Comparative blanching activities of proprietary diflucortolone valerate topical preparations
- Authors: Coleman, Gerald L , Kanfer, Isadore , Haigh, John M
- Date: 1978
- Language: English
- Type: Article
- Identifier: vital:6350 , http://hdl.handle.net/10962/d1006032
- Description: The blanching activities and hence bioavailabilities of the cream, ointment and fatty ointment preparations of Nerisone and Temetex (diflucortolone valerate 0.1%) were evaluated using an occluded and unoccluded blanching assay. These products were compared to Synalar ointment and cream (fluocinolone acetonide 0.025%), established topical corticosteroid preparations. Statistical analysis showed no significant differences between similar formulations of diflucortolone valerate. Significant differences were noted between diflucortolone valerate and fluocinolone acetonide preparations.
- Full Text:
- Date Issued: 1978
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
Pharmacokinetics of phenylpropanolamine in humans after a single dose study
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6363 , http://hdl.handle.net/10962/d1006059
- Description: The pharmacokinetics of phenylpropanolamine have been studied in healthy human volunteers following the oral administration of an aqueous solution of the drug (50 mg/200 ml). Blood and urine samples collected throughout the trial were assayed using HPLC with UV detection. The drug was shown to be rapidly absorbed with a mean tmax of 1.47 ± 0.49 h and a mean elimination half-life of 4.0 ± 0.5 h. Phenylpropanolamine is predominantly excreted via the kidney with a mean renal clearance of 0.646 ± 0.089 liter/kg/h and 90.2 ± 1.7% excreted unchanged in the urine. The data were not well described using conventional one or two body compartment models. However, the incorporation of a discontinuous absorption phase into the models resulted in an improved overall fit with better characterisation of the absorption phase.
- Full Text:
- Date Issued: 1987
In vitro-in vivo evaluation of a sustained release phenylpropanolamine oral dosage form
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1982
- Language: English
- Type: Article
- Identifier: vital:6360 , http://hdl.handle.net/10962/d1006052
- Description: There is increasing interest in measuring pharmacokinetic parameters of phenylpropanolamine (PPA), a sympathomimetic amine used in over-the-counter nasal decongestants and anorectic formulations. A high pressure liquid chromatographic (HPLC) procedure was developed to enable direct ultraviolet detection of PPA, after extraction from serum and urine, without prior derivatization of the drug. This method was used to assay samples obtained from a bioavailability study of BUBtained-releasePPA tablets. The mean serum and urine profiles obtained are presented. The sustained-release tablets were subjected to dissolution testing utilizing the United States Pharmacopoeia (USP XIX) rotating basket method. An internal standard was incorporated into the dissolution fluid to enable direct analysis of the samples by HPLC. A comparison of three different dissolution fluid regimens was carried out to determine if release of the drug was affected by the change in pH of the medium and to select the most convenient method for the final dissolution studies. Some preliminary observations relating to correlations between rate of drug release from the sustained-release dosage form and percent drug absorbed are presented.
- Full Text:
- Date Issued: 1982
Determination of phenylpropanolamine in serum and urine by high performance liquid chromatography
- Authors: Dowse, Roslind , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6361 , http://hdl.handle.net/10962/d1006056
- Description: A high-performance liquid chromatographic analysis of phenylpropanolamine in human serum and urine without prior derivatization is presented. Using direct UV detection the method is sufficiently sensitive to detect 25 ng of drug/ml of serum or urine; the coefficients of variation at 25 ng/ml and 500 ng/ml were 5.16 and 2.12, respectively, in serum. The method involves serum and urine extraction at a basic pH with chloroform, a single back-extraction, and chromatography on a reverse-phase column. Serum and urine data following administration of a single 150-mg sustained-release tablet of phenylpropanolamine hydrochloride in 6 healthy volunteers demonstrates the suitability of the analytical method.
- Full Text:
- Date Issued: 1983
The simultaneous determination of trimethoprim, sulphamethoxazole and N4-acetylsulphamethoxazole in biological fluids by high pressure liquid chromatography
- Authors: Gochin, Rosa , Kanfer, Isadore , Haigh, John M
- Date: 1981
- Language: English
- Type: text , Article
- Identifier: vital:6364 , http://hdl.handle.net/10962/d1006064
- Description: The simultaneous determination of trimethoprim, sulphamethoxazole and N4-acetylsulphamethoxazole in serum and urine by high-performance liquid chromatography using sulphafurazole as internal standard is described. The separation was achieved on a reversed-phase column employing acetic acid-methanol as the mobile phase with spectrophotometric detection at 230 nm. Precise simultaneous quantitative analysis of the relative components has been achieved at levels of 0.1 μg/ml for both sulphamethoxazole and its N4-acetyl metabolite using 1 ml of serum or urine.
- Full Text:
- Date Issued: 1981
The human skin blanching assay for in vivo topical corticosteroid assessment. II. Subject- and observer-dependent variation in blanching responses
- Authors: Haigh, John M , Meyer, Eric , Smith, Eric W , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: text , Article
- Identifier: vital:6382 , http://hdl.handle.net/10962/d1006300
- Description: The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective.
- Full Text:
- Date Issued: 1997
Relative potencies of topical corticosteroid formulations
- Authors: Haigh, John M , Kanfer, Isadore , Meyer, Eric , Smith, Eric W
- Date: 1985
- Language: English
- Type: Article
- Identifier: vital:6375 , http://hdl.handle.net/10962/d1006291
- Description: It seems to us, and others (Burdick, 1974), that multiple reading times are essential to produce the response-time profile. Comparisons of potencies of topical corticosteroid formulations should only be made on the basis of area under the curve measurements and statistical treatment of all values obtained at each reading time throughout the course of the experiment.
- Full Text:
- Date Issued: 1985
Reply to correspondence: P.M. Gaylarde (1986) The human skin blanching assay—use and abuse
- Authors: Haigh, John M , Kanfer, Isadore , Meyer, Eric , Smith, Eric W
- Date: 1986
- Language: English
- Type: Article
- Identifier: vital:6376 , http://hdl.handle.net/10962/d1006293
- Description: Finally, we would like to assure Dr Gaylarde that we do not advocate the use of the human skin blanching assay. There are several other in vivo methods for determining corticosteroid activity which will provide equally meaningful results. What we are advocating is that if the human skin blanching assay is going to be used, then it should be used properly.
- Full Text:
- Date Issued: 1986
Assessment of topical corticosteroid preparations: the human skin-blanching assay
- Authors: Haigh, John M , Kanfer, Isadore
- Date: 1984
- Language: English
- Type: text , Article
- Identifier: vital:6374 , http://hdl.handle.net/10962/d1006284
- Description: (From the introduction) Since the introduction of topical corticosteroid formulations, their use has become widespread, being prescribed for a large variety of dermatological conditions. This widespread use has created a need for a reliable method of assessing the various dosage forms of these compounds. Clinical trials are laborious, costly and difficult to mount as well as being impractical for the screening of large numbers of drugs. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid preparations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between patients (Baker and Sattar, 1968). For these reasons a number of methods have been developed for the screening of novel corticosteroids and testing of topical corticosteroid formulations.
- Full Text:
- Date Issued: 1984
New developments in the methodology available for the assessment of topical corticosteroid-induced skin blanching
- Authors: Haigh, John M , Smith, Eric W , Maibach, Howard I
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6384 , http://hdl.handle.net/10962/d1006305
- Description: Since the publication of the previous edition of this book there have been considerable developments and controversy in the field of topical corticosteroid bioequivalence assessment. There has been considerable discussion in the literature concerning the use of the Minolta chromameter for the measurement of corticosteroid-induced skin blanching, as it is believed this instrument would produce more objective results than the visual grading procedure. These efforts culminated in the release of a guidance document from the Food and Drug Administration (FDA) detailing the procedures to be followed for the determination of topical corticosteroid bioequivalence using the chromameter. Since the promulgation of this document there have been challenges on the validity and scientific merit of the documented procedures, and recently the FDA itself conceded that it may be necessary to redefine some of the protocol evaluations. This chapter attempts to redefine the current standing of the two methods of response assessment.
- Full Text:
- Date Issued: 1998
The requirements for accurate analysis of pharmaceutical research at South African Universities
- Authors: Haigh, John M , Smith, Eric W
- Date: 1998
- Language: English
- Type: text , Article
- Identifier: vital:6367 , http://hdl.handle.net/10962/d1006067
- Description: International Pharmaceutical Abstracts is a valuable database for pharmaceutical research, although the multisiciplinary nature of this field implies that the database should only be the starting point of a search. This database is totally inappropriate for comparing outputs of individual pharmacy teaching institutions.
- Full Text:
- Date Issued: 1998
In vitro permeation of progesterone from a gel through the shed skin of three different snake species
- Authors: Haigh, John M , Beyssac, E , Chanet, L , Aiache, J M
- Date: 1998
- Language: English
- Type: Article
- Identifier: vital:6366 , http://hdl.handle.net/10962/d1006066
- Description: The in vitro diffusion of progesterone from a gel formulation using the European Pharmacopoeia method for transdermal dosage forms is described. The membranes used were the dorsal and ventral portions of the shed skin of three different species of snake. Considerable differences are apparent between the dorsal and ventral sites and between the different species of snake. The dorsal area shows better permeability for progesterone and the permeability order for the different species is python>cobra>viper. These differences may be due to the thickness of the skin and the hinge:scale ratio. The results indicate that shed snake skin is not a model membrane for human skin.
- Full Text:
- Date Issued: 1998
The human skin-blanching assay for in vitro topical corticosteroid assessment. I. Reproducibility of the assay
- Authors: Haigh, John M , Meyer, Eric , Smith, Eric W , Kanfer, Isadore
- Date: 1997
- Language: English
- Type: text , Article
- Identifier: vital:6381 , http://hdl.handle.net/10962/d1006299
- Description: The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective.
- Full Text:
- Date Issued: 1997
Topical corticosteroid-induced skin blanching measurement, eye or instrument?
- Authors: Haigh, John M , Smith, Eric W
- Date: 1991
- Language: English
- Type: Article
- Identifier: vital:6378 , http://hdl.handle.net/10962/d1006296
- Description: We have read with interest a recent critique of the human skin blanching assay. We are concerned about the accuracy of statements and the interpretation of results presented in this publication. Having successfully employed this bioassay for over 15 years, and having noted similar, productive usage of this optimized technique reported from laboratories worldwide, the negativism expressed in the critique could dissuade potential researchers from employing this extremely useful assay procedure.
- Full Text:
- Date Issued: 1991
Dilution of topical corticosteroid formulations
- Authors: Haigh, John M
- Date: 1988
- Language: English
- Type: text , Article
- Identifier: vital:6377 , http://hdl.handle.net/10962/d1006295
- Description: It has been a long-held concern of a number of people working in this field that some dermatologists prescribing a 1:10 dilution of a corticosteroid preparation such as Dermovate cream believe that the final product will be one tenth as efficacious and also produce one tenth of the side effects as the undiluted formulation. This is certainly not the case. Dermovate falls into the very potent category of topical corticosteroid preparations (as defined in the United Kingdom Monthly Index of Medical Specialities) and a 1:10 dilution falls into the potent category.
- Full Text:
- Date Issued: 1988
Complexes of mercury(II) and zinc(II) with primary aromatic amines
- Authors: Haigh, John M , Van Dam, M A , Thornton, D A
- Date: 1967
- Language: English
- Type: text , Article
- Identifier: vital:6370 , http://hdl.handle.net/10962/d1006072
- Description: A series of amine complexes has been prepared by reaction of zinc chloride and mercuric chloride with primary aromatic amines. A detailed assignment of the bands in the infra-red spectra of the complexes in the range 4000-625 cm [superscript]-1 is presented. The symmetric and asymmetric N-H stretching frequencies follow the relationship v(sym) = 345.5+ 0.876v(asym). The C-N stretching frequencies exhibit a linear relationship with the Hammett α-functions for the m- and p-substituted amines.
- Full Text:
- Date Issued: 1967
The selection and use of natural and synthetic membranes for in vitro diffusion experiments
- Authors: Haigh, John M , Smith, Eric W
- Date: 1994
- Language: English
- Type: text , Article
- Identifier: vital:6379 , http://hdl.handle.net/10962/d1006297
- Description: The following membranes are discussed: human skin; animal models (including mouse, hairless mouse, rat, guinea pig, rabbit, monkey, pig, shed snake skin, egg-shell membrane, and synthetic stratum corneum); and synthetic membranes (including cellulose media, filter membranes, and synthetic polymers). Membrane integrity and diffusive characteristics are also considered.
- Full Text:
- Date Issued: 1994
The effects of elevated and ambient temperature conditions on dilutions of fluocinolone acetonide ointment assessed using the human skin-blanching assay
- Authors: Haigh, John M , Smith, Eric W
- Date: 1995
- Language: English
- Type: text , Article
- Identifier: vital:6380 , http://hdl.handle.net/10962/d1006298
- Description: Topical corticosteroid formulations have been in use now for some 30 years and many methods are available for the in vivo assessment of these preparations. Of all the assays described in the literature, the one first advocated by McKenzie and Stoughton, the so-called vasoconstrictor assay, is one of the most reliable if performed by experienced researchers using - the optimised methodology. Topical application of corticosteroids produces a whitening (blanching) of the skin, the intensity of which is directly proportional to the clinical efficacy of the formulation. Assessment of the degree of blanching produced is therefore of use in determining the rate and extent of corticosteroid release' from the semi-solid base through the stratum corneum. Since it is the degree of blanching which is measured, we prefer to call this test the human skin blanching assay. Some of the main advantages of this assay technique are that normal healthy skin is used therefore persons with dermatological complaints are not compromised, it is not painful for the volunteers, it is non-invasive and several formulations can be evaluated simultaneously. Most commercially available topical corticosteroid preparations have been formulated in such a way as to provide optimum release of the active ingredient from the base through the stratum corneum. Despite this fact, many practitioners often prescribe dilutions of topical corticosteroid formulations, presumably in an effort to reduce the unwanted side effects. This could be problematic; dilution with an incompatible base could destroy the delivery environment thus considerably reducing the efficacy of the formulation. The method of dilution could also play a role in the suitability of the final preparation. The objective of this work was to determine the effects of two different dilutions of fluocinolone ointment at both ambient and elevated temperature on the blanching produced by the dilutions and, by inference, the relative clinical efficacies of these dilutions compared to the full strength product.
- Full Text:
- Date Issued: 1995
Can shed snakeskin be considered to be a model membrane for human stratum corneum?
- Authors: Haigh, John M , Beyssac, E , Aiache, J M
- Date: 1998
- Language: English
- Type: Article
- Identifier: vital:6383 , http://hdl.handle.net/10962/d1006303
- Description: Recently there has been some interest in the use of shed snake skin as a "model" membrane for in vitro diffusion studies. Many different species of snake have been utilised as well as different skin sites (dorsal and ventral). The species is usually named and sometimes the skin site is indicated butsometimes neither species nor skin site is reported. Insome countries it is particularly difficult to obtain human skin for in vitro experimentation and it is therefore important to have alternate biological or synthetic membranes which mimic human skin membranes for diffusion experiments. In South Africa. shed snake skin is easily obtainable from the many snake parks present in the country. Since snakes moult periodically, a single animal can provide repeated sheds, thus reducing interindividual variability. Skins can be obtained without injury to the animal and do not have to be subjected to chemical or heat stress prior to use. The epidermis is shed as a large intact sheet, thus a single snake skin can provide multiple samples. Shed snake skin is not a living tissue, can be stored for long periods at room temperature and is easily transported. Stored and fresh snake skins appear to show no differences in permeability. Since snake skin lacks hair follicles,the problems associated with the transfollicular route of penetration, which may be significant in mammalian skins, can be avoided.
- Full Text:
- Date Issued: 1998