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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

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

Analysis of chromameter results obtained from corticosteroid-induced skin blanching assay: comparison of visual and chromameter data

  • 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

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

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

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

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.
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  • Date Issued: 1995

Bioequivalence testing of topical dermatological formulations, the gap between science and legislation

  • 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

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.
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  • Date Issued: 1990

Chromametry: measuring precision of diurnal and local variation of human forearm skin colour

  • 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

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

Effect of concentration and degree of saturation of topical fluocinonide formulations on in vitro membrane transport and in vivo availability on human skin

  • 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

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

Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioequivalence testing

  • Authors: Demana, Patrick H , Smith, Eric W , Walker, Roderick B , Haigh, John M , Kanfer, Isadore
  • Date: 1997
  • Language: English
  • Type: Article
  • Identifier: vital:6356 , http://hdl.handle.net/10962/d1006047
  • Description: The American FDA has recently released a Guidance document for topical corticosteroid bioequivalence testing. The purpose of this study was to evaluate the recommendations of this document for appropriateness. The new specifications require a dose-vasoconstriction response estimation by the use of a Minolta chromameter in a preliminary pilot study to determine the parameters for use in a pivotal bioequivalence study. Methods. The visually-assessed human skin blanching assay methodology routinely practiced in our laboratories was modified to comply with the requirements of the pilot study so that visual and chromameter data could be compared. Two different cream formulations, each containing 0.12% betamethasone 17-valerate, were used for this comparison. Results. Visual data showed the expected rank order of AUC values for most dose durations whereas the chromameter data did not show similar results. The expected rank order of AUC values for both chromameter and visual data was not observed at very short dose durations. In fitting the data to pharmacodynamic models, equivalent goodness of fit criteria were obtained when several different parameter estimates were used in the model definition, however the visual data were best described by the sigmoid E[subscript max] model while the chromameter data were best described by the simple E[subscript max] model. Conclusions. The E[subscript max] values predicted by the models were close to the observed values for both data sets and, in addition, excellent correlation between the AUC values and the maximum blanching response (R[subscript max]) (r > 0.95) was noted for both methods of assessment. The chromameter ED[subscript 50] values determined in this study were approximately 2 hours for both preparations. At this dose duration the instrument would not be sensitive enough to distinguish between weak blanching responses and normal skin for bioequivalence assessment purposes.
  • Full Text: false
  • Date Issued: 1997

Foam drug delivery in dermatology: beyond the scalp

  • 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.
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  • Date Issued: 2003

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

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

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

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 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
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