article
- Identifier: vital:6370 , http://hdl.handle.net/10962/d1006072
- Description: A series of amine complexes has been prepared by reaction of zinc chloride and mercuric chloride with primary aromatic amines. A detailed assignment of the bands in the infra-red spectra of the complexes in the range 4000-625 cm [superscript]-1 is presented. The symmetric and asymmetric N-H stretching frequencies follow the relationship v(sym) = 345.5+ 0.876v(asym). The C-N stretching frequencies exhibit a linear relationship with the Hammett α-functions for the m- and p-substituted amines.
- Full Text:
- Date Issued: 1967