The transdermal delivery route has become a popular alternative to more conventional routes, such as oral administration, but has not yet reached its full potential (Prausnitz & Langer, 2008:1261). Although the transdermal route proves to have several advantages over the conventional route, the greatest challenge is to overcome the effective barrier of the skin (Jepps et al., 2012:153). The permeation of the active pharmaceutical ingredient (API) through the skin is a complex, multi-step process and therefore predicting the permeability of the API is difficult (Jepps et al., 2012:153; Williams, 2003:30). Various approaches have been developed to overcome the skin barrier and it is recognised that the nature of the vehicle in which the API is applied plays a significant role in promoting transdermal delivery (Foldvari, 2000:417). It is important to consider the fate of the formulation ingredients and the API after application and how this changes the composition of the formulation on the skin when developing a vehicle for transdermal delivery (Lane et al., 2012:496; Otto et al., 2009:2). Wiechers (2012) proposed the Skin Delivery Gap (SDG) as an indicator for the permeability of an API. An API with a SDG < 1 will readily permeate the skin, whilst an SDG > 1 indicates a more complex delivery system is required. The partitioning of the API between the skin and the formulation is influenced by the formulation and by altering the formulation properties it is possible to manipulate the transdermal delivery of the API. The relative polarity index (RPI), based on the octanol-water partition coefficient (log P) of the stratum corneum, formulation and the API, was initially developed by Wiechers as a tool for developing formulations with an optimal polarity, to ensure the transdermal delivery of at least 50% of the API (Lane et al., 2012:498; Wiechers, 2008:94; Wiechers et al., 2004:174). The use of log P as an indicator of polarity was considered impractical by Hansen (2013) and acknowledged by both Wiechers and Abbott, who consequently developed the Formulating for Efficacy™ (FFE™) software which uses Hansen solubility parameters (HSP) instead of log P to indicate polarity (Hansen, 2013). The FFE™ calculates HSP distances, known as gaps, between the skin, API and the formulation to indicate the solubility of the different components in each other. A smaller HSP gap indicates a high solubility. The FFE™ enables the formulator to develop a formulation with a good balance between the active-formulation gap (AFG) and the skin-formulation gap (SFG) to ensure sufficient diffusion of the API into the skin. The FFE™ software was used to develop formulations containing 1.5% atropine as a model drug. Formulations of different polarity (optimised towards the stratum corneum, more hydrophilic and more lipophilic) were developed to determine the effect of the polarity of the formulation and the relevant HSP gaps on the transdermal delivery of the API. The same formulations were utilised for atropine sulphate to determine the effect the salt form has on the transdermal delivery of the API compared to the base compound. The log P and octanol-buffer partition coefficient (log D) of both atropine and atropine sulphate were determined. Log D is a more reliable indicator of distribution compared to log P, since, it considers the degree of ionisation of the API (Ashford, 2007:294). The log P and log D of atropine (0.22 and -1.26) and atropine sulphate (-1.32 and -1.23) both predicted poor skin penetration (Brown et al., 2005:177). The aqueous solubility of atropine (0.9 mg/ml) also predicted limited transdermal delivery, while the solubility of atropine in phosphate buffer solution (PBS pH 7.4) (5.8 mg/ml) indicated favourable permeation (Naik et al., 2000:321). The high degree of ionisation of the API (99.68 %), at pH 7.4, predicts only a small amount will penetrate the skin (Barry, 2007:576). The membrane release study confirmed the API was released from the different formulations and subsequently skin diffusion studies were conducted, followed by tape stripping after 12 h, to determine which formulation resulted in the highest transdermal delivery of the API. The atropine hydrophilic formulation released the highest percentage of API after 6 h (13.930%). This was explained by the low affinity the lipophilic atropine has towards the hydrophilic formulation (Otto et al., 2009:9). The highest percentage transdermal delivery (0.065%) was observed with the lipophilic formulation containing atropine. The higher SFG compared to the AFG of the lipophilic formulation initially predicted poor transdermal delivery, but when considering the HSP profile and molar volume of the different ingredients, it was observed the dimethyl isosorbide (DMI) penetrated and provided a desirable environment for the API in the skin. The residual formulation (containing less DMI and more polyethylene glycol 400 (PEG 8) and liquid paraffin) was less desirable for the API and was therefore forced out of the formulation (Abbott, 2012:219). Both these factors contributed to the high transdermal delivery of atropine from the lipophilic formulation. The atropine sulphate hydrophilic formulation had the highest percentage in the stratum corneum-epidermis (0.29 μg/ml) and the hydrophilic formulation of both atropine and atropine sulphate had the highest concentration in the epidermis-dermis (both 0.55 μg/ml). The hydrophilic formulations had the lowest driving force provided by the AFG and the only driving force for the API to leave the formulation was the concentration gradient. These formulations had the lowest transdermal delivery which indicates the API had not fully traversed through the skin after 12 h. According to Wiechers, a minimised SFG would indicate the formulation is optimised towards the stratum corneum and should essentially deliver the highest percentage of API through the skin. The results obtained are contrary to this belief and it is concluded that the total HSP profile and the molar volume of the formulation and the API should be considered when developing a formulation with optimal transdermal delivery rather than just the SFG. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The transdermal delivery route has become a popular alternative to more conventional routes, such as oral administration, but has not yet reached its full potential (Prausnitz & Langer, 2008:1261). Although the transdermal route proves to have several advantages over the conventional route, the greatest challenge is to overcome the effective barrier of the skin (Jepps et al., 2012:153). The permeation of the active pharmaceutical ingredient (API) through the skin is a complex, multi-step process and therefore predicting the permeability of the API is difficult (Jepps et al., 2012:153; Williams, 2003:30). Various approaches have been developed to overcome the skin barrier and it is recognised that the nature of the vehicle in which the API is applied plays a significant role in promoting transdermal delivery (Foldvari, 2000:417). It is important to consider the fate of the formulation ingredients and the API after application and how this changes the composition of the formulation on the skin when developing a vehicle for transdermal delivery (Lane et al., 2012:496; Otto et al., 2009:2). Wiechers (2012) proposed the Skin Delivery Gap (SDG) as an indicator for the permeability of an API. An API with a SDG < 1 will readily permeate the skin, whilst an SDG > 1 indicates a more complex delivery system is required. The partitioning of the API between the skin and the formulation is influenced by the formulation and by altering the formulation properties it is possible to manipulate the transdermal delivery of the API. The relative polarity index (RPI), based on the octanol-water partition coefficient (log P) of the stratum corneum, formulation and the API, was initially developed by Wiechers as a tool for developing formulations with an optimal polarity, to ensure the transdermal delivery of at least 50% of the API (Lane et al., 2012:498; Wiechers, 2008:94; Wiechers et al., 2004:174). The use of log P as an indicator of polarity was considered impractical by Hansen (2013) and acknowledged by both Wiechers and Abbott, who consequently developed the Formulating for Efficacy™ (FFE™) software which uses Hansen solubility parameters (HSP) instead of log P to indicate polarity (Hansen, 2013). The FFE™ calculates HSP distances, known as gaps, between the skin, API and the formulation to indicate the solubility of the different components in each other. A smaller HSP gap indicates a high solubility. The FFE™ enables the formulator to develop a formulation with a good balance between the active-formulation gap (AFG) and the skin-formulation gap (SFG) to ensure sufficient diffusion of the API into the skin. The FFE™ software was used to develop formulations containing 1.5% atropine as a model drug. Formulations of different polarity (optimised towards the stratum corneum, more hydrophilic and more lipophilic) were developed to determine the effect of the polarity of the formulation and the relevant HSP gaps on the transdermal delivery of the API. The same formulations were utilised for atropine sulphate to determine the effect the salt form has on the transdermal delivery of the API compared to the base compound. The log P and octanol-buffer partition coefficient (log D) of both atropine and atropine sulphate were determined. Log D is a more reliable indicator of distribution compared to log P, since, it considers the degree of ionisation of the API (Ashford, 2007:294). The log P and log D of atropine (0.22 and -1.26) and atropine sulphate (-1.32 and -1.23) both predicted poor skin penetration (Brown et al., 2005:177). The aqueous solubility of atropine (0.9 mg/ml) also predicted limited transdermal delivery, while the solubility of atropine in phosphate buffer solution (PBS pH 7.4) (5.8 mg/ml) indicated favourable permeation (Naik et al., 2000:321). The high degree of ionisation of the API (99.68 %), at pH 7.4, predicts only a small amount will penetrate the skin (Barry, 2007:576). The membrane release study confirmed the API was released from the different formulations and subsequently skin diffusion studies were conducted, followed by tape stripping after 12 h, to determine which formulation resulted in the highest transdermal delivery of the API. The atropine hydrophilic formulation released the highest percentage of API after 6 h (13.930%). This was explained by the low affinity the lipophilic atropine has towards the hydrophilic formulation (Otto et al., 2009:9). The highest percentage transdermal delivery (0.065%) was observed with the lipophilic formulation containing atropine. The higher SFG compared to the AFG of the lipophilic formulation initially predicted poor transdermal delivery, but when considering the HSP profile and molar volume of the different ingredients, it was observed the dimethyl isosorbide (DMI) penetrated and provided a desirable environment for the API in the skin. The residual formulation (containing less DMI and more polyethylene glycol 400 (PEG 8) and liquid paraffin) was less desirable for the API and was therefore forced out of the formulation (Abbott, 2012:219). Both these factors contributed to the high transdermal delivery of atropine from the lipophilic formulation. The atropine sulphate hydrophilic formulation had the highest percentage in the stratum corneum-epidermis (0.29 μg/ml) and the hydrophilic formulation of both atropine and atropine sulphate had the highest concentration in the epidermis-dermis (both 0.55 μg/ml). The hydrophilic formulations had the lowest driving force provided by the AFG and the only driving force for the API to leave the formulation was the concentration gradient. These formulations had the lowest transdermal delivery which indicates the API had not fully traversed through the skin after 12 h. According to Wiechers, a minimised SFG would indicate the formulation is optimised towards the stratum corneum and should essentially deliver the highest percentage of API through the skin. The results obtained are contrary to this belief and it is concluded that the total HSP profile and the molar volume of the formulation and the API should be considered when developing a formulation with optimal transdermal delivery rather than just the SFG. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The study explores the role that the CEO plays in the facilitation of the Strategic Management Process (SMP) within the small and medium sized companies on the JSE with a turnover between R10 to R80 mil. In answering the question “Is the facilitation of the SMP vested in the CEO alone or does he/she share the overall responsibility with Executives, Functional Managers, Supervisors or Consultants? In response to this question the findings purport that the majority view (69%) strengthen the CEO’s influential role in the facilitation of the SMP. This was evident within the launching and growth phase of the company, where the owner plays a big role as the visionary and as there is no formal distinction between the facilitation and the SMP. In contrast, we have to acknowledge the minority view (31%) of CEO’s who engages Executives, Functional Managers, Supervisors, Consultants and other selected personnel in strategic discussions, in ways to leverage their perspective and insights and create shared meaning and ownership. This could be used to develop skills in facilitation, reaffirm team norms and develop agility to respond timeously and strategically to rapid change. This bridges the transition from the higher growth phase and lower maturity phase of the company. For that reason this will enhance decision making, creativity, collaboration, enumerate core values and stimulate growth within the company.

The objectives of this study are to investigate the formulation and implementation of strategies within Retail Bank at corporate, business unit, functional and operational levels, focusing specifically on who is accountable and responsible for strategy formulation and implementation at each of these levels, as well as the factors related to the success or failure of strategy implementation and how success is measured. In addition, this study attempts to determine whether or not the financial industry as a whole plays a significant role in the success of strategy implementation within Retail Bank.

The ability to formulate monoclonal antibodies at high concentration in a low-viscosity form is of broad interest in drug delivery, as monoclonal antibody-based drugs are now prescribed for cancer, autoimmune disorders, and many other diseases. Herein, we create highly concentrated antibody dispersions (up to 260 mg/mL) via three different methods, utilizing proline as an interacting depletant or trehalose as a non-interacting depletant. These dispersions are able to achieve viscosities an order of magnitude lower than similarly concentrated antibody solutions over a range of formulation pHs. When diluted, these antibody dispersions return to monomer. The proline acts to minimize protein zeta potential, thus reducing the electrostatic repulsion on the protein, even when formulated 3 pH units away from the antibody pI. In addition, it acts as a depletant, forcing the monomers into cluster via osmotic effects / text

In this work, a model microbial agent for bioremediation was improved using fermentation and formulation methods. The outcomes of the fermentation work include the development of a new culture medium which increased the cell productivity greater than one order of magnitude. A robust functionality to degrade the herbicide atrazine was expressed. The new medium was scaled-up to a 2L bioreactor. Liquid bacterial culture was not inherently stable and lost viability at both 4°C and 25°C storage. When liquid bacterial culture was formulated by encapsulation in a biopolymer gel and applied to zeolite the transfer of cells from bacterial culture to formulated carrier was highly efficient. No loss of viability was measured from the immobilization process, and the functionality of the agent was retained. The formulated agent expressed an extended shelf life of at least 10 weeks when stored in ambient (25°C) temperature. When the formulation granules were inoculated into sterile soil, viability of the granules was stable and also retained the maximum level of functionality for the full test period of 10 weeks. The soil surrounding the formulation granules was also enumerated. The number of cells in the soil increased after a single inoculation of the formulation and the maximum level of functionality was conveyed from the formulation to the surrounding soil. The formulated inoculant constitutes an improvement for a bioremediation strain to stabilize the agent, produce an extended shelf life at ambient temperatures, and maintain the functionality of a microbe to utilize atrazine. In this thesis we have used a biopolymer formulation in which an inoculum is simply mixed into a gel and applied directly to the surface of the zeolite with no special equipment, drying, temperatures, or secondary re-growth steps required. It is a simple model system consisting of a carrier, and a artificial biofilm. As a technique to produce stable functional inoculants for bioremediation, the work presented here demonstrates an approach that is simple, practical, effective, and robust.

Oral drug administration remains the most popular route of drug delivery. Absorption of the dissolved drug through the intestinal epithelial membrane is a prerequisite to systemic bioavailability and drug efficacy. In efforts to reduce the long lead times, attrition rates, and costs of drug discovery and development, computational models have been developed to predict the membrane permeability and absorption efficiency of a dosed drug. Many models utilize various molecular descriptors to correlate with in vitro permeability or human intestinal absorption data. It is widely accepted that the two most significant physicochemical properties that control a compound's passive transport process are its aqueous solubility and lipophilicity characteristics.This work will discuss the theoretical background of passive transport, a number of computational models developed to predict in vitro permeability, other models that predict human fraction of dose absorbed, and predicting absorption efficiency relative to a maximum dose. A newly developed prediction method is also presented, that reveals an interesting relationship between fraction absorbed and the melting point of the drug.

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This dissertation addresses the problem of adaptive image filtering. Although the topic has a long history in the image processing community, researchers continuously present novel methods to obtain ever better image restoration results. With an expanding market for individuals who wish to share their everyday life on social media, imaging techniques such as compact cameras and smart phones are important factors. Naturally, every producer of imaging equipment desires to exploit cheap camera components while supplying high quality images. One step in this pipeline is to use sophisticated imaging software including, e.g., noise reduction to reduce manufacturing costs, while maintaining image quality. This thesis is based on traditional formulations such as isotropic and tensor-based anisotropic diffusion for image denoising. The difference from main-stream denoising methods is that this thesis explores the effects of introducing contextual information as prior knowledge for image denoising into the filtering schemes. To achieve this, the adaptive filtering theory is formulated from an energy minimization standpoint. The core contributions of this work is the introduction of a novel tensor-based functional which unifies and generalises standard diffusion methods. Additionally, the explicit Euler-Lagrange equation is derived which, if solved, yield the stationary point for the minimization problem. Several aspects of the functional are presented in detail which include, but are not limited to, tensor symmetry constraints and convexity. Also, the classical problem of finding a variational formulation to a given tensor-based partial differential equation is studied. The presented framework is applied in problem formulation that includes non-linear domain transformation, e.g., visualization of medical images. Additionally, the framework is also used to exploit locally estimated probability density functions or the channel representation to drive the filtering process. Furthermore, one of the first truly tensor-based formulations of total variation is presented. The key to the formulation is the gradient energy tensor, which does not require spatial regularization of its tensor components. It is shown empirically in several computer vision applications, such as corner detection and optical flow, that the gradient energy tensor is a viable replacement for the commonly used structure tensor. Moreover, the gradient energy tensor is used in the traditional tensor-based anisotropic diffusion scheme. This approach results in significant improvements in computational speed when the scheme is implemented on a graphical processing unit compared to using the commonly used structure tensor. / VIDI / NACIP / GARNICS / EMC^2

The objectives of this study are to investigate the formulation and implementation of strategies within Retail Bank at corporate, business unit, functional and operational levels, focusing specifically on who is accountable and responsible for strategy formulation and implementation at each of these levels, as well as the factors related to the success or failure of strategy implementation and how success is measured. In addition, this study attempts to determine whether or not the financial industry as a whole plays a significant role in the success of strategy implementation within Retail Bank.