The human skin-blanching assay for comparing topical corticosteroid availability
- Smith, Eric W, Meyer, Eric, Haigh, John M, Maibach, Harold I
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M , Maibach, Harold I
- Date: 1991
- Language: English
- Type: Article
- Identifier: vital:6433 , http://hdl.handle.net/10962/d1006604
- Description: The human skin blanching assay remains in widespread use as a reliable, qualitative, comparative indicator of topical corticosteroid availability and potency. The experimental refinements promulgated by certain researchers in this field have yielded a versatile bioassay for the accurate assessment of new drugs or delivery vehicles. With the increasing appearance of generic topical corticosteroid formulations which compete with trade-name equivalents, the vital importance of this assay in regulatory affairs and assessing bioequivalence has been re-emphasized. It is stressed that if the blanching assay is to be used in this sphere, then multiple-reading trials must be conducted; important registration or clinical decisions cannot be made with any validity from short-term assessments.
- Full Text:
- Authors: Smith, Eric W , Meyer, Eric , Haigh, John M , Maibach, Harold I
- Date: 1991
- Language: English
- Type: Article
- Identifier: vital:6433 , http://hdl.handle.net/10962/d1006604
- Description: The human skin blanching assay remains in widespread use as a reliable, qualitative, comparative indicator of topical corticosteroid availability and potency. The experimental refinements promulgated by certain researchers in this field have yielded a versatile bioassay for the accurate assessment of new drugs or delivery vehicles. With the increasing appearance of generic topical corticosteroid formulations which compete with trade-name equivalents, the vital importance of this assay in regulatory affairs and assessing bioequivalence has been re-emphasized. It is stressed that if the blanching assay is to be used in this sphere, then multiple-reading trials must be conducted; important registration or clinical decisions cannot be made with any validity from short-term assessments.
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Topical corticosteroid-induced skin blanching measurement, eye or instrument?
- Haigh, John M, Smith, Eric W
- Authors: Haigh, John M , Smith, Eric W
- Date: 1991
- Language: English
- Type: Article
- Identifier: vital:6378 , http://hdl.handle.net/10962/d1006296
- Description: We have read with interest a recent critique of the human skin blanching assay. We are concerned about the accuracy of statements and the interpretation of results presented in this publication. Having successfully employed this bioassay for over 15 years, and having noted similar, productive usage of this optimized technique reported from laboratories worldwide, the negativism expressed in the critique could dissuade potential researchers from employing this extremely useful assay procedure.
- Full Text:
- Authors: Haigh, John M , Smith, Eric W
- Date: 1991
- Language: English
- Type: Article
- Identifier: vital:6378 , http://hdl.handle.net/10962/d1006296
- Description: We have read with interest a recent critique of the human skin blanching assay. We are concerned about the accuracy of statements and the interpretation of results presented in this publication. Having successfully employed this bioassay for over 15 years, and having noted similar, productive usage of this optimized technique reported from laboratories worldwide, the negativism expressed in the critique could dissuade potential researchers from employing this extremely useful assay procedure.
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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:
- 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.
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In vitro diffusion cell design and validation. I. A stability-indicating high-performance liquid chromatographic assay for betamethasone 17-valerate in purified isopropyl myristate receptor phase
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: text , Article
- Identifier: vital:6431 , http://hdl.handle.net/10962/d1006595
- Description: Introduction: The development of a reliable in vitro permeation system necessitates the use of a precise and accurate method of quantifying the amount of permeant partitioning from the membrane into the cell receptor phase. Aqueous donor and receptor chamber fluids have been used in the majority of reported investigations, which makes quantitative permeant analysis relatively facile. Alternatively, radiolabelled diffusants have been used and flux rates monitored by scintillation counting, obviating the need for chromatographic separation of the receptor-phase components. However, this technique is not applicable when nonlabelled compounds or commercial dosage forms are to be evaluated by a cell system. Furthermore, several studies indicate that aqueous receptor phases may not present an optimal partitioning environment for certain lipophilic permeants (1-4), thereby impairing accurate flux monitoring due to limited diffusant solubility. Several attempts have therefore been made to improve the partitioning environment within these systems, by the addition of surfactants for example (4). A lipophilic receptor environment appears beneficial for corticosteroid partitioning, and thus, the use of isopropyl myristate has been investigated because of its bipolar properties that tend to mimic the biochemical composition of the skin (5,6). Betamethasone 17-valerate and its 21-valerate degradation product are highly soluble in isopropyl myristate and this nonaqueous solvent will not augment C-17-to-C-21 ester degradation reactions.
- Full Text:
- Authors: Smith, Eric W , Haigh, John M
- Date: 1989
- Language: English
- Type: text , Article
- Identifier: vital:6431 , http://hdl.handle.net/10962/d1006595
- Description: Introduction: The development of a reliable in vitro permeation system necessitates the use of a precise and accurate method of quantifying the amount of permeant partitioning from the membrane into the cell receptor phase. Aqueous donor and receptor chamber fluids have been used in the majority of reported investigations, which makes quantitative permeant analysis relatively facile. Alternatively, radiolabelled diffusants have been used and flux rates monitored by scintillation counting, obviating the need for chromatographic separation of the receptor-phase components. However, this technique is not applicable when nonlabelled compounds or commercial dosage forms are to be evaluated by a cell system. Furthermore, several studies indicate that aqueous receptor phases may not present an optimal partitioning environment for certain lipophilic permeants (1-4), thereby impairing accurate flux monitoring due to limited diffusant solubility. Several attempts have therefore been made to improve the partitioning environment within these systems, by the addition of surfactants for example (4). A lipophilic receptor environment appears beneficial for corticosteroid partitioning, and thus, the use of isopropyl myristate has been investigated because of its bipolar properties that tend to mimic the biochemical composition of the skin (5,6). Betamethasone 17-valerate and its 21-valerate degradation product are highly soluble in isopropyl myristate and this nonaqueous solvent will not augment C-17-to-C-21 ester degradation reactions.
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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
- 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
Dilution of topical corticosteroid formulations
- Authors: Haigh, John M
- Date: 1988
- Language: English
- Type: text , Article
- Identifier: vital:6377 , http://hdl.handle.net/10962/d1006295
- Description: It has been a long-held concern of a number of people working in this field that some dermatologists prescribing a 1:10 dilution of a corticosteroid preparation such as Dermovate cream believe that the final product will be one tenth as efficacious and also produce one tenth of the side effects as the undiluted formulation. This is certainly not the case. Dermovate falls into the very potent category of topical corticosteroid preparations (as defined in the United Kingdom Monthly Index of Medical Specialities) and a 1:10 dilution falls into the potent category.
- Full Text:
- Authors: Haigh, John M
- Date: 1988
- Language: English
- Type: text , Article
- Identifier: vital:6377 , http://hdl.handle.net/10962/d1006295
- Description: It has been a long-held concern of a number of people working in this field that some dermatologists prescribing a 1:10 dilution of a corticosteroid preparation such as Dermovate cream believe that the final product will be one tenth as efficacious and also produce one tenth of the side effects as the undiluted formulation. This is certainly not the case. Dermovate falls into the very potent category of topical corticosteroid preparations (as defined in the United Kingdom Monthly Index of Medical Specialities) and a 1:10 dilution falls into the potent category.
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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:
- 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.
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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:
- 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.
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Pharmacokinetics of phenylpropanolamine in humans after a single dose study
- Dowse, Roslind, Haigh, John M, Kanfer, Isadore
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6363 , http://hdl.handle.net/10962/d1006059
- Description: The pharmacokinetics of phenylpropanolamine have been studied in healthy human volunteers following the oral administration of an aqueous solution of the drug (50 mg/200 ml). Blood and urine samples collected throughout the trial were assayed using HPLC with UV detection. The drug was shown to be rapidly absorbed with a mean tmax of 1.47 ± 0.49 h and a mean elimination half-life of 4.0 ± 0.5 h. Phenylpropanolamine is predominantly excreted via the kidney with a mean renal clearance of 0.646 ± 0.089 liter/kg/h and 90.2 ± 1.7% excreted unchanged in the urine. The data were not well described using conventional one or two body compartment models. However, the incorporation of a discontinuous absorption phase into the models resulted in an improved overall fit with better characterisation of the absorption phase.
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- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6363 , http://hdl.handle.net/10962/d1006059
- Description: The pharmacokinetics of phenylpropanolamine have been studied in healthy human volunteers following the oral administration of an aqueous solution of the drug (50 mg/200 ml). Blood and urine samples collected throughout the trial were assayed using HPLC with UV detection. The drug was shown to be rapidly absorbed with a mean tmax of 1.47 ± 0.49 h and a mean elimination half-life of 4.0 ± 0.5 h. Phenylpropanolamine is predominantly excreted via the kidney with a mean renal clearance of 0.646 ± 0.089 liter/kg/h and 90.2 ± 1.7% excreted unchanged in the urine. The data were not well described using conventional one or two body compartment models. However, the incorporation of a discontinuous absorption phase into the models resulted in an improved overall fit with better characterisation of the absorption phase.
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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:
- 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%.
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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:
- 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.
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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:
- 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.
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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:
- 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.
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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:
- 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.
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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:
- 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.
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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:
- 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.
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Determination of phenylpropanolamine in serum and urine by high performance liquid chromatography
- Dowse, Roslind, Haigh, John M, Kanfer, Isadore
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6361 , http://hdl.handle.net/10962/d1006056
- Description: A high-performance liquid chromatographic analysis of phenylpropanolamine in human serum and urine without prior derivatization is presented. Using direct UV detection the method is sufficiently sensitive to detect 25 ng of drug/ml of serum or urine; the coefficients of variation at 25 ng/ml and 500 ng/ml were 5.16 and 2.12, respectively, in serum. The method involves serum and urine extraction at a basic pH with chloroform, a single back-extraction, and chromatography on a reverse-phase column. Serum and urine data following administration of a single 150-mg sustained-release tablet of phenylpropanolamine hydrochloride in 6 healthy volunteers demonstrates the suitability of the analytical method.
- Full Text:
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6361 , http://hdl.handle.net/10962/d1006056
- Description: A high-performance liquid chromatographic analysis of phenylpropanolamine in human serum and urine without prior derivatization is presented. Using direct UV detection the method is sufficiently sensitive to detect 25 ng of drug/ml of serum or urine; the coefficients of variation at 25 ng/ml and 500 ng/ml were 5.16 and 2.12, respectively, in serum. The method involves serum and urine extraction at a basic pH with chloroform, a single back-extraction, and chromatography on a reverse-phase column. Serum and urine data following administration of a single 150-mg sustained-release tablet of phenylpropanolamine hydrochloride in 6 healthy volunteers demonstrates the suitability of the analytical method.
- Full Text:
Phenylpropanolamine hydrochloride
- Kanfer, Isadore, Haigh, John M, Dowse, Roslind
- Authors: Kanfer, Isadore , Haigh, John M , Dowse, Roslind
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6385 , http://hdl.handle.net/10962/d1006306
- Description: Phenylpropanolamine hydrochloride belongs to the sympathomimetic amine class of drugs and is structurally related to ephedrine hydrochloride. Its synthesis was first reported in 1910 and the first American patent was registered in 1939. The effects of phenylpropanolamine hydrochloride are largely the result of alpha-adrenergic agonist activity resulting from both direct stimulation of adrenergic receptors and release of neuronal norepinephrine. The principal adverse effect of phenylpropanolamine hydrochloride is dose-related hypertension and ventricular arrhythmia has been described. Phenylpropanolamine hydrochloride is widely used as a decongestant and it has been used as an anorectic agent for over 40 years. A report in 1939 described its effect as an hypertensive agent when administered parenterally.
- Full Text:
- Authors: Kanfer, Isadore , Haigh, John M , Dowse, Roslind
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6385 , http://hdl.handle.net/10962/d1006306
- Description: Phenylpropanolamine hydrochloride belongs to the sympathomimetic amine class of drugs and is structurally related to ephedrine hydrochloride. Its synthesis was first reported in 1910 and the first American patent was registered in 1939. The effects of phenylpropanolamine hydrochloride are largely the result of alpha-adrenergic agonist activity resulting from both direct stimulation of adrenergic receptors and release of neuronal norepinephrine. The principal adverse effect of phenylpropanolamine hydrochloride is dose-related hypertension and ventricular arrhythmia has been described. Phenylpropanolamine hydrochloride is widely used as a decongestant and it has been used as an anorectic agent for over 40 years. A report in 1939 described its effect as an hypertensive agent when administered parenterally.
- Full Text:
Possible dosage regimens for topical steroids assessed by vasoconstrictor assays using multiple applications
- Woodford, R, Haigh, John M, Barry, B W
- Authors: Woodford, R , Haigh, John M , Barry, B W
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6450 , http://hdl.handle.net/10962/d1006637
- Description: The bioavailabilities and activities of three amcinonide preparations and Betnovate cream were assessed using three multiple-dosage regimen vasoconstrictor assays in 10 volunteers. Applications were made once daily, twice daily and every alternate day with an initial three times daily loading dose applied on the first day only. Blanching responses first increased and then decreased due to tachyphylaxis. It is proposed that clinically the most advantageous dosage regimen is a once daily application with no loading dose.
- Full Text:
- Authors: Woodford, R , Haigh, John M , Barry, B W
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6450 , http://hdl.handle.net/10962/d1006637
- Description: The bioavailabilities and activities of three amcinonide preparations and Betnovate cream were assessed using three multiple-dosage regimen vasoconstrictor assays in 10 volunteers. Applications were made once daily, twice daily and every alternate day with an initial three times daily loading dose applied on the first day only. Blanching responses first increased and then decreased due to tachyphylaxis. It is proposed that clinically the most advantageous dosage regimen is a once daily application with no loading dose.
- Full Text:
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:
- 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: