Application of quality by design to the manufacture of a multiparticulate prednisone dosage form
- Authors: Manda, Arthur
- Date: 2020-04
- Subjects: Drugs -- Quality control , Drugs -- Design -- Quality control , Drugs -- Dosage forms , Drug development -- Quality control , Pharmaceutical industry -- Quality control , Prednisone , High throughput screening (Drug development)
- Language: English
- Type: text , Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/117986 , vital:34583
- Description: For many years, quality by testing was the only approach to guarantee quality of drug products before the Food and Drug Administration launched the concept of current Good Manufacturing Practice. In order to gain more knowledge of the manufacturing process, a new system known as Quality by Design was introduced into the pharmaceutical industry. Quality by Design is based on thorough understanding of how materials, process parameters and interaction thereof impact final product quality. Quality by Design is a systematic approach to product development which ensures that quality is built into a product during product development and not just tested into it. The aim of Quality by Design is to achieve optimum product quality with consistent dosage form performance and minimal risk of failure in patients. The objective of these studies was to implement a Quality by Design approach to establish a design space for the development and manufacture of a safe, effective and stable multi-partite solid oral dosage form for prednisone as an alternative to currently marketed prednisone formulations. Multi-particulate dosage forms offer significant advantages over conventional technologies. In addition to lowering the incidence of gastrointestinal irritation they exhibit a reduced risk of dose dumping and a large surface area which favours dissolution. Furthermore, their free flowing nature facilitates reproducible capsule filling and consequently uniformity of dosing. Different multi-particulate dosage forms exist however a multiple-unit pellet system was investigated during these studies. Quality by Design principles were used to develop and establish a reversed-phase high performance liquid chromatographic method for quantifying prednisone from solid oral dosage forms. A Central Composite Design was used to generate multivariate experiments and to investigate the impact of input variables on the quality and performance of the analytical method. The optimized method was validated according to International Council for Harmonization guidelines and was found to be linear, precise, accurate and specific for the quantitation of prednisone. Pre-formulation studies were conducted and included the assessment of particle size, particle shape, powder flow properties and compatibility studies. Carr’s index, Hausner ratio and the Angle of Repose were used to evaluate powder flow properties and results generated from all studies suggest the need for adding a glidant and lubricant to improve pellet flow. The images generated from Scanning Electron Microscopy were used to analyze particle shape and size. Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were used to evaluate API-excipient compatibility. All excipients investigated were found to be compatible with prednisone and suitable for formulation development studies. Extrusion-spheronization was used to manufacture prednisone pellets. Extrusion-spheronization is a multi-step process involving many factors. Quality risk management tools particularly an Ishikawa Fishbone (cause and effect) diagram and failure mode and effects analysis were used to narrow down potentially significant factors to a reasonable number that could be investigated experimentally. Risk priority numbers were used to quantify risk and factors above a set threshold value were considered to be of high risk. A total of eleven risk factors were identified as high. A Plackett-Burman study was conducted to narrow down the eleven high risk factors to identify the most impactful factors viz., microcrystalline cellulose content, sodium starch glycolate content, extrusion speed and spheronization time. Evaluation of four factors was carried over to optimization studies using a Box-Behnken Design and following identifaction of the optimum process settings and excipient content a design space for the manufacture of a multi-partite dosage form containing prednisone was established.
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Effects of organic and inorganic pollutants on the quality of river water and evaluation of possible negative effects on human health in the Eastern Cape Province
- Authors: Vumazonke, Sesethu
- Date: 2020-04
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/164727 , vital:41158
- Description: Thesis (MSc)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
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Development and assessment of a fixed dose combination of perindopril arginine and indapamide loaded microparticles
- Authors: Mandava, Tavonga Tyomai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164413 , vital:41116
- Description: Thesis (MSc)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
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Development and assessment of a smart thermosetting intranasal hydrogel for lamotrigine
- Authors: Melamane, Siyabonga
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62975 , vital:28349
- Description: Expected release date-April 2020
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Development and assessment of gastroretentive sustained release captopril micro-balloons
- Authors: Oridota, Omoyosola Omolola
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63491 , vital:28419
- Description: Expected release date-April 2020
- Full Text:
Formulation, characterisation and optimisation of self-nanoemulsifying drug delivery systems (SNEDDS) loaded with artemether and lumefantrine
- Authors: Mudyahoto, Tsitsi
- Date: 2018
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63503 , vital:28422
- Description: Expected release date-April 2020
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The development, manufacture and assessment of solid dispersions of gliclazide
- Authors: Govere, Grace Shalom
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/63390 , vital:28405
- Description: Expected release date-April 2020
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The development, manufacture and evaluation of a selfmicro-emulsifying drug delivery system for efavirenz
- Authors: Musakana, Tanyaradzwa Gracious
- Date: 2018
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/62643 , vital:28223
- Description: Expected release date-April 2020
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Preparation and evaluation of captopril - ion exchange resin complexes
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59146 , vital:27441
- Description: Restricted access-thesis embargoed for 2 years
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Taste masking of clarithromycin with ion exchange resins
- Authors: Ntemi, Pascal Vitalis
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65178 , vital:28701
- Description: Expected release date-May 2019
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Development and assessment of sustained release stavudine loaded microparticles
- Authors: Zindove, Chiedza Cathrine
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54722 , vital:26603
- Description:
Stavudine (D4T) has been used as first line treatment for HIV/AIDS and is part of highly active anti retroviral treatment (HAART). It is an affordable medicine and its use is beneficial in resource limited settings. However D4T exhibits dose dependent side effects that may lead to non-adherence in patients. This study was undertaken to formulate, develop and manufacture a dosage form that could reduce dose dependent side effects by decreasing the dose of D4T but still exhibit antiretroviral (ARV) activity. The use of sustained release (SR) formulations of D4T that ensure constant levels of the D4T in the body would not only optimize therapy but also reduce the incidence of side effects thereby increasing patient adherence. SR microparticles containing 30mg D4T were manufactured and loaded into size 3 hard gelatine capsules prior to analysis. The D4T microparticles were manufactured by microencapsulation using non-aqueous oil-in-oil solvent evaporation approach. D4T-excipient, excipient-excipient interactions and D4T purity were assessed using Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Copolymers synthesized from acrylic and methacrylic acid esters viz., Eudragit® RSPO and S100 were used as rate retardant materials and the effect of microcrystalline cellulose (Avicel® PH102) on the microparticles was also investigated. Magnesium stearate was used as a droplet stabilizer and n-hexane was added to harden the microspheres formed in a liquid paraffin continuous phase. The microparticles were optimized using a Box Behnken design and Response Surface Methodology (RSM). The microparticles were characterized in terms of their flow properties and encapsulation efficiency (% EE), in addition to visualization of the surface morphology with Scanning Electron Microscopy. In vitro D4T release studies were performed using USP Apparatus III in media of different pH and the samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection that had been developed and optimized using a Central Composite Design (CCD). The method was validated according to ICH guidelines. The IR spectra and DSC thermographs revealed that D4T exhibited thermal stability and there was no evidence of D4T-excipient and excipient-excipient interactions. The microparticles that were produced were white, free flowing and were obtained in a high yield with high encapsulation efficiency. Scanning Electron Microscopy studies revealed that the microparticles were spherical and porous in nature. In vitro D4T release extended to 12 hours and the mechanism of release was established using model dependent methods by fitting the data to a Zero order, First order, Higuchi and Hixson Crowell model. It was observed that the mechanism of D4T release was diffusion-controlled and that the data was best fitted to the Higuchi model with correlation coefficients > 0.9. The release mechanism was confirmed using the Korsmeyer-Peppas model that revealed that most of the formulations exhibited anomalous transport kinetics with the release exponent, n, ranging from 0.5
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