Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioeqivalence testing [authors' reply in Letters to the Editor]
- Smith, Eric W, Walker, Roderick B, Haigh, John M, Kanfer, Isadore
- Authors: Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6423 , http://hdl.handle.net/10962/d1006558
- Description: Reply to: Letter to the Editor by Singh GJ; Fleischer N; Lesko L; Williams R - relating to original article in Pharmaceutical Research (USA), Mar 1997, vol. 14, pp. 303-308.
- Full Text: false
- Date Issued: 1998
- Authors: Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6423 , http://hdl.handle.net/10962/d1006558
- Description: Reply to: Letter to the Editor by Singh GJ; Fleischer N; Lesko L; Williams R - relating to original article in Pharmaceutical Research (USA), Mar 1997, vol. 14, pp. 303-308.
- Full Text: false
- Date Issued: 1998
Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioequivalence testing
- Demana, Patrick H, Smith, Eric W, Walker, Roderick B, Haigh, John M, Kanfer, Isadore
- Authors: Demana, Patrick H , Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: Article
- Identifier: vital:6356 , http://hdl.handle.net/10962/d1006047
- Description: The American FDA has recently released a Guidance document for topical corticosteroid bioequivalence testing. The purpose of this study was to evaluate the recommendations of this document for appropriateness. The new specifications require a dose-vasoconstriction response estimation by the use of a Minolta chromameter in a preliminary pilot study to determine the parameters for use in a pivotal bioequivalence study. Methods. The visually-assessed human skin blanching assay methodology routinely practiced in our laboratories was modified to comply with the requirements of the pilot study so that visual and chromameter data could be compared. Two different cream formulations, each containing 0.12% betamethasone 17-valerate, were used for this comparison. Results. Visual data showed the expected rank order of AUC values for most dose durations whereas the chromameter data did not show similar results. The expected rank order of AUC values for both chromameter and visual data was not observed at very short dose durations. In fitting the data to pharmacodynamic models, equivalent goodness of fit criteria were obtained when several different parameter estimates were used in the model definition, however the visual data were best described by the sigmoid E[subscript max] model while the chromameter data were best described by the simple E[subscript max] model. Conclusions. The E[subscript max] values predicted by the models were close to the observed values for both data sets and, in addition, excellent correlation between the AUC values and the maximum blanching response (R[subscript max]) (r > 0.95) was noted for both methods of assessment. The chromameter ED[subscript 50] values determined in this study were approximately 2 hours for both preparations. At this dose duration the instrument would not be sensitive enough to distinguish between weak blanching responses and normal skin for bioequivalence assessment purposes.
- Full Text: false
- Date Issued: 1997
- Authors: Demana, Patrick H , Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: Article
- Identifier: vital:6356 , http://hdl.handle.net/10962/d1006047
- Description: The American FDA has recently released a Guidance document for topical corticosteroid bioequivalence testing. The purpose of this study was to evaluate the recommendations of this document for appropriateness. The new specifications require a dose-vasoconstriction response estimation by the use of a Minolta chromameter in a preliminary pilot study to determine the parameters for use in a pivotal bioequivalence study. Methods. The visually-assessed human skin blanching assay methodology routinely practiced in our laboratories was modified to comply with the requirements of the pilot study so that visual and chromameter data could be compared. Two different cream formulations, each containing 0.12% betamethasone 17-valerate, were used for this comparison. Results. Visual data showed the expected rank order of AUC values for most dose durations whereas the chromameter data did not show similar results. The expected rank order of AUC values for both chromameter and visual data was not observed at very short dose durations. In fitting the data to pharmacodynamic models, equivalent goodness of fit criteria were obtained when several different parameter estimates were used in the model definition, however the visual data were best described by the sigmoid E[subscript max] model while the chromameter data were best described by the simple E[subscript max] model. Conclusions. The E[subscript max] values predicted by the models were close to the observed values for both data sets and, in addition, excellent correlation between the AUC values and the maximum blanching response (R[subscript max]) (r > 0.95) was noted for both methods of assessment. The chromameter ED[subscript 50] values determined in this study were approximately 2 hours for both preparations. At this dose duration the instrument would not be sensitive enough to distinguish between weak blanching responses and normal skin for bioequivalence assessment purposes.
- Full Text: false
- Date Issued: 1997
The human skin blanching assay for in vivo topical corticosteroid assessment. II. Subject- and observer-dependent variation in blanching responses
- Haigh, John M, Meyer, Eric, Smith, Eric W, Kanfer, Isadore
- Authors: Haigh, John M , Meyer, Eric , Smith, Eric W , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: text , Article
- Identifier: vital:6382 , http://hdl.handle.net/10962/d1006300
- Description: The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective.
- Full Text:
- Date Issued: 1997
- Authors: Haigh, John M , Meyer, Eric , Smith, Eric W , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: text , Article
- Identifier: vital:6382 , http://hdl.handle.net/10962/d1006300
- Description: The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective.
- Full Text:
- Date Issued: 1997
The human skin-blanching assay for in vitro topical corticosteroid assessment. I. Reproducibility of the assay
- Haigh, John M, Meyer, Eric, Smith, Eric W, Kanfer, Isadore
- Authors: Haigh, John M , Meyer, Eric , Smith, Eric W , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: text , Article
- Identifier: vital:6381 , http://hdl.handle.net/10962/d1006299
- Description: The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective.
- Full Text:
- Date Issued: 1997
- Authors: Haigh, John M , Meyer, Eric , Smith, Eric W , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: text , Article
- Identifier: vital:6381 , http://hdl.handle.net/10962/d1006299
- Description: The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective.
- Full Text:
- Date Issued: 1997
Potency ranking of two new topical corticosteroid creams containing 0.1% desonide or 0.05% halometasone utilizing the human skin-blanching assay
- Meyer, Eric, Smith, Eric W, Haigh, John M, Kanfer, Isadore
- Authors: Meyer, Eric , Smith, Eric W , Haigh, John M , Kanfer, Isadore
- Date: 1988
- Language: English
- Type: Article
- Identifier: vital:6400 , http://hdl.handle.net/10962/d1006327
- Description: The human blanching assay was used to assess the potency of two new proprietary corticosteroid creams. The blanching abilities of 0.1% desonide cream and 0.05% halometasone cream were evaluated relative to the blanching elicited by 0.05% clobetasol 17-propionate cream, 0.1% betamethasone 17-valerate cream and 0.05% clobetasone 17-butyrate cream. The results of the trial indicated that the 0.1% desonide cream falls into the potent group of topical corticosteroid preparations and the 0.05% halomethasone cream falls into the moderately potent group.
- Full Text:
- Date Issued: 1988
- Authors: Meyer, Eric , Smith, Eric W , Haigh, John M , Kanfer, Isadore
- Date: 1988
- Language: English
- Type: Article
- Identifier: vital:6400 , http://hdl.handle.net/10962/d1006327
- Description: The human blanching assay was used to assess the potency of two new proprietary corticosteroid creams. The blanching abilities of 0.1% desonide cream and 0.05% halometasone cream were evaluated relative to the blanching elicited by 0.05% clobetasol 17-propionate cream, 0.1% betamethasone 17-valerate cream and 0.05% clobetasone 17-butyrate cream. The results of the trial indicated that the 0.1% desonide cream falls into the potent group of topical corticosteroid preparations and the 0.05% halomethasone cream falls into the moderately potent group.
- Full Text:
- Date Issued: 1988
Reply to correspondence: P.M. Gaylarde (1986) The human skin blanching assay—use and abuse
- Haigh, John M, Kanfer, Isadore, Meyer, Eric, Smith, Eric W
- Authors: Haigh, John M , Kanfer, Isadore , Meyer, Eric , Smith, Eric W
- Date: 1986
- Language: English
- Type: Article
- Identifier: vital:6376 , http://hdl.handle.net/10962/d1006293
- Description: Finally, we would like to assure Dr Gaylarde that we do not advocate the use of the human skin blanching assay. There are several other in vivo methods for determining corticosteroid activity which will provide equally meaningful results. What we are advocating is that if the human skin blanching assay is going to be used, then it should be used properly.
- Full Text:
- Date Issued: 1986
- Authors: Haigh, John M , Kanfer, Isadore , Meyer, Eric , Smith, Eric W
- Date: 1986
- Language: English
- Type: Article
- Identifier: vital:6376 , http://hdl.handle.net/10962/d1006293
- Description: Finally, we would like to assure Dr Gaylarde that we do not advocate the use of the human skin blanching assay. There are several other in vivo methods for determining corticosteroid activity which will provide equally meaningful results. What we are advocating is that if the human skin blanching assay is going to be used, then it should be used properly.
- Full Text:
- Date Issued: 1986
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
Relative potencies of topical corticosteroid formulations
- Haigh, John M, Kanfer, Isadore, Meyer, Eric, Smith, Eric W
- Authors: Haigh, John M , Kanfer, Isadore , Meyer, Eric , Smith, Eric W
- Date: 1985
- Language: English
- Type: Article
- Identifier: vital:6375 , http://hdl.handle.net/10962/d1006291
- Description: It seems to us, and others (Burdick, 1974), that multiple reading times are essential to produce the response-time profile. Comparisons of potencies of topical corticosteroid formulations should only be made on the basis of area under the curve measurements and statistical treatment of all values obtained at each reading time throughout the course of the experiment.
- Full Text:
- Date Issued: 1985
- Authors: Haigh, John M , Kanfer, Isadore , Meyer, Eric , Smith, Eric W
- Date: 1985
- Language: English
- Type: Article
- Identifier: vital:6375 , http://hdl.handle.net/10962/d1006291
- Description: It seems to us, and others (Burdick, 1974), that multiple reading times are essential to produce the response-time profile. Comparisons of potencies of topical corticosteroid formulations should only be made on the basis of area under the curve measurements and statistical treatment of all values obtained at each reading time throughout the course of the experiment.
- Full Text:
- Date Issued: 1985
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