Quantification of corticosteroid-induced skin vasoconstriction: visual ranking, chromameter measurement or digital image analysis
- Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 2002
- Language: English
- Type: text , Article
- Identifier: vital:6427 , http://hdl.handle.net/10962/d1006564
- Description: Topical corticosteroid formulations have been evaluated by visual grading protocols for many years. Toward a more objective methodology, several instrumental methods have been evaluated for applicability in quantifying the vasoconstriction side-effect that follows corticosteroid application to the skin. Although the chromameter has been adopted by regulatory bodies throughout the world as the current standard for topical bioequivalence determinations, there is considerable criticism of this instrument from several quarters. A preliminary comparison reported here indicates that digital image analysis provides statistically significant results that are similar to those obtained by visual assessment techniques, and shows considerably greater precision than that obtained by the chromameter. Continued evaluation of objective assessment techniques, such as digital imaging, and continued modernisation of regulatory bioequivalence requirements will assist in protecting patients and optimising clinical results.
- Full Text:
- Date Issued: 2002
- Authors: Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 2002
- Language: English
- Type: text , Article
- Identifier: vital:6427 , http://hdl.handle.net/10962/d1006564
- Description: Topical corticosteroid formulations have been evaluated by visual grading protocols for many years. Toward a more objective methodology, several instrumental methods have been evaluated for applicability in quantifying the vasoconstriction side-effect that follows corticosteroid application to the skin. Although the chromameter has been adopted by regulatory bodies throughout the world as the current standard for topical bioequivalence determinations, there is considerable criticism of this instrument from several quarters. A preliminary comparison reported here indicates that digital image analysis provides statistically significant results that are similar to those obtained by visual assessment techniques, and shows considerably greater precision than that obtained by the chromameter. Continued evaluation of objective assessment techniques, such as digital imaging, and continued modernisation of regulatory bioequivalence requirements will assist in protecting patients and optimising clinical results.
- Full Text:
- Date Issued: 2002
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:
- Date Issued: 1991
- 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:
- Date Issued: 1991
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:
- Date Issued: 1989
- 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:
- Date Issued: 1989
Comparison of visual CR-200 and CR-300 chromameter data obtained from the corticosteroid-induced skin-blanching assay
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper , text
- Identifier: vital:6344 , http://hdl.handle.net/10962/d1006611
- Description: In a recent Guidance document the American FDA recommended the use of a chromameterrather thanthe human eye for the assessment of the pharmacodynamic blanching response produced after topical application of corticosteroids. The purpose of this study was to investigate the appropriateness of the human eye and two types of chromameter for the estimation of skin blanching.
- Full Text:
- Date Issued: 1998
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper , text
- Identifier: vital:6344 , http://hdl.handle.net/10962/d1006611
- Description: In a recent Guidance document the American FDA recommended the use of a chromameterrather thanthe human eye for the assessment of the pharmacodynamic blanching response produced after topical application of corticosteroids. The purpose of this study was to investigate the appropriateness of the human eye and two types of chromameter for the estimation of skin blanching.
- Full Text:
- Date Issued: 1998
Analysis of chromameter results obtained from corticosteroid-induced skin blanching assay: comparison of visual and chromameter data
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6426 , http://hdl.handle.net/10962/d1006562
- Description: In a Guidance document, the American FDA recommends the use of a Minolta chromameter rather than the human eye for the quantitative assessment of the pharmacodynamic blanching response produced by topical application of corticosteroids. The purpose of this study was to compare the appropriateness of the human eye and two models of chromameter for the estimation of skin blanching, in terms of the quality of the data generated by each method. The corticosteroid-induced skin blanching from four different betamethasone 17-valerate cream formulations was compared in a typical human skin blanching trial. The optimized assay methodology routinely practised in our laboratories was utilized. The blanching responses were assessed visually by three trained, independent observers and recorded by two chromameters (Minolta model CR-200 and model CR-300). The topical availability of the four creams was determined using visual scoring and chromameter measurements. All data were manipulated in such a manner as to produce a blanching response versus time profile from which AUBC analysis could be performed. Good correlation was observed between the visual assessments made by three independent observers. In contrast, moderate correlation was determined between visual, CR-200 and CR-300 measurements. Surprisingly, no direct linear relationship between the AUBCs produced by the two chromameters was observed indicating that the quality of the data obtained from the two instruments may not be equal. This investigation also indicated that the use of the chromameter is not completely objective. Visual scoring and chromameter measurement produce data sets that differ in quality. Each procedure needs to be validated and investigators have to be trained for both visual assessment and the operation of the chromameter, particularly with regard to the manipulation of the measuring head of the instrument.
- Full Text:
- Date Issued: 1999
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6426 , http://hdl.handle.net/10962/d1006562
- Description: In a Guidance document, the American FDA recommends the use of a Minolta chromameter rather than the human eye for the quantitative assessment of the pharmacodynamic blanching response produced by topical application of corticosteroids. The purpose of this study was to compare the appropriateness of the human eye and two models of chromameter for the estimation of skin blanching, in terms of the quality of the data generated by each method. The corticosteroid-induced skin blanching from four different betamethasone 17-valerate cream formulations was compared in a typical human skin blanching trial. The optimized assay methodology routinely practised in our laboratories was utilized. The blanching responses were assessed visually by three trained, independent observers and recorded by two chromameters (Minolta model CR-200 and model CR-300). The topical availability of the four creams was determined using visual scoring and chromameter measurements. All data were manipulated in such a manner as to produce a blanching response versus time profile from which AUBC analysis could be performed. Good correlation was observed between the visual assessments made by three independent observers. In contrast, moderate correlation was determined between visual, CR-200 and CR-300 measurements. Surprisingly, no direct linear relationship between the AUBCs produced by the two chromameters was observed indicating that the quality of the data obtained from the two instruments may not be equal. This investigation also indicated that the use of the chromameter is not completely objective. Visual scoring and chromameter measurement produce data sets that differ in quality. Each procedure needs to be validated and investigators have to be trained for both visual assessment and the operation of the chromameter, particularly with regard to the manipulation of the measuring head of the instrument.
- Full Text:
- Date Issued: 1999
Effect of concentration and degree of saturation of topical fluocinonide formulations on in vitro membrane transport and in vivo availability on human skin
- Schwarb, Fabian P, Imanidis, Georgios, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Imanidis, Georgios , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6425 , http://hdl.handle.net/10962/d1006560
- Description: Purpose. The thermodynamic acitvity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. Methods. Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. Results. Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. Conclusions. From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.
- Full Text: false
- Date Issued: 1999
- Authors: Schwarb, Fabian P , Imanidis, Georgios , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1999
- Language: English
- Type: text , Article
- Identifier: vital:6425 , http://hdl.handle.net/10962/d1006560
- Description: Purpose. The thermodynamic acitvity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. Methods. Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. Results. Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. Conclusions. From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.
- Full Text: false
- Date Issued: 1999
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
Chromametry: measuring precision of diurnal and local variation of human forearm skin colour
- Schwarb, Fabian P, Smith, Eric W, Haigh, John M, Surber, Christian
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6343 , http://hdl.handle.net/10962/d1006610
- Description: Chromameters are compact portable instruments used for the assessment of surface colour based on the tristimulus analysis of a reflected xenon light pulse, and have been used for the quantification of erythema in the study of irritant dermatitis, and corticosteroid-induced skin blanching in the vasoconstriction assay. The variability and the reproducibility of chromameter results were investigated since it is known that the location and application force of the measuring head on the skin and the orthostatic maneuver of the arms influence the colour measurement. Furthermore the diurnal variation and the homogeneity of forearm skin colour were investigated.
- Full Text:
- Date Issued: 1998
- Authors: Schwarb, Fabian P , Smith, Eric W , Haigh, John M , Surber, Christian
- Date: 1998
- Language: English
- Type: Conference paper
- Identifier: vital:6343 , http://hdl.handle.net/10962/d1006610
- Description: Chromameters are compact portable instruments used for the assessment of surface colour based on the tristimulus analysis of a reflected xenon light pulse, and have been used for the quantification of erythema in the study of irritant dermatitis, and corticosteroid-induced skin blanching in the vasoconstriction assay. The variability and the reproducibility of chromameter results were investigated since it is known that the location and application force of the measuring head on the skin and the orthostatic maneuver of the arms influence the colour measurement. Furthermore the diurnal variation and the homogeneity of forearm skin colour were investigated.
- Full Text:
- Date Issued: 1998
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
The structure of aliphatic amine adducts of uranyl acetylacetonate. IV. Dioxobis(2,4-pentanedionato) mono(2-aminopentan-4-one)uranium(VI)
- Rodgers, A L, Nassimbeni, L R, Pauptit, R A, Orpen, G, Haigh, John M
- Authors: Rodgers, A L , Nassimbeni, L R , Pauptit, R A , Orpen, G , Haigh, John M
- Date: 1977
- Language: English
- Type: text , Article
- Identifier: vital:6420 , http://hdl.handle.net/10962/d1006555
- Description: Introduction: We have shown in three earlier determinations of aliphatic amine adducts of U02(AA)2 (part I: Haigh, Nassimbeni, Pauptit, Rodgers & Sheldrick, 1976; part II: Nassimbeni, Orpen, Pauptit, Rodgers & Haigh, 1977; part III: Rodgers, Nassimbeni & Haigh, 1977) that the conformation of the adduct is dependent on its ability to form hydrogen bonds. The present compound has two H atoms available for hydrogen bonding and may be regarded as the parent of the series.
- Full Text:
- Date Issued: 1977
- Authors: Rodgers, A L , Nassimbeni, L R , Pauptit, R A , Orpen, G , Haigh, John M
- Date: 1977
- Language: English
- Type: text , Article
- Identifier: vital:6420 , http://hdl.handle.net/10962/d1006555
- Description: Introduction: We have shown in three earlier determinations of aliphatic amine adducts of U02(AA)2 (part I: Haigh, Nassimbeni, Pauptit, Rodgers & Sheldrick, 1976; part II: Nassimbeni, Orpen, Pauptit, Rodgers & Haigh, 1977; part III: Rodgers, Nassimbeni & Haigh, 1977) that the conformation of the adduct is dependent on its ability to form hydrogen bonds. The present compound has two H atoms available for hydrogen bonding and may be regarded as the parent of the series.
- Full Text:
- Date Issued: 1977
Foam drug delivery in dermatology: beyond the scalp
- Purdon, Carryn H, Haigh, John M, Surber, Christian, Smith, Eric W
- Authors: Purdon, Carryn H , Haigh, John M , Surber, Christian , Smith, Eric W
- Date: 2003
- Subjects: Adis International Limited , Drug delivery systems , Skin disorders
- Language: English
- Type: text , Article
- Identifier: vital:6418 , http://hdl.handle.net/10962/d1006541
- Description: Consumers of topical formulations apply a wide spectrum of preparations, both cosmetic and dermatological, to their healthy or diseased skin. These formulations range in physicochemical nature from solid through semisolid to liquid. Pharmaceutical foams are pressurized dosage forms containing one or more active ingredients that, upon valve actuation, emit a fine dispersion of liquid and/or solid materials in a gaseous medium. Foam formulations are generally easier to apply, are less dense, and spread more easily than other topical dosage forms. Foams may be formulated in various ways to provide emollient or drying functions to the skin, depending on the formulation constituents. Therefore, this delivery technology should be a useful addition to the spectrum of formulations available for topical use; however, as yet, only a few are commercially available. Probably the most convincing argument for the use of foams is ease of use by the patient, and consumer acceptance. Most foam dosage forms used in dermatology to date have incorporated corticosteroids, although some products have also been used to deliver antiseptics, antifungal agents, anti-inflammatory agents, local anesthetic agents, skin emollients, and protectants. Although there is no clinical evidence that foam formulations are currently superior to other conventional delivery vehicles, these formulations have a clear application advantage and with continued developments in the science of supersaturation technology, it seems certain that foam delivery systems will retain their place in the dermatological and cosmetic armamentarium.
- Full Text:
- Date Issued: 2003
- Authors: Purdon, Carryn H , Haigh, John M , Surber, Christian , Smith, Eric W
- Date: 2003
- Subjects: Adis International Limited , Drug delivery systems , Skin disorders
- Language: English
- Type: text , Article
- Identifier: vital:6418 , http://hdl.handle.net/10962/d1006541
- Description: Consumers of topical formulations apply a wide spectrum of preparations, both cosmetic and dermatological, to their healthy or diseased skin. These formulations range in physicochemical nature from solid through semisolid to liquid. Pharmaceutical foams are pressurized dosage forms containing one or more active ingredients that, upon valve actuation, emit a fine dispersion of liquid and/or solid materials in a gaseous medium. Foam formulations are generally easier to apply, are less dense, and spread more easily than other topical dosage forms. Foams may be formulated in various ways to provide emollient or drying functions to the skin, depending on the formulation constituents. Therefore, this delivery technology should be a useful addition to the spectrum of formulations available for topical use; however, as yet, only a few are commercially available. Probably the most convincing argument for the use of foams is ease of use by the patient, and consumer acceptance. Most foam dosage forms used in dermatology to date have incorporated corticosteroids, although some products have also been used to deliver antiseptics, antifungal agents, anti-inflammatory agents, local anesthetic agents, skin emollients, and protectants. Although there is no clinical evidence that foam formulations are currently superior to other conventional delivery vehicles, these formulations have a clear application advantage and with continued developments in the science of supersaturation technology, it seems certain that foam delivery systems will retain their place in the dermatological and cosmetic armamentarium.
- Full Text:
- Date Issued: 2003
The use of supersaturated solutions for the percutaneous delivery of rooperol tetra-acetate
- Pefile, S C, Haigh, John M, Smith, Eric W
- Authors: Pefile, S C , Haigh, John M , Smith, Eric W
- Date: 1998
- Language: English
- Type: Conference paper , text
- Identifier: vital:6340 , http://hdl.handle.net/10962/d1006537
- Description: A major problem encountered in the transdermal delivery of drugs is the effectiveness of the barrier system imposed by the stratum corneum.To overcome tbe resistance of the skin to the ingress of exogenous chemicals, numerous innovative techniques requiring complex delivery systems have been studied. Many of these systems attempt to alter the barrier potential by the use of enhancer technology. Supersaturation, on the other hand, is a simple and economical technique which is not intended to modify the physical structure or the chemical composition of the stratum corneum, yet may effectively deliver a markedly greater mass of drug to the skin than that achieved by the use of conventional, saturated solutions. Supersaturated systems make use of the elevated thermodynamic activity of the permeant in the delivery vehicle, which results in higher flux rates across the contacting membrane by increasing the concentration gradient. The present study investigated the potential for using supersaturation techniques to transdermally deliver rooperol tetra-acetate (RTA), a lipophilic, cytotoxic agent with potential for use in the treatment of solar keratosis. The diffusion characteristics of the drug from a 60% propylene glycol/water supersaturated solution across silicone membrane and full thickness rat skin were studied using Franz diffusion cells. A comparison was made of the drug diffusion rates from a saturated system and from supersaturated systems prepared with and without an antinucleating agent.
- Full Text:
- Date Issued: 1998
- Authors: Pefile, S C , Haigh, John M , Smith, Eric W
- Date: 1998
- Language: English
- Type: Conference paper , text
- Identifier: vital:6340 , http://hdl.handle.net/10962/d1006537
- Description: A major problem encountered in the transdermal delivery of drugs is the effectiveness of the barrier system imposed by the stratum corneum.To overcome tbe resistance of the skin to the ingress of exogenous chemicals, numerous innovative techniques requiring complex delivery systems have been studied. Many of these systems attempt to alter the barrier potential by the use of enhancer technology. Supersaturation, on the other hand, is a simple and economical technique which is not intended to modify the physical structure or the chemical composition of the stratum corneum, yet may effectively deliver a markedly greater mass of drug to the skin than that achieved by the use of conventional, saturated solutions. Supersaturated systems make use of the elevated thermodynamic activity of the permeant in the delivery vehicle, which results in higher flux rates across the contacting membrane by increasing the concentration gradient. The present study investigated the potential for using supersaturation techniques to transdermally deliver rooperol tetra-acetate (RTA), a lipophilic, cytotoxic agent with potential for use in the treatment of solar keratosis. The diffusion characteristics of the drug from a 60% propylene glycol/water supersaturated solution across silicone membrane and full thickness rat skin were studied using Franz diffusion cells. A comparison was made of the drug diffusion rates from a saturated system and from supersaturated systems prepared with and without an antinucleating agent.
- Full Text:
- Date Issued: 1998
The crystal and molecular structure of the bis(4-N, N1-dimethylaminopyridine) solvate of disalicylicacidatobis(nitrotodioxouranium)(VI)
- Nassimbeni, L R, Rodgers, Allen L, Haigh, John M
- Authors: Nassimbeni, L R , Rodgers, Allen L , Haigh, John M
- Date: 1976
- Language: English
- Type: text , Article
- Identifier: vital:6415 , http://hdl.handle.net/10962/d1006526
- Description: The structure of the title compound [(C7H4NO8U)(C7H11N2)]2 has been determined by Patterson and Fourier methods from single crystal X-ray diffraction data collected on a four-circle diffractometer. Full-matrix least-squares refinement yielded a final conventional R of 0.041 for 2189 reflections. The complex crystallizes in the space group P with a = 11.004(5), b = 9.981(5), c = 9.928(5) Å, α = 119.6(3), β = 107.7(3), γ = 81.9(3)°, Dm = 2.17, Dc = 2.173g cm−3. The structure is dimeric. The uranium atoms are eight-coordinate and are bridged via centrosymmetrically related carboxylic oxygen atoms. The nitrate group is bidentate and the average U---O (ligand) distance is 2.463 Å. Hydrogen bonding of the type N---HO links two dimethyl-aminopyridine molecules to the dimer.
- Full Text:
- Date Issued: 1976
- Authors: Nassimbeni, L R , Rodgers, Allen L , Haigh, John M
- Date: 1976
- Language: English
- Type: text , Article
- Identifier: vital:6415 , http://hdl.handle.net/10962/d1006526
- Description: The structure of the title compound [(C7H4NO8U)(C7H11N2)]2 has been determined by Patterson and Fourier methods from single crystal X-ray diffraction data collected on a four-circle diffractometer. Full-matrix least-squares refinement yielded a final conventional R of 0.041 for 2189 reflections. The complex crystallizes in the space group P with a = 11.004(5), b = 9.981(5), c = 9.928(5) Å, α = 119.6(3), β = 107.7(3), γ = 81.9(3)°, Dm = 2.17, Dc = 2.173g cm−3. The structure is dimeric. The uranium atoms are eight-coordinate and are bridged via centrosymmetrically related carboxylic oxygen atoms. The nitrate group is bidentate and the average U---O (ligand) distance is 2.463 Å. Hydrogen bonding of the type N---HO links two dimethyl-aminopyridine molecules to the dimer.
- Full Text:
- Date Issued: 1976
The structure of aliphatic amine adducts of uranyl acetylacetonate. II. Dioxobis(2,4-pentanedionato)mono (2-N,N-dimethylaminopentan-4-one)uranium(VI)
- Nassimbeni, L R, Orpen, G, Pauptit, R A, Rodgers, Allen L, Haigh, John M
- Authors: Nassimbeni, L R , Orpen, G , Pauptit, R A , Rodgers, Allen L , Haigh, John M
- Date: 1977
- Language: English
- Type: text , Article
- Identifier: vital:6416 , http://hdl.handle.net/10962/d1006533
- Description: Introduction: In a previous analysis of a compound of this type, we have established that the adduct molecule is bonded through O and that the geometry about U is pentagonal bipyramidal (Haigh, Nassimbeni, Pauptit, Rodgers & Sheldrick, 1976). We have carried out the present analysis to study the conformational effects on the ligand brought about by substitution at N.
- Full Text:
- Date Issued: 1977
- Authors: Nassimbeni, L R , Orpen, G , Pauptit, R A , Rodgers, Allen L , Haigh, John M
- Date: 1977
- Language: English
- Type: text , Article
- Identifier: vital:6416 , http://hdl.handle.net/10962/d1006533
- Description: Introduction: In a previous analysis of a compound of this type, we have established that the adduct molecule is bonded through O and that the geometry about U is pentagonal bipyramidal (Haigh, Nassimbeni, Pauptit, Rodgers & Sheldrick, 1976). We have carried out the present analysis to study the conformational effects on the ligand brought about by substitution at N.
- Full Text:
- Date Issued: 1977
Comparative bioavailability of some locally manufactured betamethasone valerate containing preparations
- Meyer, Eric, Haigh, John M, Kanfer, Isadore
- Authors: Meyer, Eric , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6399 , http://hdl.handle.net/10962/d1006326
- Description: The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application.
- Full Text:
- Date Issued: 1983
- Authors: Meyer, Eric , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6399 , http://hdl.handle.net/10962/d1006326
- Description: The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application.
- Full Text:
- Date Issued: 1983
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
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
Sensitivity of different areas of the flexor aspect of the human forearm to corticosteroid-induced skin blanching
- Meyer, Eric, Smith, Eric W, Haigh, John M
- Authors: Meyer, Eric , Smith, Eric W , Haigh, John M
- Date: 1992
- Language: English
- Type: Article
- Identifier: vital:6394 , http://hdl.handle.net/10962/d1006317
- Description: The intensity of corticosteroid-induced blanching has been found to vary at different areas of the flexor aspect of the human forearm. A retrospective analysis of 38,880 observations of skin blanching in 56 volunteers was conducted to assess the sensitivity of forearm skin to betamethasone 17-valerate. The mid-forearm appears to be more sensitive to the blanching response than do the areas close to the wrist or elbow. These results indicate that each preparation under evaluation should be applied to several sites along the forearm when using the human skin blanching assay in order to obtain an accurate comparative assessment of corticosteroid release from topical delivery vehicles.
- Full Text: false
- Date Issued: 1992
- Authors: Meyer, Eric , Smith, Eric W , Haigh, John M
- Date: 1992
- Language: English
- Type: Article
- Identifier: vital:6394 , http://hdl.handle.net/10962/d1006317
- Description: The intensity of corticosteroid-induced blanching has been found to vary at different areas of the flexor aspect of the human forearm. A retrospective analysis of 38,880 observations of skin blanching in 56 volunteers was conducted to assess the sensitivity of forearm skin to betamethasone 17-valerate. The mid-forearm appears to be more sensitive to the blanching response than do the areas close to the wrist or elbow. These results indicate that each preparation under evaluation should be applied to several sites along the forearm when using the human skin blanching assay in order to obtain an accurate comparative assessment of corticosteroid release from topical delivery vehicles.
- Full Text: false
- Date Issued: 1992
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
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