Comparative bioavailability and ranking of topical corticosteroid formulations
- Authors: Meyer, Eric
- Date: 1985
- Subjects: Adrenocortical hormones -- Therapeutic use Drugs -- Bioavailability Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3732 , http://hdl.handle.net/10962/d1001471
- Description: Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
- Full Text:
- Authors: Meyer, Eric
- Date: 1985
- Subjects: Adrenocortical hormones -- Therapeutic use Drugs -- Bioavailability Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3732 , http://hdl.handle.net/10962/d1001471
- Description: Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
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Biopharmaceutics of phenylpropanolamine
- Authors: Dowse, Roslind
- Date: 1984
- Subjects: Biopharmaceutics Pharmacokinetics Phenylpropanolamine Pharmacology High performance liquid chromatography
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3818 , http://hdl.handle.net/10962/d1004915
- Description: Phenylpropanolamine (PPA), a sympathomimetic amine, has been widely used over the past 40 years as a decongestant and, in much larger dosages, as an appetite suppressant. Considerable interest has recently been shown in this drug due to its increasing popularity as an over-the-counter anorectic agent. Much controversy exists concerning the unfavourable side-effects of PPA resulting from the higher doses required for appetite suppression and the potential of this drug for abuse. A literature search revealed a paucity of information concerning the determination of PPA in biological fluids and, most noticeably, on the pharmacokinetics of this drug. An original method for determining PPA in serum and urine using high performance liquid chromatography (HPLC) which has increased sensitivity over other published HPLC methods is presented here. The simplicity of the extraction from biological fluids and subsequent determination by HPLC, enables concentrations of PPA to be monitored after a single dose of the drug. This method is therefore readily applicable to bioavailability and pharmacokinetic studies. The dissolution profiles of 4 sustained-release formulations of PPA were determined in a modified USP rotating paddle apparatus and the samples analysed using HPLC. A mathematical equation was applied to these data which are expressed in terms of dissolution parameters. Oral test dosage forms and solutions of PPA were investigated in bioavailability trials using the developed HPLC method to analyse the urine and serum samples. Linear one body compartment kinetics were assumed and the WagnerNelson method used to transform in vivo serum data to absorption plots which were then fitted to the well known Weibull equation. In order to more appropriately characterize the kinetic processes of absorption, distribution and elimination, a more complex model was utilized which involved numerical integration of a series of differential equations. The data were fitted to these models using nonlinear regression techniques. The pharmacokinetics of PPA are shown to exhibit some evidence of nonlinearity. The absorption of the drug appears to be di scontinuous and PPA seems to favour a two body compartment model.
- Full Text:
- Authors: Dowse, Roslind
- Date: 1984
- Subjects: Biopharmaceutics Pharmacokinetics Phenylpropanolamine Pharmacology High performance liquid chromatography
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3818 , http://hdl.handle.net/10962/d1004915
- Description: Phenylpropanolamine (PPA), a sympathomimetic amine, has been widely used over the past 40 years as a decongestant and, in much larger dosages, as an appetite suppressant. Considerable interest has recently been shown in this drug due to its increasing popularity as an over-the-counter anorectic agent. Much controversy exists concerning the unfavourable side-effects of PPA resulting from the higher doses required for appetite suppression and the potential of this drug for abuse. A literature search revealed a paucity of information concerning the determination of PPA in biological fluids and, most noticeably, on the pharmacokinetics of this drug. An original method for determining PPA in serum and urine using high performance liquid chromatography (HPLC) which has increased sensitivity over other published HPLC methods is presented here. The simplicity of the extraction from biological fluids and subsequent determination by HPLC, enables concentrations of PPA to be monitored after a single dose of the drug. This method is therefore readily applicable to bioavailability and pharmacokinetic studies. The dissolution profiles of 4 sustained-release formulations of PPA were determined in a modified USP rotating paddle apparatus and the samples analysed using HPLC. A mathematical equation was applied to these data which are expressed in terms of dissolution parameters. Oral test dosage forms and solutions of PPA were investigated in bioavailability trials using the developed HPLC method to analyse the urine and serum samples. Linear one body compartment kinetics were assumed and the WagnerNelson method used to transform in vivo serum data to absorption plots which were then fitted to the well known Weibull equation. In order to more appropriately characterize the kinetic processes of absorption, distribution and elimination, a more complex model was utilized which involved numerical integration of a series of differential equations. The data were fitted to these models using nonlinear regression techniques. The pharmacokinetics of PPA are shown to exhibit some evidence of nonlinearity. The absorption of the drug appears to be di scontinuous and PPA seems to favour a two body compartment model.
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The comparative bioavailability and in vitro assessment of solid oral dosage forms of paracetamol
- Authors: Braae, Karen
- Date: 1981 , 2013-04-02
- Subjects: Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3827 , http://hdl.handle.net/10962/d1006288 , Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Description: The dissolution profiles of eight lots of paracetamol tablets representing seven different tablet brands are determined in a USP rotating basket assembly and a stationary basket-rotating paddle apparatus. The in vitro data are expressed in terms of dissolution parameters and inter-tablet differences are assessed statistically using analysis of variance (ANOVA) and the Scheffe test. Highly significant differences are observed between a number of the tablets at the 95% confidence level. Representative tablets from the dissolution rate study and a control dose of paracetamol dissolved in water are subsequently investigated in a 4 x 4 latin square design bioavailability trial. Serum and urine samples are collected and assayed for paracetamol alone (serum) and together with its metabolites (urine) by means of high pressure liquid chromatography. The in vivo data are expressed in terms of bioavailability parameters and differences between the test doses are assessed by means of ANOVA. No significant differences are observed between the dosage forms at the 95% confidence level.
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- Authors: Braae, Karen
- Date: 1981 , 2013-04-02
- Subjects: Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3827 , http://hdl.handle.net/10962/d1006288 , Acetaminophen , Bioavailability , Drugs -- Bioavailability , Drugs -- Dosage forms , Analysis of variance
- Description: The dissolution profiles of eight lots of paracetamol tablets representing seven different tablet brands are determined in a USP rotating basket assembly and a stationary basket-rotating paddle apparatus. The in vitro data are expressed in terms of dissolution parameters and inter-tablet differences are assessed statistically using analysis of variance (ANOVA) and the Scheffe test. Highly significant differences are observed between a number of the tablets at the 95% confidence level. Representative tablets from the dissolution rate study and a control dose of paracetamol dissolved in water are subsequently investigated in a 4 x 4 latin square design bioavailability trial. Serum and urine samples are collected and assayed for paracetamol alone (serum) and together with its metabolites (urine) by means of high pressure liquid chromatography. The in vivo data are expressed in terms of bioavailability parameters and differences between the test doses are assessed by means of ANOVA. No significant differences are observed between the dosage forms at the 95% confidence level.
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Development of a high pressure liquid chromatographic method for the simultaneous analysis of sulphamethoxazole and trimethoprim and its application to biological fluids and dissolution rate studies on solid oral dosage forms
- Authors: Gochin, Rosa
- Date: 1980
- Subjects: High performance liquid chromatography , Body fluids -- Analysis , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3735 , http://hdl.handle.net/10962/d1001524
- Description: Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
- Full Text:
- Authors: Gochin, Rosa
- Date: 1980
- Subjects: High performance liquid chromatography , Body fluids -- Analysis , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3735 , http://hdl.handle.net/10962/d1001524
- Description: Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
- Full Text: