Statistical optimisation of a terbinafine-containing cream
- Authors: Strydom, Lana
- Date: 2019
- Subjects: Chemicals -- Physiological effect , Pharmaceutical chemistry Medical microbiology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/44067 , vital:37101
- Description: Terbinafine hydrochloride (TBH) belongs to the allylamine class of antifungals and displays a favourable dermatopharmacokinetic profile, being both lipophilic and keratinophilic. It has thus been included in a variety of topical dosage forms for the treatment of dermatomycoses, many of which have been the subject of optimisation studies, with the purpose of improving the product. Since a TBH-containing cream had not been found in literature to have been optimised before, the aim of this study was to optimise a TBH cream formulation. A TBH cream formulation, suitable for optimisation, was developed. Preformulation tests were undertaken, including active-excipient compatibility testing using a combined thermal method consisting of both differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), as well as isothermal stress testing (IST). With the confirmation of the suitability of the selected excipients, development of a suitable TBH cream took place largely by a trial-and-error approach. The choice of a suitable formulation was made based on the physical appearance and viscosity of the cream, for which a viscosity specification was set. The identified TBH cream formulation was evaluated for its physical appearance and physicochemical aspects to confirm its appropriateness for the purpose of further optimisation. Based on literature and observations from the preformulation and formulation stage, factors and responses for study during the optimisation stage were identified to study using a circumscribed central composite design (CCCD) at five levels (-1.612, -1, 0, +1, +1.612). Total percentage of surfactant (TPS), homogenisation speed (HS) and cooling rate (CR), were selected as factors to study their influence on cream viscosity, in vitro TBH release from the cream, as well as the chemical stability of TBH within the cream formulation. Following the application of stepwise multiple linear regression to the mathematical models, a suitable prediction model was only obtained for one response, cream viscosity at a shear rate of 20 s-1. A linear model was also found to fit the data for % in vitro TBH release after one hour, although a low R2 of 0.497 made the model unsuitable for prediction purposes. No mathematical model could be fit to the results for the response assessing the change in TBH concentration following seven days’ storage at accelerated stability conditions. The determination of the optimum TBH cream formulation was made chiefly on the basis of the results for cream viscosity and the optimised formulation was identified to have a predicted viscosity of 8.33 Pa.s and the factor settings to obtain this cream were a CR of 1.3 °C/min, HS set at 3400 rpm, and TPS of 4.2 %. Validation of the optimised TBH cream formulation was performed for cream viscosity at a shear rate of 20 s-1 and revealed that there was good agreement between the measured and predicted viscosity values. The optimised TBH cream underwent rheological characterisation and was compared to the innovator, Lamisil® cream, with both creams found to meet the desirable rheological profile. In vitro release testing (IVRT) was used to compare the release of TBH from the optimised TBH cream and Lamisil® cream, and the optimised TBH cream was found to show much greater TBH release over a six-hour time period than Lamisil® cream. Stability testing of the optimised TBH cream took place at accelerated stability testing conditions of 40 °C ± 2 °C and 75 ± 5 % relative humidity (RH). To assay the formulation and determine content uniformity over the three-month storage period, a suitable stability-indicating reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated. Other cream properties which were tested included: qualitative aspects, viscosity, pH and microbial limits. At the end of the three-month stability testing period, the cream was found to meet most of the specifications set, except for cream homogeneity and viscosity. A TBH cream formulation was thus developed and optimised to meet a certain viscosity specification. Although this formulation was found to meet the viscosity specification on the day after its manufacture, the viscosity was found to increase on storage, such that it was outside the set viscosity specification range.
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- Date Issued: 2019
Pilates for postural stability in computer users
- Authors: Strydom, Lana
- Date: 2008
- Subjects: Pilates method , Human beings -- Attitude and movement
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:10094 , http://hdl.handle.net/10948/867 , Pilates method , Human beings -- Attitude and movement
- Description: The impact of computer use is evident in every day life (Harrington, Carter, Birrell and Gompertz, 2000:264). Lind (2002:18) explains that global trends continue to show that the most severe work-related health problems that exist amongst computer users are musculoskeletal disorders. As technology has lead to increases in automation, so it has lead to increases in work-related illnesses. Although studies have explored the effects of ergonomics (Thibodeau, 1995:322) in static working positions there has been little evidence supporting a solution in overcoming poor occupational postures. Many health practitioners argue that occupationally caused, or aggravated, musculoskeletal disorders are steadily increasing. Thus, even though computers have improved productivity and made work easier for the population in general, they have adverse effects as well. Designing the proper tools or a setup of the work place is of prime importance for the elimination of chronic diseases attributed to sedentary lifestyles. Regular physical activity had long been regarded as an important component of a healthy lifestyle. This notion has recently been reinforced by scientific evidence linking regular physical activity with a wide array of physical and mental health benefits, synonymous with an improvement in wellness (Pratt, Macera, and Wang, 2000:63). According to Pratt et al. (2000:63) higher direct medical costs associates with physical inactivity. Further cross-sectional epidemiologic studies and controlled experimental investigations conducted by Okura, Nakata and Tanaka (2003:1131) had demonstrated that physically active adults, in contrast to their sedentary counterparts, tend to develop and maintain higher levels of physical fitness. These studies had not only demonstrated the positive results of physical activity, such as an improvement in blood lipid profile, body composition, glucose tolerance and insulin sensitivity, but had also shown that participation in such activity decreased the risk of developing several chronic hypokinetic diseases, including coronary heart disease (CHD), hypertension, non-insulin dependant diabetes mellitus (type II), osteoporosis, colon cancer, anxiety and depression. In addition, low levels of habitual physical activity and the subsequent low levels of physical fitness were associated with a marked increase in all-cause mortality rates. Okura et al. (2003:1131) confirm that effects of exercise intensity on physical fitness and risk factors for coronary Herat disease.
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- Date Issued: 2008