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
Determination of erythromycin in serum and urine by high performance liquid chromatography with ultraviolet detection
- Stubbs, Christopher, Haigh, John M, Kanfer, Isadore
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1985
- Language: English
- Type: text , Article
- Identifier: vital:6428 , http://hdl.handle.net/10962/d1006576
- Description: A high-performance liquid chromatographic analysis of erythromycin in human serum and urine with UV detection at 200 nm is presented. The method involves a solid-phase extraction procedure followed by a simple phase separation step and chromatography on a reversed-phase column. The method has sensitivity limits of 0.25 and 1.0 g/mL in serum and urine, respectively, and is sufficiently sensitive to monitor concentrations of erythromycin in human serum and urine after the administration of a single 500-mg erythromycin stearate tablet.
- Full Text:
- Date Issued: 1985
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1985
- Language: English
- Type: text , Article
- Identifier: vital:6428 , http://hdl.handle.net/10962/d1006576
- Description: A high-performance liquid chromatographic analysis of erythromycin in human serum and urine with UV detection at 200 nm is presented. The method involves a solid-phase extraction procedure followed by a simple phase separation step and chromatography on a reversed-phase column. The method has sensitivity limits of 0.25 and 1.0 g/mL in serum and urine, respectively, and is sufficiently sensitive to monitor concentrations of erythromycin in human serum and urine after the administration of a single 500-mg erythromycin stearate tablet.
- Full Text:
- Date Issued: 1985
Precision of tristimulus chromameter results from corticosteroid-induced skin blanching
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6342 , http://hdl.handle.net/10962/d1006609
- Description: The human skin blanching (vasoconstriction) assay has been in use for 3 decades as a tool for the assessment of the release of corticosteroids from topical dosage forms. Application of corticosteroids produces a whitening (blanching) of the skin, the intensity of which is directly related to the clinical efficacyof the formulation. Assessment of the intensity of the induced blanching has classically been, and continues to be, pe1fonned by visual grading, a method which has been criticised because of the subjectivenature of the assessment Recently there has been considerablediscussion in the literature regarding the use of the chromameter as an objective instrumental method of monitoring corticosteroid induced skin blanching for bioequivalence assessment purposes. The FDA has released a Guidance document recommending the use of the chromameter for this purpose. The chromameter measures colour in teims of three indices: the L-scale (light-dark), the a-scale (red-green) and the b-scale (yellow-blue).Any colour can be expressedabsolutelyin terms of these three values.The Guidance protocol suggests the use of only the a-scale values in quantifying the blanching response after correction of the data which includes subtraction of baseline and unmedicated site values. One of the unresolved issues in the FDA Guidance document is this method of data manipulation suggested since the instrument should be capable of assigning an absolute colour value to each site during the vasoconstriction period. The purpose of this study was to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriatenessof these suggested procedures.
- Full Text:
- Date Issued: 1998
- Authors: Smith, Eric W , Haigh, John M
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6342 , http://hdl.handle.net/10962/d1006609
- Description: The human skin blanching (vasoconstriction) assay has been in use for 3 decades as a tool for the assessment of the release of corticosteroids from topical dosage forms. Application of corticosteroids produces a whitening (blanching) of the skin, the intensity of which is directly related to the clinical efficacyof the formulation. Assessment of the intensity of the induced blanching has classically been, and continues to be, pe1fonned by visual grading, a method which has been criticised because of the subjectivenature of the assessment Recently there has been considerablediscussion in the literature regarding the use of the chromameter as an objective instrumental method of monitoring corticosteroid induced skin blanching for bioequivalence assessment purposes. The FDA has released a Guidance document recommending the use of the chromameter for this purpose. The chromameter measures colour in teims of three indices: the L-scale (light-dark), the a-scale (red-green) and the b-scale (yellow-blue).Any colour can be expressedabsolutelyin terms of these three values.The Guidance protocol suggests the use of only the a-scale values in quantifying the blanching response after correction of the data which includes subtraction of baseline and unmedicated site values. One of the unresolved issues in the FDA Guidance document is this method of data manipulation suggested since the instrument should be capable of assigning an absolute colour value to each site during the vasoconstriction period. The purpose of this study was to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriatenessof these suggested procedures.
- Full Text:
- Date Issued: 1998
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
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
The registration of generic topical corticosteroid formulations in South Africa: a report
- Haigh, John M, Smith, Eric W
- Authors: Haigh, John M , Smith, Eric W
- Date: 2002
- Language: English
- Type: Article
- Identifier: vital:6368 , http://hdl.handle.net/10962/d1006068
- Description: [From the text]Topical corticosteroid formulations are used widely for a variety of skin conditions such as psoriasis and eczema. The most commonly used formulation types are cream, ointment, lotion and scalp application, with some mousse formulations being released recently onto the market for scalp application. The type of formulation used depends on the condition being treated. Dry lesions are normally treated with ointments and wet lesions with creams. Cosmetically, cream formulations are more acceptable as they can be rubbed in, thus leaving no residual oiliness. Scalp applications have to be less viscous to allow the formulation to pass through the hair and contact the scalp. Occlusion with plastic wrapping hydrates the stratum corneum and facilitates the passage of the corticosteroid through this barrier to the basal layer where the therapeutic effect is required.
- Full Text:
- Date Issued: 2002
- Authors: Haigh, John M , Smith, Eric W
- Date: 2002
- Language: English
- Type: Article
- Identifier: vital:6368 , http://hdl.handle.net/10962/d1006068
- Description: [From the text]Topical corticosteroid formulations are used widely for a variety of skin conditions such as psoriasis and eczema. The most commonly used formulation types are cream, ointment, lotion and scalp application, with some mousse formulations being released recently onto the market for scalp application. The type of formulation used depends on the condition being treated. Dry lesions are normally treated with ointments and wet lesions with creams. Cosmetically, cream formulations are more acceptable as they can be rubbed in, thus leaving no residual oiliness. Scalp applications have to be less viscous to allow the formulation to pass through the hair and contact the scalp. Occlusion with plastic wrapping hydrates the stratum corneum and facilitates the passage of the corticosteroid through this barrier to the basal layer where the therapeutic effect is required.
- Full Text:
- Date Issued: 2002
New developments in the methodology available for the assessment of topical corticosteroid-induced skin blanching
- Haigh, John M, Smith, Eric W, Maibach, Howard I
- Authors: Haigh, John M , Smith, Eric W , Maibach, Howard I
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6384 , http://hdl.handle.net/10962/d1006305
- Description: Since the publication of the previous edition of this book there have been considerable developments and controversy in the field of topical corticosteroid bioequivalence assessment. There has been considerable discussion in the literature concerning the use of the Minolta chromameter for the measurement of corticosteroid-induced skin blanching, as it is believed this instrument would produce more objective results than the visual grading procedure. These efforts culminated in the release of a guidance document from the Food and Drug Administration (FDA) detailing the procedures to be followed for the determination of topical corticosteroid bioequivalence using the chromameter. Since the promulgation of this document there have been challenges on the validity and scientific merit of the documented procedures, and recently the FDA itself conceded that it may be necessary to redefine some of the protocol evaluations. This chapter attempts to redefine the current standing of the two methods of response assessment.
- Full Text:
- Date Issued: 1998
- Authors: Haigh, John M , Smith, Eric W , Maibach, Howard I
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6384 , http://hdl.handle.net/10962/d1006305
- Description: Since the publication of the previous edition of this book there have been considerable developments and controversy in the field of topical corticosteroid bioequivalence assessment. There has been considerable discussion in the literature concerning the use of the Minolta chromameter for the measurement of corticosteroid-induced skin blanching, as it is believed this instrument would produce more objective results than the visual grading procedure. These efforts culminated in the release of a guidance document from the Food and Drug Administration (FDA) detailing the procedures to be followed for the determination of topical corticosteroid bioequivalence using the chromameter. Since the promulgation of this document there have been challenges on the validity and scientific merit of the documented procedures, and recently the FDA itself conceded that it may be necessary to redefine some of the protocol evaluations. This chapter attempts to redefine the current standing of the two methods of response assessment.
- Full Text:
- Date Issued: 1998
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
The effects of elevated and ambient temperature conditions on dilutions of fluocinolone acetonide ointment assessed using the human skin-blanching assay
- Haigh, John M, Smith, Eric W
- Authors: Haigh, John M , Smith, Eric W
- Date: 1995
- Language: English
- Type: text , Article
- Identifier: vital:6380 , http://hdl.handle.net/10962/d1006298
- Description: Topical corticosteroid formulations have been in use now for some 30 years and many methods are available for the in vivo assessment of these preparations. Of all the assays described in the literature, the one first advocated by McKenzie and Stoughton, the so-called vasoconstrictor assay, is one of the most reliable if performed by experienced researchers using - the optimised methodology. Topical application of corticosteroids produces a whitening (blanching) of the skin, the intensity of which is directly proportional to the clinical efficacy of the formulation. Assessment of the degree of blanching produced is therefore of use in determining the rate and extent of corticosteroid release' from the semi-solid base through the stratum corneum. Since it is the degree of blanching which is measured, we prefer to call this test the human skin blanching assay. Some of the main advantages of this assay technique are that normal healthy skin is used therefore persons with dermatological complaints are not compromised, it is not painful for the volunteers, it is non-invasive and several formulations can be evaluated simultaneously. Most commercially available topical corticosteroid preparations have been formulated in such a way as to provide optimum release of the active ingredient from the base through the stratum corneum. Despite this fact, many practitioners often prescribe dilutions of topical corticosteroid formulations, presumably in an effort to reduce the unwanted side effects. This could be problematic; dilution with an incompatible base could destroy the delivery environment thus considerably reducing the efficacy of the formulation. The method of dilution could also play a role in the suitability of the final preparation. The objective of this work was to determine the effects of two different dilutions of fluocinolone ointment at both ambient and elevated temperature on the blanching produced by the dilutions and, by inference, the relative clinical efficacies of these dilutions compared to the full strength product.
- Full Text:
- Date Issued: 1995
- Authors: Haigh, John M , Smith, Eric W
- Date: 1995
- Language: English
- Type: text , Article
- Identifier: vital:6380 , http://hdl.handle.net/10962/d1006298
- Description: Topical corticosteroid formulations have been in use now for some 30 years and many methods are available for the in vivo assessment of these preparations. Of all the assays described in the literature, the one first advocated by McKenzie and Stoughton, the so-called vasoconstrictor assay, is one of the most reliable if performed by experienced researchers using - the optimised methodology. Topical application of corticosteroids produces a whitening (blanching) of the skin, the intensity of which is directly proportional to the clinical efficacy of the formulation. Assessment of the degree of blanching produced is therefore of use in determining the rate and extent of corticosteroid release' from the semi-solid base through the stratum corneum. Since it is the degree of blanching which is measured, we prefer to call this test the human skin blanching assay. Some of the main advantages of this assay technique are that normal healthy skin is used therefore persons with dermatological complaints are not compromised, it is not painful for the volunteers, it is non-invasive and several formulations can be evaluated simultaneously. Most commercially available topical corticosteroid preparations have been formulated in such a way as to provide optimum release of the active ingredient from the base through the stratum corneum. Despite this fact, many practitioners often prescribe dilutions of topical corticosteroid formulations, presumably in an effort to reduce the unwanted side effects. This could be problematic; dilution with an incompatible base could destroy the delivery environment thus considerably reducing the efficacy of the formulation. The method of dilution could also play a role in the suitability of the final preparation. The objective of this work was to determine the effects of two different dilutions of fluocinolone ointment at both ambient and elevated temperature on the blanching produced by the dilutions and, by inference, the relative clinical efficacies of these dilutions compared to the full strength product.
- Full Text:
- Date Issued: 1995
The structure of aliphatic amine adducts of uranyl acetylacetonate. III. Dioxobis(2,4-pentanedionato)mono (2-N-isopropylaminopentan-4-one)uranium(VI)
- Rodgers, A L, Nassimbeni, L R, Haigh, John M
- Authors: Rodgers, A L , Nassimbeni, L R , Haigh, John M
- Date: 1977
- Language: English
- Type: text , Article
- Identifier: vital:6419 , http://hdl.handle.net/10962/d1006552
- Description: Introduction: In two earlier structural determinations of compounds of this type we have shown that the conformation of the adduct moiety is dependent on the formation of intramolecular N-H...0 hydrogen bonds (part I: Haigh, Nassimbeni, Pauptit, Rodgers & Sheldrick, 1976; part II: Nassimbeni, Orpen, Pauptit, Rodgers & Haigh, 1977). We have carried out the present analysis to study the conformational effects on the ligand brought about by the steric influence of an isopropyl substituent at N.
- Full Text:
- Date Issued: 1977
- Authors: Rodgers, A L , Nassimbeni, L R , Haigh, John M
- Date: 1977
- Language: English
- Type: text , Article
- Identifier: vital:6419 , http://hdl.handle.net/10962/d1006552
- Description: Introduction: In two earlier structural determinations of compounds of this type we have shown that the conformation of the adduct moiety is dependent on the formation of intramolecular N-H...0 hydrogen bonds (part I: Haigh, Nassimbeni, Pauptit, Rodgers & Sheldrick, 1976; part II: Nassimbeni, Orpen, Pauptit, Rodgers & Haigh, 1977). We have carried out the present analysis to study the conformational effects on the ligand brought about by the steric influence of an isopropyl substituent at N.
- Full Text:
- Date Issued: 1977
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
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
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
High performance liquid chromatographic analysis of oleandomycin in serum and urine
- Stubbs, Christopher, Haigh, John M, Kanfer, Isadore
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1986
- Language: English
- Type: text , Article
- Identifier: vital:6429 , http://hdl.handle.net/10962/d1006590
- Description: The determination of oleandomycin in serum and urine by high-performance liquid chromatography using erythromycin as internal standard is described. The separation was achieved on a reversed-phase C 1 s column employing acetonitrile-0.05 A4 phosphate buffer (30:70), adjusted to pH 7.0, as the mobile phase with UV detection at 200 nm. A solid-phase extraction procedure, combined with a simple phaseseparation step was used prior to chromatographic analysis. Linear calibration curves were obtained in the concentration ranges 0.25-5.0 pg/ml (serum) and 1 .O-25.0 pg/ml (urine). Precise quantitative analysis has been achieved at these levels with relative standard deviations of < 5%.
- Full Text:
- Date Issued: 1986
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1986
- Language: English
- Type: text , Article
- Identifier: vital:6429 , http://hdl.handle.net/10962/d1006590
- Description: The determination of oleandomycin in serum and urine by high-performance liquid chromatography using erythromycin as internal standard is described. The separation was achieved on a reversed-phase C 1 s column employing acetonitrile-0.05 A4 phosphate buffer (30:70), adjusted to pH 7.0, as the mobile phase with UV detection at 200 nm. A solid-phase extraction procedure, combined with a simple phaseseparation step was used prior to chromatographic analysis. Linear calibration curves were obtained in the concentration ranges 0.25-5.0 pg/ml (serum) and 1 .O-25.0 pg/ml (urine). Precise quantitative analysis has been achieved at these levels with relative standard deviations of < 5%.
- Full Text:
- Date Issued: 1986
The release of betamethasone 17-valerate from extemporaneous dilutions of a proprietary topical cream
- Magnus, Ashley D, Haigh, John M, Kanfer, Isadore
- Authors: Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1981
- Language: English
- Type: Article
- Identifier: vital:6397 , http://hdl.handle.net/10962/d1006322
- Description: Six different vehicles for topical use were used to prepare 50% dilutions of Betnovate@ (betamethasone 17-valerate, 0.1 %) cream. Blanching assessment was undertaken immediately after preparing the various dilutions and at 1 and 3 months thereafter. Few statistically significant differences were noted between any of the preparations tested indicating that the rate of release of betamethasone 17-valerate is relatively unaffected by dilution. All preparations were assayed by a stability indicating high pressure liquid chromatographic technique for corticosteroid content. A diminution in the content of betamethasone 17-valerate in the E45 dilution was found 14 months after preparation. All other formulations tested were found to comply with label claim specifications.
- Full Text:
- Date Issued: 1981
- Authors: Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1981
- Language: English
- Type: Article
- Identifier: vital:6397 , http://hdl.handle.net/10962/d1006322
- Description: Six different vehicles for topical use were used to prepare 50% dilutions of Betnovate@ (betamethasone 17-valerate, 0.1 %) cream. Blanching assessment was undertaken immediately after preparing the various dilutions and at 1 and 3 months thereafter. Few statistically significant differences were noted between any of the preparations tested indicating that the rate of release of betamethasone 17-valerate is relatively unaffected by dilution. All preparations were assayed by a stability indicating high pressure liquid chromatographic technique for corticosteroid content. A diminution in the content of betamethasone 17-valerate in the E45 dilution was found 14 months after preparation. All other formulations tested were found to comply with label claim specifications.
- Full Text:
- Date Issued: 1981
Complexes of zinc, cadmium and mercury 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: Article
- Identifier: vital:6369 , http://hdl.handle.net/10962/d1006070
- Description: We have examined the infrared spectra of thirty-seven complexes derived from the reaction of zinc chloride, mercuric chloride and cadmium chloride, bromide and iodide with several primary aromatic amines. The object of the study was to ascertain whether the frequency data would shed light on the mechanisms of metal-donor atom bonding and electron shifts within the molecules and, in the case of the cadmium complexes, in order to obtain evidence for the transmission of electronic effects through a cadmium atom.
- Full Text:
- Date Issued: 1967
- Authors: Haigh, John M , Van Dam, M A , Thornton, D A
- Date: 1967
- Language: English
- Type: Article
- Identifier: vital:6369 , http://hdl.handle.net/10962/d1006070
- Description: We have examined the infrared spectra of thirty-seven complexes derived from the reaction of zinc chloride, mercuric chloride and cadmium chloride, bromide and iodide with several primary aromatic amines. The object of the study was to ascertain whether the frequency data would shed light on the mechanisms of metal-donor atom bonding and electron shifts within the molecules and, in the case of the cadmium complexes, in order to obtain evidence for the transmission of electronic effects through a cadmium atom.
- Full Text:
- Date Issued: 1967
Ranking of topical corticosteroids: principles and results
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1993
- Language: English
- Type: text , Article
- Identifier: vital:6434 , http://hdl.handle.net/10962/d1006607
- Description: The increasing synthesis and use of topical corticosteroid products over the past 30 years has necessitated the development of suitable methods for evaluating the efficacy and potency of new drug entities. Several in vivo models have been developed in this regard using laboratory animals and human subjects. Generally, these tests measure the difference in the non-immunological inflammatory response to an exogenous inflammatory mediator in the presence and absence of the corticosteroid under test. There are also immunologically based assays and several tests which assess the anti proliferative effects of the drug. Several comparative disease model evaluations have also been developed using human subjects. Most of these assays are non-ideal from one point of view or another: most are invasive methods which require some form of trauma to be induced in the skin and therefore problematic to perform and monitor.
- Full Text:
- Date Issued: 1993
- Authors: Smith, Eric W , Haigh, John M
- Date: 1993
- Language: English
- Type: text , Article
- Identifier: vital:6434 , http://hdl.handle.net/10962/d1006607
- Description: The increasing synthesis and use of topical corticosteroid products over the past 30 years has necessitated the development of suitable methods for evaluating the efficacy and potency of new drug entities. Several in vivo models have been developed in this regard using laboratory animals and human subjects. Generally, these tests measure the difference in the non-immunological inflammatory response to an exogenous inflammatory mediator in the presence and absence of the corticosteroid under test. There are also immunologically based assays and several tests which assess the anti proliferative effects of the drug. Several comparative disease model evaluations have also been developed using human subjects. Most of these assays are non-ideal from one point of view or another: most are invasive methods which require some form of trauma to be induced in the skin and therefore problematic to perform and monitor.
- Full Text:
- Date Issued: 1993
In vitro-in vivo evaluation of a sustained release phenylpropanolamine oral dosage form
- Dowse, Roslind, Haigh, John M, Kanfer, Isadore
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1982
- Language: English
- Type: Article
- Identifier: vital:6360 , http://hdl.handle.net/10962/d1006052
- Description: There is increasing interest in measuring pharmacokinetic parameters of phenylpropanolamine (PPA), a sympathomimetic amine used in over-the-counter nasal decongestants and anorectic formulations. A high pressure liquid chromatographic (HPLC) procedure was developed to enable direct ultraviolet detection of PPA, after extraction from serum and urine, without prior derivatization of the drug. This method was used to assay samples obtained from a bioavailability study of BUBtained-releasePPA tablets. The mean serum and urine profiles obtained are presented. The sustained-release tablets were subjected to dissolution testing utilizing the United States Pharmacopoeia (USP XIX) rotating basket method. An internal standard was incorporated into the dissolution fluid to enable direct analysis of the samples by HPLC. A comparison of three different dissolution fluid regimens was carried out to determine if release of the drug was affected by the change in pH of the medium and to select the most convenient method for the final dissolution studies. Some preliminary observations relating to correlations between rate of drug release from the sustained-release dosage form and percent drug absorbed are presented.
- Full Text:
- Date Issued: 1982
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1982
- Language: English
- Type: Article
- Identifier: vital:6360 , http://hdl.handle.net/10962/d1006052
- Description: There is increasing interest in measuring pharmacokinetic parameters of phenylpropanolamine (PPA), a sympathomimetic amine used in over-the-counter nasal decongestants and anorectic formulations. A high pressure liquid chromatographic (HPLC) procedure was developed to enable direct ultraviolet detection of PPA, after extraction from serum and urine, without prior derivatization of the drug. This method was used to assay samples obtained from a bioavailability study of BUBtained-releasePPA tablets. The mean serum and urine profiles obtained are presented. The sustained-release tablets were subjected to dissolution testing utilizing the United States Pharmacopoeia (USP XIX) rotating basket method. An internal standard was incorporated into the dissolution fluid to enable direct analysis of the samples by HPLC. A comparison of three different dissolution fluid regimens was carried out to determine if release of the drug was affected by the change in pH of the medium and to select the most convenient method for the final dissolution studies. Some preliminary observations relating to correlations between rate of drug release from the sustained-release dosage form and percent drug absorbed are presented.
- Full Text:
- Date Issued: 1982
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
In vitro systems for the assessment of drug release from topical formulations and trans-membrane permeation
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6441 , http://hdl.handle.net/10962/d1006628
- Description: Numerous experimental methods have been developed to investigate drug release from vehicles and the percutaneous absorption of topically applied chemicals. The objective of this research is often to find correlation between laboratory results and the transdermal absorption experienced by living subjects so that in vivo experimentation may be curtailed. In many instances, the diverse experimental techniques tend to obscure absorption-controlling factors and complicate inter study comparisons, rather than clarify the complex transdermal absorption process. Moreover, lack of agreement between results may occasionally be ascribed to shortcomings in the in vitro methodology employed. The benefits of using an in vitro cell system for the preliminary testing of drug permeation in the laboratory are obvious. The environmental and diffusion variables may be controlled in an attempt to elucidate specific factors affecting the kinetic processes and drug bioavailability. Investigations are complex because of the multiple, interrelated events underlying the processes of drug partitioning from the applied vehicle and diffusion through the portals of the stratum corneum to the myriad of metabolic, binding, and clearance activities in the lower epidermal and dermal strata.
- Full Text:
- Date Issued: 1989
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: Book chapter
- Identifier: vital:6441 , http://hdl.handle.net/10962/d1006628
- Description: Numerous experimental methods have been developed to investigate drug release from vehicles and the percutaneous absorption of topically applied chemicals. The objective of this research is often to find correlation between laboratory results and the transdermal absorption experienced by living subjects so that in vivo experimentation may be curtailed. In many instances, the diverse experimental techniques tend to obscure absorption-controlling factors and complicate inter study comparisons, rather than clarify the complex transdermal absorption process. Moreover, lack of agreement between results may occasionally be ascribed to shortcomings in the in vitro methodology employed. The benefits of using an in vitro cell system for the preliminary testing of drug permeation in the laboratory are obvious. The environmental and diffusion variables may be controlled in an attempt to elucidate specific factors affecting the kinetic processes and drug bioavailability. Investigations are complex because of the multiple, interrelated events underlying the processes of drug partitioning from the applied vehicle and diffusion through the portals of the stratum corneum to the myriad of metabolic, binding, and clearance activities in the lower epidermal and dermal strata.
- Full Text:
- Date Issued: 1989