The solubility enhancement and the stability assessment of rifampicin, isoniazid and pyrazinamide in aqueous media
- Authors: Chen, Yu-Jen
- Date: 2000
- Subjects: Gel permeation chromatography , Rifampin , Isoniazid , Pyridazines
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4346 , http://hdl.handle.net/10962/d1005009 , Gel permeation chromatography , Rifampin , Isoniazid , Pyridazines
- Description: Tuberculosis (TB) is a highly contagious disease caused by the bacterium known as Mycobacterium tuberculosis which is widely spread in South Africa, especially in the rural areas of the Western Province. Rifampicin, isoniazid and pyrazinamide are the three most effective drugs against this organism. However, most of the current commercial anti-TB formulations are inconvenient to administrate. This results in patient non-compliance which has increased with incomplete tuberculosis treatment and further has intensified the mortality rate. The matter is especially severe amongst the paediatric and geriatric patients. Therefore, creating a "user-friendly" but non-alcoholic liquid formulation should improve the whole situation. The key to a successful formulation relies on sufficient concentrations of the drugs within the formulation together with acceptable stability of these drugs. Therefore, during the pre-formulation stage, the solubility and stability studies of rifampicin, isoniazid and pyrazinamide are to be conducted. Rifampicin, isoniazid and pyrazinamide were fully characterized and identified by means of spectroscopic and thermal techniques. A HPLC method for simultaneous analysis of the three drugs was developed and validated. This HPLC method was employed for all the solubility and stability assessments. Unbuffered HPLC water of pH value 7.01 was chosen as the aqueous solvent. This was decided after the stability of rifampicin, isoniazid and pyrazinamide was studied at a pH range of 2 to 10. The solubility and the stability studies of rifampicin, isoniazid, pyrazinamide, rifampicin with isoniazid, rifampicin with pyrazinamide, isoniazid with pyrazinamide and rifampicin combined with both isoniazid and pyrazinamide were performed in the presence of various agents. These agents can be categorized into three groups: the surfactants (poloxamer 188, poloxamer 407 and sorbitol) which could increase the intrinsic solubility or the drugs by altering the surface tensions of the aqueous solution medium, the suspending agents (carbopol 934 and carbopol 974P) which could enable the amount of dosage required to be homogeneously suspended in the formulation without considering the low intrinsic solubility factor of the drugs, and the complexing agents (ß-cyclodextrin, hydroxypropyl-ß-cyclodextrin and -cyclodextrin) which could initiated the inclusion complex between the host cyclodextrin and the drugs, thus further enhance the solubility of the drugs . The stability assessments were performed after 7-days stability trail with the HPLC method developed. Each drug/combination of drugs were stored in closed ampoules and subjected to 25, 40 and 60° C with or without nitrogen flushing while in the presence of the above mentioned agents. While assessing the solubility/stability of the drugs in the presence of the above mentioned surfactants, the phase-solubility curves indicate that both rifampicin and pyrazinamide fail to achieve the desired concentration. Moreover, the stability-time plots clearly indicate that these surfactants fail to enhance the general stabilities of the drugs. When the stabilizing effects of the above mentioned suspending agents were investigated, it was found that although the desired concentration could be easily accomplished by suspending the drug in the aqueous carbopol solutions, the stabilities of the different drug combinations were still below the regulatory level. Cyclodextrins are well known to form inclusion complexes with less polar drug molecules. The inclusion complexation could enhance both the solubility and the stability of the included drug molecules. The computer force field generated models of the cyclodextrin-drug were used to predict the complexation sites. The results indicated the all the inclusion complexation between the drugs and the cyclodextrins were favourable, but do not necessary protect the potential degradation sites of the drugs. The stability results confirmed the above findings as the cyclodextrins did not enhance the stability of the drugs. Various drug-drug interaction pathways were also predicted from the experimental observations which clearly indicated the stability reductions of these drugs in combination. This leads to the conclusion that a liquid formulation combining rifampicin, isoniazid and pyrazinamide should not initiate the use of aqueous solutions as the protic ions of the solution are able to initiate the degradation of these drugs.
- Full Text:
- Authors: Chen, Yu-Jen
- Date: 2000
- Subjects: Gel permeation chromatography , Rifampin , Isoniazid , Pyridazines
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4346 , http://hdl.handle.net/10962/d1005009 , Gel permeation chromatography , Rifampin , Isoniazid , Pyridazines
- Description: Tuberculosis (TB) is a highly contagious disease caused by the bacterium known as Mycobacterium tuberculosis which is widely spread in South Africa, especially in the rural areas of the Western Province. Rifampicin, isoniazid and pyrazinamide are the three most effective drugs against this organism. However, most of the current commercial anti-TB formulations are inconvenient to administrate. This results in patient non-compliance which has increased with incomplete tuberculosis treatment and further has intensified the mortality rate. The matter is especially severe amongst the paediatric and geriatric patients. Therefore, creating a "user-friendly" but non-alcoholic liquid formulation should improve the whole situation. The key to a successful formulation relies on sufficient concentrations of the drugs within the formulation together with acceptable stability of these drugs. Therefore, during the pre-formulation stage, the solubility and stability studies of rifampicin, isoniazid and pyrazinamide are to be conducted. Rifampicin, isoniazid and pyrazinamide were fully characterized and identified by means of spectroscopic and thermal techniques. A HPLC method for simultaneous analysis of the three drugs was developed and validated. This HPLC method was employed for all the solubility and stability assessments. Unbuffered HPLC water of pH value 7.01 was chosen as the aqueous solvent. This was decided after the stability of rifampicin, isoniazid and pyrazinamide was studied at a pH range of 2 to 10. The solubility and the stability studies of rifampicin, isoniazid, pyrazinamide, rifampicin with isoniazid, rifampicin with pyrazinamide, isoniazid with pyrazinamide and rifampicin combined with both isoniazid and pyrazinamide were performed in the presence of various agents. These agents can be categorized into three groups: the surfactants (poloxamer 188, poloxamer 407 and sorbitol) which could increase the intrinsic solubility or the drugs by altering the surface tensions of the aqueous solution medium, the suspending agents (carbopol 934 and carbopol 974P) which could enable the amount of dosage required to be homogeneously suspended in the formulation without considering the low intrinsic solubility factor of the drugs, and the complexing agents (ß-cyclodextrin, hydroxypropyl-ß-cyclodextrin and -cyclodextrin) which could initiated the inclusion complex between the host cyclodextrin and the drugs, thus further enhance the solubility of the drugs . The stability assessments were performed after 7-days stability trail with the HPLC method developed. Each drug/combination of drugs were stored in closed ampoules and subjected to 25, 40 and 60° C with or without nitrogen flushing while in the presence of the above mentioned agents. While assessing the solubility/stability of the drugs in the presence of the above mentioned surfactants, the phase-solubility curves indicate that both rifampicin and pyrazinamide fail to achieve the desired concentration. Moreover, the stability-time plots clearly indicate that these surfactants fail to enhance the general stabilities of the drugs. When the stabilizing effects of the above mentioned suspending agents were investigated, it was found that although the desired concentration could be easily accomplished by suspending the drug in the aqueous carbopol solutions, the stabilities of the different drug combinations were still below the regulatory level. Cyclodextrins are well known to form inclusion complexes with less polar drug molecules. The inclusion complexation could enhance both the solubility and the stability of the included drug molecules. The computer force field generated models of the cyclodextrin-drug were used to predict the complexation sites. The results indicated the all the inclusion complexation between the drugs and the cyclodextrins were favourable, but do not necessary protect the potential degradation sites of the drugs. The stability results confirmed the above findings as the cyclodextrins did not enhance the stability of the drugs. Various drug-drug interaction pathways were also predicted from the experimental observations which clearly indicated the stability reductions of these drugs in combination. This leads to the conclusion that a liquid formulation combining rifampicin, isoniazid and pyrazinamide should not initiate the use of aqueous solutions as the protic ions of the solution are able to initiate the degradation of these drugs.
- Full Text:
Public relations in community work : a public relations programme for direct service organisations
- Carmichael-Kathan, Averil Margaret
- Authors: Carmichael-Kathan, Averil Margaret
- Date: 1992 , 2012-11-28
- Subjects: Social service -- Public relations -- Research , Community organization -- Research , Social service -- Research
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:692 , http://hdl.handle.net/10962/d1006375 , Social service -- Public relations -- Research , Community organization -- Research , Social service -- Research
- Description: The community work method of social work is a method requiring creativity, application of specialised skills and knowledge, sound planning and administration and a persuasiveness to reach the various sectors of the community in order to accomplish broad based goals. Public relations is an occupation that has a sound body of literature and theory, a code of ethics or conduct, a host of tools and methods and also requires sound planning and administration, bound together with persuasiveness to reach the various publics in order to accomplish goals affecting image, quality of service rendering and marketing of services. The present study was concerned with identifying the commonalities and the differences between the profession of community work and the occupation of public relations in order to enhance the content of community work theory for practical application by community workers. The differences between the two would, in fact, teach content to community work. It was hypothesised that public relations has a necessary function and is an occupation that can be internalised with and applied to community work for the effective marketing of organisational services. A model for incorporating public relations into community work was designed and implemented in a direct service welfare organisation with positive results. This design is applicable to other direct service welfare organisations with innovative and flexible management teams. The results of an empirical research study, making use of random sampling and questionnaires, was analysed. The results indicated that public relations and community work were comparable entities with reference to knowledge bases, values, skills, tools, methods, techniques, ethics and programmes. A third group of respondents emerged in this study - community workers practising public relations firmly within the realm of community work. This group advocated the use of marketing and communication strategies in applying the community work method effectively. The primary difference to emerge from the work research was one of emphasis in applying methods and subsequently, community work can learn a great deal from these differences which will enhance service rendering correspondingly. The culmination of this study led to several highly relevant conclusions and recommendations for welfare organisations in a Post-apartheid South Africa. The most worthwhile conclusion was that community work has a great deal to learn from public relations, and that they are combinable entities at every level. , KMBT_223
- Full Text:
- Authors: Carmichael-Kathan, Averil Margaret
- Date: 1992 , 2012-11-28
- Subjects: Social service -- Public relations -- Research , Community organization -- Research , Social service -- Research
- Language: English
- Type: Thesis , Masters , MSocSc
- Identifier: vital:692 , http://hdl.handle.net/10962/d1006375 , Social service -- Public relations -- Research , Community organization -- Research , Social service -- Research
- Description: The community work method of social work is a method requiring creativity, application of specialised skills and knowledge, sound planning and administration and a persuasiveness to reach the various sectors of the community in order to accomplish broad based goals. Public relations is an occupation that has a sound body of literature and theory, a code of ethics or conduct, a host of tools and methods and also requires sound planning and administration, bound together with persuasiveness to reach the various publics in order to accomplish goals affecting image, quality of service rendering and marketing of services. The present study was concerned with identifying the commonalities and the differences between the profession of community work and the occupation of public relations in order to enhance the content of community work theory for practical application by community workers. The differences between the two would, in fact, teach content to community work. It was hypothesised that public relations has a necessary function and is an occupation that can be internalised with and applied to community work for the effective marketing of organisational services. A model for incorporating public relations into community work was designed and implemented in a direct service welfare organisation with positive results. This design is applicable to other direct service welfare organisations with innovative and flexible management teams. The results of an empirical research study, making use of random sampling and questionnaires, was analysed. The results indicated that public relations and community work were comparable entities with reference to knowledge bases, values, skills, tools, methods, techniques, ethics and programmes. A third group of respondents emerged in this study - community workers practising public relations firmly within the realm of community work. This group advocated the use of marketing and communication strategies in applying the community work method effectively. The primary difference to emerge from the work research was one of emphasis in applying methods and subsequently, community work can learn a great deal from these differences which will enhance service rendering correspondingly. The culmination of this study led to several highly relevant conclusions and recommendations for welfare organisations in a Post-apartheid South Africa. The most worthwhile conclusion was that community work has a great deal to learn from public relations, and that they are combinable entities at every level. , KMBT_223
- Full Text:
CSP-i : an implementation of CSP
- Authors: Wrench, Karen Lee
- Date: 1987 , 2013-03-08
- Subjects: Synchronization--Computers , Programming languages (Electronic computers)
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4579 , http://hdl.handle.net/10962/d1003124 , Synchronization--Computers , Programming languages (Electronic computers)
- Description: CSP (Communicating Sequential Processes) is a notation proposed by Hoare, for expressing process communication and synchronization. Although this notation has been widely acclaimed, Hoare himself never implemented it as a computer language. He did however produce the necessary correctness proofs and subsequently the notation has been adopted (in various guises) by the designers of other concurrent languages such as Ada and occam. Only two attempts have been made at a direct and precise implementation of CSP. With closer scrutiny, even these implementations are found to deviate from the specifications expounded by Hoare, and in so doing restrict the original proposal. This thesis comprises two main sections. The first of these includes a brief look at the primitives of concurrent programming, followed by a comparative study of the existing adaptations of CSP and other message passing languages. The latter section is devoted to a description of the author's attempt at an original implementation of the notation. The result of this attempt is the creation of the CSP-i language and a suitable environment for executing CSP-i programs on an IBM PC. The CSP-i implementation is comparable with other concurrent systems presently available. In some aspects, the primitives featured in CSP-i provide the user with a more efficient and concise notation for expressing concurrent algorithms than several other message-based languages, notably occam. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Authors: Wrench, Karen Lee
- Date: 1987 , 2013-03-08
- Subjects: Synchronization--Computers , Programming languages (Electronic computers)
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4579 , http://hdl.handle.net/10962/d1003124 , Synchronization--Computers , Programming languages (Electronic computers)
- Description: CSP (Communicating Sequential Processes) is a notation proposed by Hoare, for expressing process communication and synchronization. Although this notation has been widely acclaimed, Hoare himself never implemented it as a computer language. He did however produce the necessary correctness proofs and subsequently the notation has been adopted (in various guises) by the designers of other concurrent languages such as Ada and occam. Only two attempts have been made at a direct and precise implementation of CSP. With closer scrutiny, even these implementations are found to deviate from the specifications expounded by Hoare, and in so doing restrict the original proposal. This thesis comprises two main sections. The first of these includes a brief look at the primitives of concurrent programming, followed by a comparative study of the existing adaptations of CSP and other message passing languages. The latter section is devoted to a description of the author's attempt at an original implementation of the notation. The result of this attempt is the creation of the CSP-i language and a suitable environment for executing CSP-i programs on an IBM PC. The CSP-i implementation is comparable with other concurrent systems presently available. In some aspects, the primitives featured in CSP-i provide the user with a more efficient and concise notation for expressing concurrent algorithms than several other message-based languages, notably occam. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
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