The development and assessment of both a separate, once-daily modified release matrix formulation of metoprolol tartrate and a combination formulation with hydrochlorothiazide
- Authors: Arjun, Jessica
- Date: 2001
- Subjects: Metoprolol -- Controlled release , Chlorothiazide -- Controlled release , Diuretics , Hypertension -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3742 , http://hdl.handle.net/10962/d1003220 , Metoprolol -- Controlled release , Chlorothiazide -- Controlled release , Diuretics , Hypertension -- Treatment
- Description: The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. This research focused on the development of a once daily dosage form that could be used for the treatment of hypertension. Both a separate sustained release dosage of metoprolol tartrate and a combination dosage form that included both an immediate release hydrochlorothiazide and a sustained release metoprolol component, were developed and evaluated. A matrix tablet, consisting of an ethylcellulose ranulation of metoprolol tartrate compressed into a hydrophilic hydroxypropyl methylcellulose polymer matrix, effectively sustained metoprolol release over a 22-hour experimental period. A multiparticulate combination dosage form that consisted of six coated mini matrix tablets of metoprolol and a powder blend of hydrochlorothiazide packed into a gelatin capsule, displayed zero order release kinetics for metoprolol release over 22 hours (r2=0.9946). The release of hydrochlorothiazide was found to be comparable to that of a commercially available product tested. Differential Scanning Calorimetry was used to identify possible incompatibilities between MPTA and excipients initially, and long term stability testing was used to assess to behaviour of the dosage form. Dissolution testing of the dosage forms was performed using USP Apparatus III, which was found to be more discriminating between the batches assessed. Dissolution curves were evaluated for similarity and difference using f1 and f2 fit factors. Samples were analyzed using a high performance liquid chromatographic method that was developed and validated for the simultaneous determination of the compounds of interest. Various factors influencing drug release from the developed dosage forms were assessed and recommendations for further optimization of the formulation are made. Factors evaluated included the quantity of granulating fluid, matrix polymer content, drug load and process variables, including drying time and compression force. The influence of various coating levels on drug release was assessed and none of the levels assessed were found to adequately retarded drug release over a 22-hour period. Combinations of tablets coated to different levels allowed for the successful development of a sustained release metoprolol component, which could be included into the combination dosage form.
- Full Text:
- Date Issued: 2001
- Authors: Arjun, Jessica
- Date: 2001
- Subjects: Metoprolol -- Controlled release , Chlorothiazide -- Controlled release , Diuretics , Hypertension -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3742 , http://hdl.handle.net/10962/d1003220 , Metoprolol -- Controlled release , Chlorothiazide -- Controlled release , Diuretics , Hypertension -- Treatment
- Description: The use of controlled release dosage forms has increased significantly in recent years as they result in increased patient compliance and higher therapeutic efficiency. This research focused on the development of a once daily dosage form that could be used for the treatment of hypertension. Both a separate sustained release dosage of metoprolol tartrate and a combination dosage form that included both an immediate release hydrochlorothiazide and a sustained release metoprolol component, were developed and evaluated. A matrix tablet, consisting of an ethylcellulose ranulation of metoprolol tartrate compressed into a hydrophilic hydroxypropyl methylcellulose polymer matrix, effectively sustained metoprolol release over a 22-hour experimental period. A multiparticulate combination dosage form that consisted of six coated mini matrix tablets of metoprolol and a powder blend of hydrochlorothiazide packed into a gelatin capsule, displayed zero order release kinetics for metoprolol release over 22 hours (r2=0.9946). The release of hydrochlorothiazide was found to be comparable to that of a commercially available product tested. Differential Scanning Calorimetry was used to identify possible incompatibilities between MPTA and excipients initially, and long term stability testing was used to assess to behaviour of the dosage form. Dissolution testing of the dosage forms was performed using USP Apparatus III, which was found to be more discriminating between the batches assessed. Dissolution curves were evaluated for similarity and difference using f1 and f2 fit factors. Samples were analyzed using a high performance liquid chromatographic method that was developed and validated for the simultaneous determination of the compounds of interest. Various factors influencing drug release from the developed dosage forms were assessed and recommendations for further optimization of the formulation are made. Factors evaluated included the quantity of granulating fluid, matrix polymer content, drug load and process variables, including drying time and compression force. The influence of various coating levels on drug release was assessed and none of the levels assessed were found to adequately retarded drug release over a 22-hour period. Combinations of tablets coated to different levels allowed for the successful development of a sustained release metoprolol component, which could be included into the combination dosage form.
- Full Text:
- Date Issued: 2001
Pineal-adrenal gland interactions in search of an anti-stressogenic role for melatonin
- Authors: Van Wyk, Elizabeth Joy
- Date: 1993
- Subjects: Pineal gland -- Secretions , Melatonin , Adrenal glands , Pineal gland -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4054 , http://hdl.handle.net/10962/d1004115 , Pineal gland -- Secretions , Melatonin , Adrenal glands , Pineal gland -- Research
- Description: The multiple functions of the pineal gland have been collectively interpreted as constituting a general anti-stressogenic role. The adrenal glands play a central role in maintaining homeostasis. The major neuroendocrine consequence of long-term stress is elevated circulating glucocorticoid levels. In this study, the effect of chronic, oral hydrocortisone treatment on pineal biochemistry was investigated in male Wi star rats of the albino strain. The results show that seven days of oral hydrocortisone treatment endows the pineal gland with the ability to increase melatonin synthesis in organ culture. The increase is accompanied by a rise in NAT activity, cyclic AMP levels and enhanced specific binding to the pineal B-adrenergic receptors. It appears that hydrocortisone sensitizes the pineal gland to stimulation by B-adrenergic agonists. thus rendering the pineal more responsive to B-adrenergic agonists. Further studies were directed at demonstrating an anti-stressogenic function for the pineal gland by investigating whether the principal pineal indole, melatonin. could protect against the deleterious effects of elevated. circulating drocortisone levels. The results show that chronic, oral hydrocortisone treatment significantly increases liver tryptophan pyrrolase activity. The catabolism of tryptophan by tryptophan pyrrolase is an important determinant of tryptophan availability to the brain, and therefore, brain serotonin levels. The findings show that melatonin inhibits basal and hydrocortisone-stimulated liver tryptophan pyrrolase apoenzyme activity in a dose-dependent manner. This inhibition suggests that melatonin may protect against excessive loss of tryptophan from circulation and against deficiencies in the cerebral serotinergic system which are associated with mood and behavioural disorders. It was shown that another deleterious effect of chronic hydrocortisone treatment is a significant increase in the number of glutamate receptors in the forebrain of male Wistar rats. The increase in receptor number observed in this study is probably due to an increase in the synthesis of glutamate receptors and is associated with a marked reduction in the affinity of the glutamate receptors for glutamate. possible to demonstrate an receptor number or the For practical reasons, it was not effect of melatonin on either glutamate affinity of glutamate receptors for glutamate in rat forebrain membranes. In view of the neurotoxic effect of glutamate in the eNS, the functional significance of recently described glutamate receptors in the pineal gland was investigated. The results show that 10-4 M glutamate significantly inhibits the isoprenaline-stimulated synthesis of N-acetylserotonin and melatonin in organ culture when the pineal glands were pre-incubated with glutamate for 4 hours prior to stimulation with isoprenalin and when glutamate and isoprenaline were administered together in vitro. GABA, a glutamate metabolite could not mimic the decrease in isoprenalinestimulated melatonin, and it is likely that the observed effects were directly attributed to glutamate. Incubation of the pineal gland with 10-4 M glutamate in organ culture did not affect HIOMT activity in pineal homogenates, but significantly elevated both basal and isoprenaline-stimulated NAT activity. It was concluded that glutamate only inhibits melatonin synthesis in intact pineal glands and not in pineal homogenates. The present study has provided further support for an interaction between the pineal and the adrenal glands. There is an ever increasing likelihood that melatonin is an anti-stressogenic hormone and that the pineal gland may have a protective role to play in the pathology of stress-related diseases.
- Full Text:
- Date Issued: 1993
- Authors: Van Wyk, Elizabeth Joy
- Date: 1993
- Subjects: Pineal gland -- Secretions , Melatonin , Adrenal glands , Pineal gland -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4054 , http://hdl.handle.net/10962/d1004115 , Pineal gland -- Secretions , Melatonin , Adrenal glands , Pineal gland -- Research
- Description: The multiple functions of the pineal gland have been collectively interpreted as constituting a general anti-stressogenic role. The adrenal glands play a central role in maintaining homeostasis. The major neuroendocrine consequence of long-term stress is elevated circulating glucocorticoid levels. In this study, the effect of chronic, oral hydrocortisone treatment on pineal biochemistry was investigated in male Wi star rats of the albino strain. The results show that seven days of oral hydrocortisone treatment endows the pineal gland with the ability to increase melatonin synthesis in organ culture. The increase is accompanied by a rise in NAT activity, cyclic AMP levels and enhanced specific binding to the pineal B-adrenergic receptors. It appears that hydrocortisone sensitizes the pineal gland to stimulation by B-adrenergic agonists. thus rendering the pineal more responsive to B-adrenergic agonists. Further studies were directed at demonstrating an anti-stressogenic function for the pineal gland by investigating whether the principal pineal indole, melatonin. could protect against the deleterious effects of elevated. circulating drocortisone levels. The results show that chronic, oral hydrocortisone treatment significantly increases liver tryptophan pyrrolase activity. The catabolism of tryptophan by tryptophan pyrrolase is an important determinant of tryptophan availability to the brain, and therefore, brain serotonin levels. The findings show that melatonin inhibits basal and hydrocortisone-stimulated liver tryptophan pyrrolase apoenzyme activity in a dose-dependent manner. This inhibition suggests that melatonin may protect against excessive loss of tryptophan from circulation and against deficiencies in the cerebral serotinergic system which are associated with mood and behavioural disorders. It was shown that another deleterious effect of chronic hydrocortisone treatment is a significant increase in the number of glutamate receptors in the forebrain of male Wistar rats. The increase in receptor number observed in this study is probably due to an increase in the synthesis of glutamate receptors and is associated with a marked reduction in the affinity of the glutamate receptors for glutamate. possible to demonstrate an receptor number or the For practical reasons, it was not effect of melatonin on either glutamate affinity of glutamate receptors for glutamate in rat forebrain membranes. In view of the neurotoxic effect of glutamate in the eNS, the functional significance of recently described glutamate receptors in the pineal gland was investigated. The results show that 10-4 M glutamate significantly inhibits the isoprenaline-stimulated synthesis of N-acetylserotonin and melatonin in organ culture when the pineal glands were pre-incubated with glutamate for 4 hours prior to stimulation with isoprenalin and when glutamate and isoprenaline were administered together in vitro. GABA, a glutamate metabolite could not mimic the decrease in isoprenalinestimulated melatonin, and it is likely that the observed effects were directly attributed to glutamate. Incubation of the pineal gland with 10-4 M glutamate in organ culture did not affect HIOMT activity in pineal homogenates, but significantly elevated both basal and isoprenaline-stimulated NAT activity. It was concluded that glutamate only inhibits melatonin synthesis in intact pineal glands and not in pineal homogenates. The present study has provided further support for an interaction between the pineal and the adrenal glands. There is an ever increasing likelihood that melatonin is an anti-stressogenic hormone and that the pineal gland may have a protective role to play in the pathology of stress-related diseases.
- Full Text:
- Date Issued: 1993
Topical immunotherapy for Pseudomonas keratitis : use of antilipopolyssacharide plasma
- Authors: Rauch, Andrew Johan
- Date: 1984 , 2013-03-13
- Subjects: Pseudomonas infections , Immunotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3817 , http://hdl.handle.net/10962/d1004910 , Pseudomonas infections , Immunotherapy
- Description: Pseudomonas aeruginosa is an opportunistic pathogen capable of infecting the human cornea. Such infections are difficult to treat, and are often fulminative, in that the infected eye is lost, or severely scarred. The use of alternative therapeutic agents has been necessitated by the frequent failure of conventional antibiotic therapy. Equine hyperimmune antilipopolysaccharide plasma (Anti-LPS) was obtained by the plasmapheresis of suitably immunized horses. The plasma contained 1,O- 1 ,5g/ml of LPS-precipitible IgG antibodies. Topical administration of Anti-LPS as a lavage was shown to be effective against Pseudomonas keratitis in rabbits and guinea pigs. Subsequent use of topical corticosteroids was found to further reduce corneal pathology. The improvement noted in these experimental infections involved all three parameters measured, area of keratitis, depth of lesion, and degree of vascularization. In vitro , Anti-LPS was shown to be rapidly bactericidal for Gram negative bacteria. The plasma can therefore be said to have a dual mechanism of action: antitoxic, and antibacterial. Ocular administration of Anti-LPS, by both the topical and subconjunctival routes, was well tolerated by both rabbits and baboons. In conclusion, Anti-LPS is a potentially useful immunotherapeutic agent with many applications in both veteriary and human medicine, particularly in the treatment of surface infections involving antibiotic-resistant Gram negative bacteria , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
- Authors: Rauch, Andrew Johan
- Date: 1984 , 2013-03-13
- Subjects: Pseudomonas infections , Immunotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3817 , http://hdl.handle.net/10962/d1004910 , Pseudomonas infections , Immunotherapy
- Description: Pseudomonas aeruginosa is an opportunistic pathogen capable of infecting the human cornea. Such infections are difficult to treat, and are often fulminative, in that the infected eye is lost, or severely scarred. The use of alternative therapeutic agents has been necessitated by the frequent failure of conventional antibiotic therapy. Equine hyperimmune antilipopolysaccharide plasma (Anti-LPS) was obtained by the plasmapheresis of suitably immunized horses. The plasma contained 1,O- 1 ,5g/ml of LPS-precipitible IgG antibodies. Topical administration of Anti-LPS as a lavage was shown to be effective against Pseudomonas keratitis in rabbits and guinea pigs. Subsequent use of topical corticosteroids was found to further reduce corneal pathology. The improvement noted in these experimental infections involved all three parameters measured, area of keratitis, depth of lesion, and degree of vascularization. In vitro , Anti-LPS was shown to be rapidly bactericidal for Gram negative bacteria. The plasma can therefore be said to have a dual mechanism of action: antitoxic, and antibacterial. Ocular administration of Anti-LPS, by both the topical and subconjunctival routes, was well tolerated by both rabbits and baboons. In conclusion, Anti-LPS is a potentially useful immunotherapeutic agent with many applications in both veteriary and human medicine, particularly in the treatment of surface infections involving antibiotic-resistant Gram negative bacteria , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
Religious orders and personal and group attitudes and values
- Authors: Wright, Beryl
- Date: 1970
- Subjects: Church and social problems -- South Africa , Christians -- South Africa -- Grahamstown -- Attitudes
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:3358 , http://hdl.handle.net/10962/d1007685 , Church and social problems -- South Africa , Christians -- South Africa -- Grahamstown -- Attitudes
- Description: From Introduction: For many years I have been interested in the relationship between ethical and moral attitudes and values and religious belief. I became aware of a conflict in attitudes concerning the role of the Church in society as a member of the Methodist Church, and this stimulated me to study seriously the role of the Church in present day society. I found that members of the Wesley Guild, of which I myself was a member, conceived of the Guild in three forms: (a) as a social club; (b) as an institution for training in Christian service, both at the level of spiritual belief and practice and at the level of practical help to those in human need; (c) as an assooiation where individual spiritual values are fostered. Members differed in their view of the Guild, some seeing it in terms of all three enumerated forms, others emphasising one or two of these forms. This induced tension within the Guild. Wider observation led me to the view that this diffused concept of the Church and its functions was not peculiar to the Wesley Guild. It seemed to be general to the South African Church. I became confirmed in this view when, as a student at Rhodes University, I found that many theological students of different denominations shared it.
- Full Text:
- Date Issued: 1970
- Authors: Wright, Beryl
- Date: 1970
- Subjects: Church and social problems -- South Africa , Christians -- South Africa -- Grahamstown -- Attitudes
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:3358 , http://hdl.handle.net/10962/d1007685 , Church and social problems -- South Africa , Christians -- South Africa -- Grahamstown -- Attitudes
- Description: From Introduction: For many years I have been interested in the relationship between ethical and moral attitudes and values and religious belief. I became aware of a conflict in attitudes concerning the role of the Church in society as a member of the Methodist Church, and this stimulated me to study seriously the role of the Church in present day society. I found that members of the Wesley Guild, of which I myself was a member, conceived of the Guild in three forms: (a) as a social club; (b) as an institution for training in Christian service, both at the level of spiritual belief and practice and at the level of practical help to those in human need; (c) as an assooiation where individual spiritual values are fostered. Members differed in their view of the Guild, some seeing it in terms of all three enumerated forms, others emphasising one or two of these forms. This induced tension within the Guild. Wider observation led me to the view that this diffused concept of the Church and its functions was not peculiar to the Wesley Guild. It seemed to be general to the South African Church. I became confirmed in this view when, as a student at Rhodes University, I found that many theological students of different denominations shared it.
- Full Text:
- Date Issued: 1970
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