Showing items 1 - 20 of 39

Your selections:

Application of the Minolta chromameter to the assessment of corticosteroid-induced skin blanching

Role of percutaneous penetration enhancers

  • Authors: Walker, Roderick B , Smith, Eric W
  • Date: 1996
  • Language: English
  • Type: text , Article
  • Identifier: vital:6446 , http://hdl.handle.net/10962/d1006633
  • Description: It is clear that scientists are now only beginning to comprehend the complexity of transdermal drug delivery. Elucidation of the biochemical composition and functioning of the intrinsic diffusional barrier of the stratum corneum has prompted investigation of chemical and physical means of enhancing the percutaneous penetration of poorly absorbed drugs. Chemical enhancers that aid absorption of co-administered moieties are currently believed to improve solubility within the stratum corneum or increase lipid fluidity of the intracellular bilayers. Alternatively,the use of ionto- or phonophoresis may facilitate the absorption of some drug molecules by physical alteration of the barrier. The role of penetration enhancer inclusion in topical formulations has been well documented and will undoubtedly, in the future, permit the delivery of broader classes of drugs through the stratum corneum.
  • Full Text:
  • Date Issued: 1996

Aspects of the transdermal permeation and analysis of betamethasone 17-valerate

  • Authors: Smith, Eric W
  • Date: 1988
  • Subjects: Transdermal medication Skin absorption Dermatologic agents
  • Language: English
  • Type: Thesis , Doctoral , PhD
  • Identifier: vital:3815 , http://hdl.handle.net/10962/d1004741
  • Description: The current world-wide interest in transdermal drug delivery makes the prospect of valid in vitro diffusion cell methodology highly attractive. A new laboratory diffusion cell has been designed and constructed based on theoretical principles and practical permeation reports surveyed in recent literature, and has been applied to the monitoring of betamethasone 17-valerate permeation. The cell performance has been validated with respect to hydrodynamic mixing efficiency and temperature of the receptor phase. The steady-state permeation of this corticosteroid has been monitored through various synthetic and animal membranes in order to select the most appropriate media for in vitro study. The permeation of betamethasone 17-valerate has been monitored from various types of commercial and extemporaneously prepared semisolid topical formulation (cream, lotion, ointment and scalp application), through silicone membrane, human and weanling pig stratum corneum, and full thickness hairless mouse skin, and these in vitro results have been compared to data from in vivo blanching assays, using the same formulations, in an attempt to correlate the findings. This experimental methodology has necessitated the development of ancillary analytical techniques. A column-switching high-performance liquid chromatographic method has been developed for the rapid on-line clean-up and analysis of betamethasone 17-valerate contained in the various topical formulations, which minimizes sample handling and extraction procedures. The method has been modified for the analysis of this corticosteroid in the isopropyl myristate receptor phase used in the in vitro permeation experiments, and scintillation counting of tritium-labelled water has been used to verify the integrity of the animal membranes. The comparison of in vitro permeation and in vivo blanching results indicate good correlation of the data in certain instances. The closest correlations have been observed when the human stratum corneum has been used in vitro and these results are compared to data from the occluded mode of the blanching assay. The results of the porcine and murine media have also correlated with the human in vivo data, whereas the silicone membrane appears applicable only in certain in vitro experiments. The results indicate that valid, comparative percutaneous absorption data may be obtained in vitro by using a well designed, validated diffusion cell system.
  • Full Text:
  • Date Issued: 1988

Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioeqivalence testing [authors' reply in Letters to the Editor]

  • Authors: Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
  • Date: 1998
  • Language: English
  • Type: text , Article
  • Identifier: vital:6423 , http://hdl.handle.net/10962/d1006558
  • Description: Reply to: Letter to the Editor by Singh GJ; Fleischer N; Lesko L; Williams R - relating to original article in Pharmaceutical Research (USA), Mar 1997, vol. 14, pp. 303-308.
  • Full Text: false
  • Date Issued: 1998

A stability-indicating HPLC assay with on-line clean-up for betamethasone 17-valerate in topical dosage forms

  • Authors: Smith, Eric W , Haigh, John M , Kanfer, Isadore
  • Date: 1985
  • Language: English
  • Type: Article
  • Identifier: vital:6421 , http://hdl.handle.net/10962/d1006556
  • Description: A stability-indicating high-performance liquid chromatographic method with on-line clean-up has been developed for the analysis of betamethasone 17-valerate in topical dosage forms. A short pre-column containing 10 μm octadecylsilane mounted into the sample loop position of an injection valve was used as the primary clean-up step. The utilization of a diode-array UV detector allowed the quantitative analysis of betamethasone 17-valerate together with its degradation product, betamethasone 21-valerate, as well as the qualitative analysis of these compounds, relevant internal standards and the preservatives chlorocresol and methyl hydroxybenzoate contained in the cream and lotion formulations, respectively. Typically, cream and lotion dosage forms were dissolved in acetonitrile and ointments in tetrahydrofuran, internal standards added and aliquots injected onto the analytical system. Dosage form excipients were retained on the loop column and back-flushed to waste with the aid of a second solvent pump while components of interest were allowed to transfer to the analytical column for quantitative analysis. The method is accurate, precise and stability indicating and permits the rapid on-line analysis of betamethasone 17-valerate from complex topical formulation matrices without prior extractions.
  • Full Text:
  • Date Issued: 1985

Precision of tristimulus chromameter results from corticosteroid-induced skin blanching

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1998
  • Language: English
  • Type: Conference paper
  • Identifier: vital:6342 , http://hdl.handle.net/10962/d1006609
  • Description: The human skin blanching (vasoconstriction) assay has been in use for 3 decades as a tool for the assessment of the release of corticosteroids from topical dosage forms. Application of corticosteroids produces a whitening (blanching) of the skin, the intensity of which is directly related to the clinical efficacyof the formulation. Assessment of the intensity of the induced blanching has classically been, and continues to be, pe1fonned by visual grading, a method which has been criticised because of the subjectivenature of the assessment Recently there has been considerablediscussion in the literature regarding the use of the chromameter as an objective instrumental method of monitoring corticosteroid induced skin blanching for bioequivalence assessment purposes. The FDA has released a Guidance document recommending the use of the chromameter for this purpose. The chromameter measures colour in teims of three indices: the L-scale (light-dark), the a-scale (red-green) and the b-scale (yellow-blue).Any colour can be expressedabsolutelyin terms of these three values.The Guidance protocol suggests the use of only the a-scale values in quantifying the blanching response after correction of the data which includes subtraction of baseline and unmedicated site values. One of the unresolved issues in the FDA Guidance document is this method of data manipulation suggested since the instrument should be capable of assigning an absolute colour value to each site during the vasoconstriction period. The purpose of this study was to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriatenessof these suggested procedures.
  • Full Text:
  • Date Issued: 1998

Quantification of corticosteroid-induced skin vasoconstriction: visual ranking, chromameter measurement or digital image analysis

  • 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

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

  • 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

Ranking of topical corticosteroids: principles and results

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1993
  • Language: English
  • Type: text , Article
  • Identifier: vital:6434 , http://hdl.handle.net/10962/d1006607
  • Description: The increasing synthesis and use of topical corticosteroid products over the past 30 years has necessitated the development of suitable methods for evaluating the efficacy and potency of new drug entities. Several in vivo models have been developed in this regard using laboratory animals and human subjects. Generally, these tests measure the difference in the non-immunological inflammatory response to an exogenous inflammatory mediator in the presence and absence of the corticosteroid under test. There are also immunologically based assays and several tests which assess the anti proliferative effects of the drug. Several comparative disease model evaluations have also been developed using human subjects. Most of these assays are non-ideal from one point of view or another: most are invasive methods which require some form of trauma to be induced in the skin and therefore problematic to perform and monitor.
  • Full Text:
  • Date Issued: 1993

The human skin-blanching assay for comparing topical corticosteroid availability

  • 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. II. Temperature, agitation and membrane effects on betamethasone 17-valerate permeation

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1992
  • Language: English
  • Type: text , Article
  • Identifier: vital:6422 , http://hdl.handle.net/10962/d1006557
  • Description: An in vitro permeation cell has been designed and validated for use in monitoring the transmembrane permeation of betamethasone 17-valerate. The design utilizes common laboratory equipment and incorporates as many beneficial features as possible from other designs. The importance of fully validating the hydrodynamic performance of the cell prior to experimentation is stressed. The cell was validated by monitoring the diffusion of betamethasone 17-valerate in isopropyl myristate solution into purified isopropyl myristate receptor phase at different temperatures, different agitation rates and through different synthetic and biological membranes. The results of the hydrodynamic validation agree with data from other researchers and show that the permeation cell is adequately sensitive to these experimental parameters. The results of the membrane evaluation allow appropriate selection of the barrier material for representative transdermal experiments to be conducted. While human and porcine stratum corneum/epidermis are similar in diffusive properties, hairless mouse skin appears to be the most convenient animal membrane for these studies. Although silicone and cellulose membranes appear to be useful in this application, porous filter membranes and egg-shell membranes are insufficiently discriminatory to betamethasone 17-valerate diffusion to provide useful in vitro permeation data.
  • Full Text: false
  • Date Issued: 1992

The human skin-blanching assay as an indicator of topical corticosteroid bioavailability and potency: an update

  • Authors: Smith, Eric W , Meyer, Eric , Haigh, John M , Maibach, Harold I
  • Date: 1989
  • Language: English
  • Type: Book chapter
  • Identifier: vital:6440 , http://hdl.handle.net/10962/d1006627 , ISBN 0824780361
  • Description: The human skin-blanching (or vasoconstrictor) assay has evolved from initial observations that corticosteroids induce a pallor or whitening of the skin to which they are applied. McKenzie and Stoughton (1962) are generally recognized as having developed the first scientific bioassay for comparing corticosteroid potency. The extensive use of this bioassay to compare drug release from topical delivery systems has demonstrated numerous instances in which the topical bioavailability may vary greatly, dependent on the character of the delivery vehicle. It has become evident that simply incorporating an intrinsically potent drug into a formulation does not necessarily produce a clinically efficacious product.
  • Full Text:
  • Date Issued: 1989

Blanching activities of betamethasone 17-valerate formulations: effect of the dosage form on topical drug availability

  • Authors: Smith, Eric W , Meyer, Eric , Haigh, John M
  • Date: 1990
  • Language: English
  • Type: Article
  • Identifier: vital:6432 , http://hdl.handle.net/10962/d1006602
  • Description: The blanching activities of Betnovate© cream, lotion, ointment and scalp application (each containing 0.1 % betamethasone (as the 17-valerate)) were determined using healthy human subjects over a 32 h period in both the occludedand unoccluded modes. Considering that allfour formulation types contained the same label concentration of corticosteroid,it may bepresumed that theformulations would show similar topical drug availability: this was, however, not found to be the case. The scalp application demonstrated the highest topical availability in both the occluded and unoccluded modes. The lotion formulation showed the greatest increase in topical availability on occlusion and the ointment formulation was the least sensitive to the effects of occlusion. These differences, due solely to the effects of the vehicle, may have important clinical implications.
  • Full Text:
  • Date Issued: 1990

In vitro systems for the assessment of drug release from topical formulations and trans-membrane permeation

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1989
  • Language: English
  • Type: Book chapter
  • Identifier: vital:6441 , http://hdl.handle.net/10962/d1006628
  • Description: Numerous experimental methods have been developed to investigate drug release from vehicles and the percutaneous absorption of topically applied chemicals. The objective of this research is often to find correlation between laboratory results and the transdermal absorption experienced by living subjects so that in vivo experimentation may be curtailed. In many instances, the diverse experimental techniques tend to obscure absorption-controlling factors and complicate inter study comparisons, rather than clarify the complex transdermal absorption process. Moreover, lack of agreement between results may occasionally be ascribed to shortcomings in the in vitro methodology employed. The benefits of using an in vitro cell system for the preliminary testing of drug permeation in the laboratory are obvious. The environmental and diffusion variables may be controlled in an attempt to elucidate specific factors affecting the kinetic processes and drug bioavailability. Investigations are complex because of the multiple, interrelated events underlying the processes of drug partitioning from the applied vehicle and diffusion through the portals of the stratum corneum to the myriad of metabolic, binding, and clearance activities in the lower epidermal and dermal strata.
  • Full Text:
  • Date Issued: 1989

In vitro release of propranolol hydrochloride from topical vehicles

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1994
  • Language: English
  • Type: text , Article
  • Identifier: vital:6435 , http://hdl.handle.net/10962/d1006612
  • Description: Transdermal drug delivery is becoming increasingly important and for this reason it is clear that academia must ensure that current graduates are knowledgeable in all facets of topical drug administration. An in vitro diffusion cell experiment was designed to demonstrate the rate of release of propranolol hydrochloride (PHC) from three different topical vehicles: (i) an oil-in-water cream; (ii) a gel; and (iii) anointment. This experiment was performed by final-year students enroled in an undergraduate course on percutaneous absorption. In vitro release of PHC from the three bases to an aqueous receptor phase through silicone membrane was monitored spectrophotometrically at a wavelength of 290 nm. By monitoring and attempting to explain the numerous possible reasons for the different rates of drug release from the three vehicles, it was hoped that the students would gain a better understanding of the complexities of transdermal drug administration. Overall, the experiment would appear to be a good model for student investigation into factors affecting the release of drugs from topical formulations.
  • Full Text:
  • Date Issued: 1994

Assessing penetration enhances for topical corticosteroids

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1995
  • Language: English
  • Type: Book chapter
  • Identifier: vital:6442 , http://hdl.handle.net/10962/d1006629
  • Description: From introduction: Topical corticosteroids have been used for a wide range of dermatological conditions for the last 4 decades. For many years the topical delivery system was a relatively simple cream or ointment base, with little thought given to improving the formulation as far as drug delivery was concerned. The main emphasis in the initial stages of development was on the alteration of the corticosteroid molecule, in an attempt to produce moieties with a higher intrinsic topical effect with lower mineralocorticoid side effects. Once this avenue of research was exhausted, attention was placed on the lipophilicity of the molecule with the production of various types of esters in an attempt to produce molecules which would pass through the stratum corneum (SC) with reasonable ease. In recent years the nature of the semisolid drug delivery base has received considerable attention.2-5The nature of the vehicle has a profound effect on the rate of release of the topical corticosteroid from the formulation and its passage through the SC. One of the most important aspects of the formulation of the base is the inclusion of substances which aid this trads-SC diffusion, the so-called penetration enhancers.6The modes of action of the various different types of penetration enhancers are reviewed elsewhere in this book. The best method for the assessment of the release of corticosteroids from topical formulations is obviously the clinical tri~. Clinical trials, however, are laborious, costly, and difficult to mount. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid formulations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between formulations. Alternatively, a number of in vitro models exist for this type of assessment, but it is often problematic to obtain correlation with the in vivo situation.
  • Full Text:
  • Date Issued: 1995

Accuracy and reproducibility of the multiple-reading skin blanching assay

  • Authors: Smith, Eric W , Meyer, Eric , Haigh, John M
  • Date: 1992
  • Language: English
  • Type: Book chapter
  • Identifier: vital:6439 , http://hdl.handle.net/10962/d1006625
  • Full Text:
  • Date Issued: 1992

In vivo/in vitro assessments of topical hydrocortisone availability: correlation between blanching assay and laboratory cell experiments

  • Authors: Smith, Eric W , Haigh, John M
  • Date: 1995
  • Language: English
  • Type: Book chapter
  • Identifier: vital:6438 , http://hdl.handle.net/10962/d1006624
  • Description: From introduction: Topical corticosteroids are still the most widely used drugs in the treatment of dermatological conditions. Early corticosteroid dosage forms consisted of simple creams or ointments where more emphasis was placed on the potency of the drug molecule than on the intrinsic delivery potential of the vehicle. More recently, the effect that the composition of the semisolid base has on the extent of drug delivery has been researched to a much greater extent. These advances in the science of dosage form design have necessitated the refinement of precise and accurate methods for testing the drug delivery efficacies of the developed products. Obviously, the best method for the assessment of the effectiveness of corticosteroid formulations is in a therapeutic situation. Clinical trials, however, are fraught with methodological problems that make duplication of a trial impossible. Alternatively, a number of pharmacological models4 exist for this type of assessment, but it is often problematic to obtain correlation with the true dermatological conditions. The human skin blanching assay is one of the most reliable and reproducible of the ill vivo methods available for the assessment of topical corticosteroid formulations. The skin whitening (blanching or vasoconstriction) side-effect that follows corticosteroid application was first utilized in 1962 as a measure of the percutaneous absorption of corticosteroids from topical formulations. Optimization of this initial procedure7.s has produced a reliable and precise bioassay methodology for the assessment of the efficacy of topical corticosteroid formulations. One criticism of this assay has been the subjective nature of the observation procedure. Although these points have repeatedly been addressed in the literature, it has been suggested that it would be beneficial to have some ill vitro penetration data to supplement ill vivo observations, as this would strengthen the assessment of the topical equivalence of similar delivery formulations. With this objective in mind, a comparison of hydrocortisone release from two proprietary cream formulations was compared by in vivo and ill vitro techniques to determine if any correlation could be established between the methodologies.
  • Full Text:
  • Date Issued: 1995

Analysis of chromameter results obtained from corticosteroid-induced skin blanching. I. Manipulation of data

  • Authors: Smith, Eric W , Haigh, John M , Walker, Roderick B
  • Date: 1998
  • Language: English
  • Type: text , Article
  • Identifier: vital:6424 , http://hdl.handle.net/10962/d1006559
  • Description: Purpose. One of the unresolved issues in the FDA Guidance document for topical corticosteroid bioequivalence testing is the method of manipulation suggested for the chromameter data. The purpose of this study was to manipulate the instrumental data from a typical blanching study in a number of ways to investigate the appropriateness of these procedures for comparison with the subjective visually-assessed results. Methods. The human skin blanching assay methodology routinely practiced in our laboratories was utilised and the vasoconstriction produced by two corticosteroid formulations of different potency was assessed visually and instrumentally by use of a Minolta chromameter. The instrumental data were corrected for zero-time and unmedicated site readings. In addition, Euclidean distances were calculated using all data generated by the instrument. Results. Individually the a-, b- and L-scale chromameter values are imprecise and there is negligible vasoconstriction response recorded for the moderately potent formulation. Arithmetical manipulation of the data as suggested by the FDA does not appear to improve the quality of the data in any way. Euclidean distance analysis more closely resembles the visual data and appears to have better precision. Conclusions. It is clear that mathematical correction of chromameter data is unnecessary, especially since the instrumental data are extremely imprecise. Furthermore, the assessment of each individual chromameter index does not adequately characterise the blanching response profile. It is therefore suggested that Euclidean distance may be a better measure on which to base an analysis of bioequivalence than the truncated data set methodology currently suggested by the FDA.
  • Full Text: false
  • Date Issued: 1998

Comparison of visual CR-200 and CR-300 chromameter data obtained from the corticosteroid-induced skin-blanching assay

  • 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
  • Disclaimer
  • Privacy
  • Copyright
  • Contact