- Title
- The development and assessment of both a separate, once-daily modified release matrix formulation of metoprolol tartrate and a combination formulation with hydrochlorothiazide
- Creator
- Arjun, Jessica
- Subject
- Metoprolol -- Controlled release
- Subject
- Chlorothiazide -- Controlled release
- Subject
- Diuretics
- Subject
- Hypertension -- Treatment
- Date Issued
- 2001
- Date
- 2001
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- vital:3742
- Identifier
- http://hdl.handle.net/10962/d1003220
- Identifier
- Metoprolol -- Controlled release
- Identifier
- Chlorothiazide -- Controlled release
- Identifier
- Diuretics
- Identifier
- 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.
- Format
- 228 p.
- Format
- Publisher
- Rhodes University
- Publisher
- Faculty of Pharmacy, Pharmacy
- Language
- English
- Rights
- Arjun, Jessica
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