A capillary zone electrophoresis (CZE) method for the determination of cyclizine hydrochloride in tablets and suppositories
- Mohammadi, I, Kanfer, Isadore, Walker, Roderick B
- Authors: Mohammadi, I , Kanfer, Isadore , Walker, Roderick B
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6406 , http://hdl.handle.net/10962/d1006479
- Description: Current compendial methods of assay for the analysis of cyclizine tablets involve the use of UV spectrophotometry. Since this is a non-selective technique its application to more complex dosage forms, such as suppositories, is unlikely to be appropriate. There is therefore a need for the development of a highly specific quantitative analytical method, such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). The latter technique was chosen in view of some specific advantages over HPLC, such as the use of relatively non-toxic aqueous buffers, as opposed to organic solvents, which obviates the use of expensive HPLC grade solvents making CE more cost effective. Cyclizine was analyzed in 50 mM phosphate buffer (pH 2.3) and run at an applied voltage 25 kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and samples were loaded hydrodynamically onto an uncoated fused-silica capillary (60 cm×50 mm i.d.). Chlorcyclizine was used as the internal standard and resolution of both compounds was achieved in less than 7 min. Stress testing was undertaken in order to investigate the appearance of breakdown products. The method has the requisite accuracy, selectivity, sensitivity and precision to assay cyclizine in tablets and suppositories. Degradation products resulting from the stress studies did not interfere with the detection of cyclizine and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2004
- Authors: Mohammadi, I , Kanfer, Isadore , Walker, Roderick B
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6406 , http://hdl.handle.net/10962/d1006479
- Description: Current compendial methods of assay for the analysis of cyclizine tablets involve the use of UV spectrophotometry. Since this is a non-selective technique its application to more complex dosage forms, such as suppositories, is unlikely to be appropriate. There is therefore a need for the development of a highly specific quantitative analytical method, such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). The latter technique was chosen in view of some specific advantages over HPLC, such as the use of relatively non-toxic aqueous buffers, as opposed to organic solvents, which obviates the use of expensive HPLC grade solvents making CE more cost effective. Cyclizine was analyzed in 50 mM phosphate buffer (pH 2.3) and run at an applied voltage 25 kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and samples were loaded hydrodynamically onto an uncoated fused-silica capillary (60 cm×50 mm i.d.). Chlorcyclizine was used as the internal standard and resolution of both compounds was achieved in less than 7 min. Stress testing was undertaken in order to investigate the appearance of breakdown products. The method has the requisite accuracy, selectivity, sensitivity and precision to assay cyclizine in tablets and suppositories. Degradation products resulting from the stress studies did not interfere with the detection of cyclizine and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2004
A stability-indicating HPLC assay with on-line clean-up for betamethasone 17-valerate in topical dosage forms
- Smith, Eric W, Haigh, John M, Kanfer, Isadore
- 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
- 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
A stability-indicating liquid chromatographic method for the analysis of erythromycin in stored biological fluids using amperometric detection
- Stubbs, Christopher, Haigh, John M, Kanfer, Isadore
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6430 , http://hdl.handle.net/10962/d1006592
- Description: A simple, sensitive and reliable high-performance liquid chromatographic procedure has been developed for the determination of erythromycin in human serum and urine using amperometric detection. A solid-phase extraction procedure was used followed by chromatography on a reverse-phase column. The mean recovery of erythromycin from serum and urine was 80%. This method allows both erythromycin and its principle degradation product, anhydroeythromycin, to be determined during a period of sample storage at 4 degree C and minus 15 degree C. The method is sufficiently sensitive and precise and is thus highly suited for use in both pharmacokinetic and stability studies.
- Full Text:
- Date Issued: 1987
- Authors: Stubbs, Christopher , Haigh, John M , Kanfer, Isadore
- Date: 1987
- Language: English
- Type: Article
- Identifier: vital:6430 , http://hdl.handle.net/10962/d1006592
- Description: A simple, sensitive and reliable high-performance liquid chromatographic procedure has been developed for the determination of erythromycin in human serum and urine using amperometric detection. A solid-phase extraction procedure was used followed by chromatography on a reverse-phase column. The mean recovery of erythromycin from serum and urine was 80%. This method allows both erythromycin and its principle degradation product, anhydroeythromycin, to be determined during a period of sample storage at 4 degree C and minus 15 degree C. The method is sufficiently sensitive and precise and is thus highly suited for use in both pharmacokinetic and stability studies.
- Full Text:
- Date Issued: 1987
African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia: an overview of evidence and pharmacology
- Mills, Edward, Cooper, Curtis, Seely, Dugald, Kanfer, Isadore
- Authors: Mills, Edward , Cooper, Curtis , Seely, Dugald , Kanfer, Isadore
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6401 , http://hdl.handle.net/10962/d1006337
- Description: In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment.
- Full Text:
- Date Issued: 2005
- Authors: Mills, Edward , Cooper, Curtis , Seely, Dugald , Kanfer, Isadore
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6401 , http://hdl.handle.net/10962/d1006337
- Description: In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment.
- Full Text:
- Date Issued: 2005
An LC-MS-MS method for the determination of cyclizine in human serum
- Mohammadi, Ali, Kanfer, Isadore, Sewram, V, Walker, Roderick B
- Authors: Mohammadi, Ali , Kanfer, Isadore , Sewram, V , Walker, Roderick B
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6408 , http://hdl.handle.net/10962/d1006481
- Description: Cyclizine is a piperazine derivative with anti-emetic activity that is useful in the prevention and treatment of nausea and vomiting associated with motion sickness. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the quantitation of cyclizine in serum. Sample pretreatment involved liquid-liquid extraction of 200 μl of serum with dichloromethane after the addition of 100 μl each of ammonium hydroxide and internal standard solutions. The extracts were analyzed by HPLC on a Luna ® C18 reversed-phase column and an ion-trap mass spectrometer with an electrospray interface. A limit of detection of 1 ng/ml was determined which allowed for the reliable measurement of cyclizine in the serum of human subjects. The method was found to be linear over the calibration range of 2.5-100 ng/ml. The applicability of this method was demonstrated by the analysis of serum obtained from a human volunteer following administration of a single 50 mg cyclizine hydrochloride tablet. The reported method was observed to have the necessary sensitivity, selectivity, precision and accuracy for monitoring cyclizine concentrations in human subjects following oral administration.
- Full Text:
- Date Issued: 2005
- Authors: Mohammadi, Ali , Kanfer, Isadore , Sewram, V , Walker, Roderick B
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6408 , http://hdl.handle.net/10962/d1006481
- Description: Cyclizine is a piperazine derivative with anti-emetic activity that is useful in the prevention and treatment of nausea and vomiting associated with motion sickness. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the quantitation of cyclizine in serum. Sample pretreatment involved liquid-liquid extraction of 200 μl of serum with dichloromethane after the addition of 100 μl each of ammonium hydroxide and internal standard solutions. The extracts were analyzed by HPLC on a Luna ® C18 reversed-phase column and an ion-trap mass spectrometer with an electrospray interface. A limit of detection of 1 ng/ml was determined which allowed for the reliable measurement of cyclizine in the serum of human subjects. The method was found to be linear over the calibration range of 2.5-100 ng/ml. The applicability of this method was demonstrated by the analysis of serum obtained from a human volunteer following administration of a single 50 mg cyclizine hydrochloride tablet. The reported method was observed to have the necessary sensitivity, selectivity, precision and accuracy for monitoring cyclizine concentrations in human subjects following oral administration.
- Full Text:
- Date Issued: 2005
Analysis of macrolide antibiotics
- Kanfer, Isadore, Skinner, Michael F, Walker, Roderick B
- 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
- 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
Application of reverse-flow micellar electrokinetic chromatography for the simultaneous determination of flavonols and terpene trilactones in Ginkgo biloba dosage forms
- Dubber, Mary-Jean, Kanfer, Isadore
- 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
- 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
Assessment of some variables affecting the blanching activity of betamethasone 17-valerate cream
- Magnus, Ashley D, Haigh, John M, Kanfer, Isadore
- Authors: Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1980
- Language: English
- Type: text , Article
- Identifier: vital:6396 , http://hdl.handle.net/10962/d1006320
- Description: The effect of concentration and occlusion time on the ability of Betnovate ® cream (betamethasone 17-valerate 0.1%) to produce skin blanching was assessed. Generally, increased concentration or occlusion time produce and increase in the degree of blanching observed, however, a plateau stage is eventually reached where no further increase of blanching occurs.
- Full Text:
- Date Issued: 1980
- Authors: Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1980
- Language: English
- Type: text , Article
- Identifier: vital:6396 , http://hdl.handle.net/10962/d1006320
- Description: The effect of concentration and occlusion time on the ability of Betnovate ® cream (betamethasone 17-valerate 0.1%) to produce skin blanching was assessed. Generally, increased concentration or occlusion time produce and increase in the degree of blanching observed, however, a plateau stage is eventually reached where no further increase of blanching occurs.
- Full Text:
- Date Issued: 1980
Assessment of topical corticosteroid preparations: the human skin-blanching assay
- Haigh, John M, Kanfer, Isadore
- 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
- 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
Bioequivalence assessment of generic products an innovative South African approach
- Walker, Roderick B, Kanfer, Isadore, Skinner, Michael F
- 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
- 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
Comparative bioavailability of some locally manufactured betamethasone valerate containing preparations
- Meyer, Eric, Haigh, John M, Kanfer, Isadore
- Authors: Meyer, Eric , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6399 , http://hdl.handle.net/10962/d1006326
- Description: The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application.
- Full Text:
- Date Issued: 1983
- Authors: Meyer, Eric , Haigh, John M , Kanfer, Isadore
- Date: 1983
- Language: English
- Type: Article
- Identifier: vital:6399 , http://hdl.handle.net/10962/d1006326
- Description: The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application.
- Full Text:
- Date Issued: 1983
Comparative blanching activities of proprietary diflucortolone valerate topical preparations
- Coleman, Gerald L, Kanfer, Isadore, Haigh, John M
- 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
- 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
Comparative blanching activities of some topical corticosteroid containing lotions
- Meyer, I, Kanfer, Isadore, Haigh, John M
- Authors: Meyer, I , Kanfer, Isadore , Haigh, John M
- Date: 1981
- Language: English
- Type: Article
- Identifier: vital:6398 , http://hdl.handle.net/10962/d1006324
- Description: The blanching activities of Betnovate and Celestoderm-V lotions (betamethasone-17-valerate, 0,1%) and Diprosone lotion (betamethasone dipropionate, 0,55%) were determined by measuring their ability to cause blanching of human skin after topical application. Betnovate and Celestoderm-V lotions produced almost identical blanching profiles. Diprosone lotion displayed a statistically significant superior blanching acitivity over both Betnovate and Celestoderm-V lotions over the whole timespan of the trial.
- Full Text:
- Date Issued: 1981
- Authors: Meyer, I , Kanfer, Isadore , Haigh, John M
- Date: 1981
- Language: English
- Type: Article
- Identifier: vital:6398 , http://hdl.handle.net/10962/d1006324
- Description: The blanching activities of Betnovate and Celestoderm-V lotions (betamethasone-17-valerate, 0,1%) and Diprosone lotion (betamethasone dipropionate, 0,55%) were determined by measuring their ability to cause blanching of human skin after topical application. Betnovate and Celestoderm-V lotions produced almost identical blanching profiles. Diprosone lotion displayed a statistically significant superior blanching acitivity over both Betnovate and Celestoderm-V lotions over the whole timespan of the trial.
- Full Text:
- Date Issued: 1981
Comparison of the blanching activities of Dermovate, Betnovate and Eumovate creams and ointments
- Meyer, Eric, Magnus, Ashley D, Haigh, John M, Kanfer, Isadore
- Authors: Meyer, Eric , Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1988
- Language: English
- Type: Article
- Identifier: vital:6393 , http://hdl.handle.net/10962/d1006315
- Description: The human skin blanching assay was used to determine the blanching activities of Dermovate, Betnovate and Eumovate creams and ointments. Dermovate was found to elicit a superior blanching response to Betnovate which in turn elicited a superior blanching response to Eumovate, except in the comparison of Betnovate and Eumovate ointments under occlusion. The importance of employing the correct methodology of the blanching assay is emphasized and the good correlation between the results of this study and clinical trials is indicated.
- Full Text: false
- Date Issued: 1988
- Authors: Meyer, Eric , Magnus, Ashley D , Haigh, John M , Kanfer, Isadore
- Date: 1988
- Language: English
- Type: Article
- Identifier: vital:6393 , http://hdl.handle.net/10962/d1006315
- Description: The human skin blanching assay was used to determine the blanching activities of Dermovate, Betnovate and Eumovate creams and ointments. Dermovate was found to elicit a superior blanching response to Betnovate which in turn elicited a superior blanching response to Eumovate, except in the comparison of Betnovate and Eumovate ointments under occlusion. The importance of employing the correct methodology of the blanching assay is emphasized and the good correlation between the results of this study and clinical trials is indicated.
- Full Text: false
- Date Issued: 1988
Determination of erythromycin in serum and urine by high performance liquid chromatography with ultraviolet detection
- Stubbs, Christopher, Haigh, John M, Kanfer, Isadore
- 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
- 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
Determination of phenylpropanolamine in serum and urine by high performance liquid chromatography
- Dowse, Roslind, Haigh, John M, Kanfer, Isadore
- 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
- 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
Evaluation of the proposed FDA pilot-dose response methodology for topical corticosteroid bioeqivalence testing [authors' reply in Letters to the Editor]
- Smith, Eric W, Walker, Roderick B, Haigh, John M, Kanfer, Isadore
- 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
- 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
- Demana, Patrick H, Smith, Eric W, Walker, Roderick B, Haigh, John M, Kanfer, Isadore
- 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
- 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
Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy
- Verbeeck, R K, Kanfer, Isadore, Walker, Roderick B
- 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
- 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
High performance liquid chromatographic analysis of oleandomycin in serum and urine
- Stubbs, Christopher, Haigh, John M, Kanfer, Isadore
- 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
- 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