- Title
- Development of a paediatric-friendly formulation intended for the treatment of multi-drug resistant tuberculosis
- Creator
- Nkomo, Jethro
- Subject
- Drugs -- Dosage
- Subject
- Pediatrics -- Formulae, receipts, prescriptions Multidrug-resistant tuberculosis -- South Africa Primary health care -- South Africa
- Date Issued
- 2018
- Date
- 2018
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/33660
- Identifier
- vital:32962
- Description
- Children suffering from multidrug-resistant tuberculosis (MDR-TB) are treated with at least four drugs a day for at least twenty-four months. Approximately 25 000 - 32 000 children worldwide become infected with MDR-TB each year, yet there is a lack of adequate paediatric MDR-TB options for child-friendly dosage forms for the treatment of the condition. The available options are limited to manipulating different dosage forms intended for adults by means of breaking the tablets or otherwise, to deliver the drugs to children. This challenge that is faced by both health care professionals and caregivers subsequently poses drug quality, efficacy, and safety concerns to children being treated for MDR-TB. The objective of this study was to formulate a paediatric-friendly dosage form for the treatment of MDR-TB in children below the age of eight years. A fixed-dose combination (FDC) in form of a dispersible-tablet that contains two core drugs used in treatment of MDR-TB; levofloxacin and pyrazinamide, was developed. Quality by design principles was employed in developing the product. The systematic procedure ensures that quality is built into the product throughout the manufacturing process. It allows for identification of the critical quality attributes and modification of critical process parameters to lie within desired ranges. Preformulation studies were conducted on the active ingredients to investigate potential interactions and compatibility. Some of the analytical techniques employed in the process included an HPLC assay method that was developed to simultaneously separate levofloxacin and pyrazinamide, differential scanning calorimetry (DSC), infrared spectroscopy (IR), thermogravimetric analysis (TGA), and powder density studies. A direct compression tableting process was selected as the method of choice for product formulation. Active ingredients were blended with the excipients and compressed using tableting equipment to successfully produce FDC fast-disintegrating tablets containing 150 mg of levofloxacin and 300 mg pyrazinamide. The product quality was analysed and optimised using mathematical and statistical techniques such as response surface methodology (RSM) and ANOVA, to meet the required standards recommended by the United States Pharmacopoeia. The FDC dispersible tablet containing levofloxacin and pyrazinamide in the potential treatment of MDR-TB in children was successfully formulated, manufactured and evaluated. The tablet dosage form passed all the relevant quality criteria that governed the scope of this study and disintegrate in approximately 37 seconds when placed in water. It is generally a sizeable challenge to manufacture fixed-dose combination drug products due to physicochemical differences of various drugs, however, with adequate resources researchers may still find a way to formulate more child-friendly dosage forms for MDR-TB. This may lead to improved drug efficacy, reduced safety risks and decreased burden on caregivers and healthcare workers who must administer the treatment.
- Format
- xviii, 155 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Health Sciences
- Language
- English
- Rights
- Nelson Mandela University
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NMU School of Clinical Care Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | JETHRO NKOMO.pdf | 2 MB | Adobe Acrobat PDF | View Details Download |