Assessment of some variables affecting the blanching activity of betamethasone 17-valerate cream
- 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 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
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
Determination of erythromycin in serum and urine by high performance liquid chromatography with ultraviolet detection
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1985
- Language: English
- Type: text , Article
- Identifier: vital:6428 , http://hdl.handle.net/10962/d1006576
- Description: A high-performance liquid chromatographic analysis of erythromycin in human serum and urine with UV detection at 200 nm is presented. The method involves a solid-phase extraction procedure followed by a simple phase separation step and chromatography on a reversed-phase column. The method has sensitivity limits of 0.25 and 1.0 g/mL in serum and urine, respectively, and is sufficiently sensitive to monitor concentrations of erythromycin in human serum and urine after the administration of a single 500-mg erythromycin stearate tablet.
- Full Text:
- Date Issued: 1985
High performance liquid chromatographic analysis of oleandomycin in serum and urine
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1986
- Language: English
- Type: text , Article
- Identifier: vital:6429 , http://hdl.handle.net/10962/d1006590
- Description: The determination of oleandomycin in serum and urine by high-performance liquid chromatography using erythromycin as internal standard is described. The separation was achieved on a reversed-phase C 1 s column employing acetonitrile-0.05 A4 phosphate buffer (30:70), adjusted to pH 7.0, as the mobile phase with UV detection at 200 nm. A solid-phase extraction procedure, combined with a simple phaseseparation step was used prior to chromatographic analysis. Linear calibration curves were obtained in the concentration ranges 0.25-5.0 pg/ml (serum) and 1 .O-25.0 pg/ml (urine). Precise quantitative analysis has been achieved at these levels with relative standard deviations of < 5%.
- Full Text:
- Date Issued: 1986
Sensitive high-performance liquid chromatographic determination of cyclizine and its demethylated metabolite, norcyclizine, in biological fluids using coulometric detection
- Authors: Walker, Roderick B , Kanfer, Isadore
- Date: 1995
- Language: English
- Type: text , Article
- Identifier: vital:6452 , http://hdl.handle.net/10962/d1006640 , http://dx.doi.org/10.1016/0378-4347(95)00202-T
- Description: An accurate, sensitive, selective and reproducible high-performance liquid chromatographic method with coulometric detection for the determination of cyclizine and its inactive demethylated metabolite, norcyclizine, in biological fluids has been developed. The drugs were separated using a custom packed reversed-phase C18 analytical column and phosphate buffer (0.05 M, pH 3)-acetonitrile (7:3) as mobile phase. The dual electrode coulometric detector was operated in the "oxidative-screen" mode with the upstream electrode (detector 1) set at 0.55 V and the downstream electrode (detector 2) set at 0.90 V. Serum and urine samples were prepared for analysis by solid-phase extraction, followed by a simple phase-separation step. The limit of quantitation was 1 ng/ml for both cyclizine and norcyclizine in serum and urine.
- Full Text:
- Date Issued: 1995
Pharmacokinetics of cyclizine following intravenous administration to human volunteers
- Authors: Kanfer, Isadore , Walker, Roderick B
- Date: 1996
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184389 , vital:44214 , xlink:href="https://doi.org/10.1016/0928-0987(96)00177-7"
- Description: The pharmacokinetics of cyclizine, a piperazine derivative useful in the prevention and treatment of nausea and vomiting, was investigated in six healthy male volunteers following an intravenous bolus dose. The drug is extensively distributed with a mean volume of distribution of 16.50 ± 3.33 l/kg and a mean total clearance of 0.870 ± 0.105 l/h per kg. Urinary excretion data showed that less than one percent of the dose was excreted up to 36 h as unchanged drug in the urine. The extremely low mean renal clearance (0.005 ± 0.002 l/h per kg) for the parent drug comprised only a small proportion of total clearance indicating that urinary excretion of parent drug is not a major route of elimination for cyclizine. The drug appears to exhibit biexponential pharmacokinetics and has a terminal elimination half-life of approximately 13 h.
- Full Text:
- Date Issued: 1996
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
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
Analysis of macrolide antibiotics
- Authors: Kanfer, Isadore , Skinner, Michael F , Walker, Roderick B
- Date: 1998
- Language: English
- Type: Article , text
- Identifier: vital:7011 , http://hdl.handle.net/10962/d1008394 , http://www.sciencedirect.com/science/article/pii/S0021967398002763
- Description: The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included.
- Full Text:
- Date Issued: 1998
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
Application of reverse-flow micellar electrokinetic chromatography for the simultaneous determination of flavonols and terpene trilactones in Ginkgo biloba dosage forms
- Authors: Dubber, Mary-Jean , Kanfer, Isadore
- Date: 2006
- Language: English
- Type: text , Article
- Identifier: vital:6357 , http://hdl.handle.net/10962/d1006049
- Description:
A reverse-flow micellar electrokinetic chromatographic (RF-MEKC) method was developed for the simultaneous qualitative determination of 10 components consisting of the flavonol glycosides, rutin and quercitrin, the flavonol aglycones, isorhamnetin, kaempferol and quercetin, the terpene trilactones, ginkgolides A, B, C and J and the sesquiterpene, bilobalide. This method was used to fingerprint Ginkgo biloba solid oral dosage forms and validated for the quantitation of the marker compounds, rutin and quercetin in some commercial products. In addition to the usual variables, the influence of some essential background electrolyte (BGE) components such as sodium dodecyl sulphate (SDS) and
-cyclodextrin concentrations were investigated. A polyimide fused-silica square capillary column (75 μm I.D. × 360 μm O.D.) with a total length of 60.0 cm and effective length of 45.0 cm was used for the separation. The final BGE consisted of 20 mM phosphoric acid, 40 mM SDS and 12 mM -cyclodextrin (pH 2.2) using reverse polarity with a voltage of −17.5 kV. Samples were injected electrokinetically at −5 kV for 3 s for the qualitative analysis and hydrodynamically at 20 mbar for 0.6 s for the quantitative assay. The total run time was 22 min and the limits of detection were 3.13 μg/ml and 1.88 μg/ml for rutin and quercetin, respectively. Fingerprint profiles of the solid oral dosage forms and the results of the quantitative analysis indicated that there were major discrepancies in the marker content between products and illustrates the value of this method for use as a procedure to assess product quality of commercially available Ginkgo biloba products. - Full Text:
- Date Issued: 2006
Bioequivalence assessment of generic products an innovative South African approach
- Authors: Walker, Roderick B , Kanfer, Isadore , Skinner, Michael F
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184256 , vital:44194 , xlink:href="https://doi.org/10.1080/10601330500534014"
- Description: Concurrent with the implementation of new legislation mandating Generic Substitution in South Africa, a new set of guidelines for bioavailability and bioequivalence have been published. Since one of the main objectives of the new legislation in South Africa relating to Generic Substitution is to ensure that medicines of high quality, safety, and efficacy are made more accessible and more affordable to the wider public, the need to speed up approval of such multi-source products has become a regulatory priority. In order to facilitate this process, various bioequivalence issues have been addressed including important issues such as the acceptance criteria and associated bioequivalence intervals, use of a foreign reference product and the issue of assessing highly variable drugs (HVDs). In addition, dispensations have been made with respect to food effect assessment and variability relating to genetic polymorphism in drug metabolism (genotyping/phenotyping). Furthermore, the use of “old” biostudies submitted in support of an application is subject to expiry date. Acceptance of appropriate data requires that specific criteria such as Cmax and AUC, in addition to the usual considerations, also meet the limits specified by the particular registration authority of the country where such products are intended to be marketed. Generally, these limits require that the 90% confidence interval (CI) for AUC and Cmax test/reference ratios lies within the acceptance interval of 0.80–1.25 calculated using log-transformed data. While such acceptance criteria are, in general, ubiquitous, some differences in acceptance criteria do exist between various countries. The new guidelines for bioavailability/bioequivalence studies developed by the South African regulatory authority, the Medicines Control Council (MCC), makes provision for highly variable drugs and the use of a non-South African reference product. The MCC requires that the acceptance criterion for Cmax ratios be set at 0.75–1.33 while maintaining AUC ratios at 0.80–1.25 using a 90% CI. Furthermore, provision is made to apply scaling based on average bioequivalence assessment and, as an interim measure, consideration has also been given to the use of a foreign reference product provided that equivalence between that product and the innovator product currently available on the South African market can be shown using in vitro testing.
- Full Text:
- Date Issued: 2006
Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy
- Authors: Verbeeck, R K , Kanfer, Isadore , Walker, Roderick B
- Date: 2006
- Language: English
- Type: text , Article
- Identifier: vital:6445 , http://hdl.handle.net/10962/d1006632
- Description: In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution.
- Full Text:
- Date Issued: 2006
Sterols and sterolins in Hypoxis hemerocallidea (African potato)
- Authors: Nair, V D P , Kanfer, Isadore
- Date: 2008
- Language: English
- Type: text , Article
- Identifier: vital:6417 , http://hdl.handle.net/10962/d1006535
- Description: Commercially available health supplements and herbal remedies containing sterols and sterolins, either from African potato (Hypoxis hemerocallidea) alone, or whether enriched with sterols and sterolins, are claimed to be efficacious in the treatment of a variety of ailments. Sterols and sterolins in African potato are purported to be the relevant constituents that are required for the therapeutic claims of such products. A patent describing the extraction of sterolins from African potato plant material has claimed that approximately 9 mg sterolins can be isolated from 100 g of an enriched aqueous African potato extract. Our analysis of African potato plant material and its sterol and sterolin content, when similarly prepared, shows that the measureable content of sterols and sterolins in African potato is far less than the amounts of these compounds that have been claimed to be necessary for therapeutic benefit. We conclude that therapeutic claims relating to sterol and sterolin content in African potato are unsubstantiated, in view of the extremely low content of such compounds that we have isolated from our plant material, and in products containing African potato, or extracts thereof.
- Full Text:
- Date Issued: 2008
Rapid UPLC - MS/MS method for the determination of ketoprofen in human dermal microdialysis samples
- Authors: Tettey-Amlalo, Ralph N O , Kanfer, Isadore
- Date: 2009
- Language: English
- Type: text , Article
- Identifier: vital:6444 , http://hdl.handle.net/10962/d1006631
- Description: Dermal microdialysis (DMD) is a technique capable of determining the percutaneous penetration of drugs from topical formulations intended for local and/or regional activity. Typically, the concentrations of drug collected in dialysates are very low, generally in the ng/ml or even pg/ml range. An additional challenge is the very low volume of sample collected at each collection time and which can range from 1 to 30 μl only. Hence the objective was to develop and validate a rapid, accurate, precise, reproducible and highly sensitive LC–MS/MS method for the quantitative analysis of ketoprofen (KET) in dialystes following application of a topical gel product to the skin of human subjects. UPLC–MS/MS was used and KET was separated on an Acquity™ UPLC BEH C18 column (100 mm × 2.1 mm i.d., 1.7 μm) and analysed in negative-ion (NI) electrospray ionisation (ESI) mode. The mobile phase (MP) consisted of acetonitrile:methanol:water (60:20:20, v/v/v) under isocratic conditions at a flow rate of 0.3 ml/min. Samples were extracted using ethyl acetate with ibuprofen (IBU) as internal standard (IS) and the organic solvent was then evaporated to dryness and the residue re-constituted in methanol. 5 μl samples were injected and analysis was performed at ambient temperature 22 ± 0.5 °C. KET and IBU eluted at 1.07 and 1.49 min, respectively. KET and IBU responses were optimised at the transitions 253.00 > 209.00 and 205.00 > 161.00, respectively. Calibration curves were linear over the range 0.5–500 ng/ml with correlation coefficients > 0.999. The accuracy and precision of the method were found to be between 99.97% and 104.67% (R.S.D. < 2%) and the mean recovery of KET from normal saline was 88.03 ± 0.3% (R.S.D. < 2.20%). The LLOQ and LOD values were found to be 0.5 and 0.1 ng/ml respectively whereas the ULOD was set at 500 ng/ml. The method was successfully applied to determine the bioavailability of KET following application of topical KET gel, Fastum® gel, to the skin of human volunteers.
- Full Text:
- Date Issued: 2009
In Vitro Release Testing (IVRT) of Topical Hydrocortisone Acetate Creams: a novel approach using positive and negative controls
- Authors: Mudyahoto, Nyengeterai Amanda , Rath, Seeprarani , Ramanah, Ashmita , Kanfer, Isadore
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149849 , vital:38888 , dx.doi.org/10.14227/DT270120P6
- Description: The objective was to develop and validate an in vitro release testing (IVRT) method to assess the release of hydrocortisone acetate (HCA) from five topical formulations. A marketed generic cream containing 1% HCA was used as the reference product. Vertical diffusion cells (VDCs) were used to assess and compare the release rates of HCA from cream formulations containing 0.5%, 1%, and 1.5% HCA. The study describes a novel approach to test the discriminatory power by including both positive and negative controls to declare pharmaceutical equivalence or inequivalence. The validated method was found to be sensitive, linear, precise, reproducible, robust, and selective for the analysis of HCA from topical cream products. Equivalence or inequivalence was established based on SUPAC-SS acceptance criteria using a 90% CI with limits of 75–133.33%. The IVRT method was shown to have discriminatory ability to appropriately measure significant differences in drug release from various cream formulations. This approach also provides useful information for the future development of acceptable IVRT methods to assess topical dosage forms for local action containing different drugs.
- Full Text:
- Date Issued: 2020