Please read the abstract in the section 00front of this document / Dissertation (MSc(Consumer Science))--University of Pretoria, 2005. / Consumer Science / unrestricted

Alkali compounds were added to a South African coal with a high swelling propensity and the behaviour of the blends were investigated. A vitrinite-rich bituminous coal from the Tshikondeni coal mine in the Limpopo province of South Africa was used. To reduce the influence of the minerals in the coal, the coal was partially demineralized by leaching with HCl and HF. The ash content of the coal sample was successfully reduced from 17.7% to 0.6%. KOH, KCl, K2CO3 and KCH3CO2 were then added to the demineralized coal in mass percentages of 1%, 4%, 5% and 10%. The free swelling indices (FSI) of the blends were determined and the samples were subjected to acquisition of TMA and TG-MS data. Addition of these potassium compounds to the demineralized coal reduced the swelling of the vitrinite-rich coal. From the free swelling indices of the various mixtures, it was concluded that the potassium compounds reduce the swelling of the coal in the following order of decreasing impact: KCH3CO2 > KOH > K2CO3 > KCl. From dilatometry experiments done on the blends with the 10% addition of potassium compounds, it was seen that with the addition of potassium compounds to the demineralized coal, a reduction in dilatation volume was obtained. The influence of the potassium compound in decreasing order: K2CO3> KOH> KCH3CO2> KCl. An increase in the softening temperature was observed for the demineralized coal-alkali blends. Thermogravimetric analyses were performed on the demineralized coal-potassium blended samples (<75 μm). These samples were pyrolyzed under a nitrogen atmosphere to a maximum temperature of 1200 °C using a heating rate of 10 °C/min. The relative reactivity for each of the blends with the different wt% addition was determined. From these results it was seen that KCH3CO2 increased the relative reactivity, whereas the KOH, KCl and K2CO3 showed an inhibiting influence. The attached mass spectrometer provided information on the low molecular mass gaseous products formed in the various temperature ranges as the thermal treatment proceeded. From the mass spectroscopy results, it was found that the potassium compounds decreased the temperature at which maximum evolution of H2 takes place. Thermomechanical analyses were performed on the 10 wt% addition of the potassium compounds to the demineralized coal. During TMA analyses, the sample was heated to 1000 °C using a heating rate of 10 °C/min. From the TMA result obtained it was clear that the addition of KCl did not have an influence on the swelling of the demineralized coal. All results are discussed. / MSc (Chemistry), North-West University, Potchefstroom Campus, 2014

A pharmaceutical dosage form is an entity that is administered to patients so that they receive an effective dose of an active pharmaceutical ingredient (API). The proper design and formulation of a transdermal dosage form require a thorough understanding of the physiological factors affecting percutaneous penetration and physicochemical characteristics of the API, as well as that of the pharmaceutical exipients that are used during formulation. The API and pharmaceutical excipients must be compatible with one another to produce a formulation that is stable, efficacious, attractive, easy to administer, and safe (Mahato, 2007:11). Amongst others, the physicochemical properties indicate the suitability of the type of dosage form, as well as any potential problems associated with instability, poor permeation and the target site to be reached (Wells & Aulton, 2002:337). Therefore, when developing new or improved dosage forms, it is of utmost importance to evaluate the factors influencing design and formulation to provide the best possible dosage form and formulation for the API in question. Delivery of an API through the skin has long been a promising concept due to its large surface area, ease of access, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the therapy. This is true whether a local or systemic pharmacological effect is desired (Aukunuru et al., 2007:856). However, most APIs are administered orally as this route is considered to be the simplest, most convenient and safest route of API administration. Since ibuprofen is highly metabolised in the liver and gastrointestinal tract, oral administration thereof results in decreased bioavailability. Furthermore, it also causes gastric mucosal damage, bleeding and ulceration. Another obstacle associated with oral API delivery is that some APIs require continuous delivery which is difficult to achieve (Bouwstra et al., 2003:3). Therefore, there is significant interest to develop topical dosage forms for ibuprofen to avoid side effects associated with oral delivery and to provide relatively consistent API levels at the application site for prolonged periods (Rhee et al., 2003:14). The aim of this study was to determine the influence of selected formulation factors on the transdermal delivery of ibuprofen. In order to achieve this aim, the physicochemical properties of ibuprofen had to be evaluated. The aqueous solubility, pH-solubility profile, octanol-water partition coefficient (log P-value) and octanol-buffer distribution coefficient (log D-values, pH 5 and 7.4) of ibuprofen were determined. According to Naik et al., (2000:319) the ideal aqueous solubility of APIs for transdermal delivery should be more than 1 mg.ml-1. However, results showed that ibuprofen depicted an aqueous solubility of 0.096 mg.ml-1 ± 25.483, which indicated poor water solubility and would therefore be rendered less favourable for transdermal delivery if only considering the aqueous solubility. The pH-solubility profile depicted that ibuprofen was less soluble at low pH-values and more soluble at higher pH-values. Previous research indicated that the ideal log Pvalues for transdermal API permeation of non steroid anti-inflammatory drugs (NSAIDs) are between 2 and 3 (Swart et al., 2005:72). Results obtained during this study indicated a log P-value of 4.238 for ibuprofen. This value was not included in the ideal range, which is an indication that the lipophilic/hydrophilic properties are not ideal, and this might therefore; contribute to poor ibuprofen penetration through the skin. Furthermore, the obtained log D-values at pH 5 and 7.4 were 3.105 and 0.386, respectively. Therefore, it would be expected that ibuprofen incorporated into a formulation prepared at a pH of 5 would more readily permeate the skin compared to ibuprofen incorporated into a formulation prepared at a pH of 7.4. A gel, an emulgel and a Pheroid™ emulgel were formulated at pH 5 and 7.4, in order to examine which dosage form formulated at which pH would deliver enhanced transdermal delivery. Obtained diffusion results of the different semi-solid formulations were furthermore compared to a South African marketed commercial product (Nurofen® gel) in order to establish if a comparable formulation could be obtained. An artificial membrane was used to conduct the membrane permeation studies over a period of 6 h, in order to determine whether ibuprofen was in fact released from the formulations through the membrane. Skin permeation studies were conducted using Franz diffusion cells over a period of 12 h where samples were withdrawn at specified time intervals. All the formulations exhibited an increase in the average cumulative amount of ibuprofen released from the formulations and that permeated the membrane when compared to Nurofen® gel. This increase was statistically significant (p<0.05) for the gel, emulgel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest cumulative amount of ibuprofen that permeated the membrane. Preparations formulated at a pH of 5, did not differ significantly from Nurofen® when the average cumulative amount of ibuprofen that permeated the membrane were compared. The following rank order for the average cumulative amount released from the formulations could be established: Gel (pH 7.4) >>>> Pheroid™ emulgel (pH 7.4) > Emulgel (pH 7.4) >>> Gel (pH 5)> Pheroid™ emulgel (pH 5) ≈ Emulgel (pH 5) > Nurofen® gel. On the other hand, all the formulations exhibited an increase in the average cumulative amount of ibuprofen that permeated the skin when compared to Nurofen® gel. This increase was statistically significant (p < 0.05) for the gel, emulgel and Pheroid™ emulgel at pH 5, as well as the emulgel and Pheroid™ emulgel at pH 7.4. The emulgel at pH 5 exhibited the highest cumulative amount of ibuprofen that permeated the skin. The following rank order for the average cumulative amount released from the formulations and that permeated the skin could be established: Emulgel (pH 5) >> Pheroid™ emulgel (pH 5) > Gel (pH 5) > Emulgel (pH 7.4)> Pheroid™ emulgel (pH 7.4) ≈ Emulgel (pH 7.4) >> Nurofen® gel > Gel (pH 7.4). From this rank order it was clear that a trend was followed where the pH of formulation also played a role in ibuprofen permeation. All the formulations exhibited a higher release rate and flux when compared to Nurofen® gel. This was statistically significant for the emulgel, gel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest release rate and flux. This was observed for the membrane and skin permeation studies. All the formulations (including Nurofen® gel) presented a correlation coefficient (r2) of 0.972 – 0.995 for membrane permeation studies, and 0.950 – 0.978 for skin permeation studies; indicating that the release of ibuprofen from each of the formulations could be described by the Higuchi model. Furthermore, all the formulations exhibited a prolonged lag time compared to Nurofen® gel which indicated that the ibuprofen was retained for a longer time by the base. This was statistically significant (p < 0.05) for the emulgel at pH 7.4, the gel and Pheroid™ emulgel at pH 5. The gel at pH 7.4 exhibited a lag time closest to that of Nurofen® gel and this difference could not be classified as statistically significant (p > 0.286). This was observed for the membrane and skin permeation studies. Nurofen® gel exhibited the highest ibuprofen concentration in the stratum corneum as well as in the epidermis followed by the gel at pH 7.4. However, results obtained for all the formulations indicated that topical as well as transdermal delivery of ibuprofen was achieved. The pH of a formulation plays an important role with respect to API permeation. Ibuprofen is reported to have a pKa value 4.4 (Dollery, 1999:I1); and by application of the Henderson-Hasselbach equation, at pH 5, 20.08% of ibuprofen will be present in its unionised form and at pH 7.4, 0.1% ibuprofen will exist in its unionised form. Since the unionised form of APIs is more lipid soluble than the ionised form, unionised forms of APIs permeate more readily across the lipid membranes (Surber & Smith, 2000:27). Therefore, it would be expected that ibuprofen formulated at pH 5 would be more permeable than formulations at pH 7.4. However, this did not correspond to the results (membrane studies) obtained in this study. It may be attributed to the solubility of ibuprofen in the different formulations. According to the pH-solubility profile of ibuprofen obtained in this study, it was more soluble at pH 7.4 than at pH 5. This was due to the fact that ibuprofen is a weak acidic compound, and for every 3 units away from the pKa-value, the solubility changes 10-fold (Mahato, 2007:14). However, with regard to the skin permeation studies, enhanced permeation was obtained with the formulations prepared at pH 5. This was in accordance with Corrigan et al., (2003:148) who stated that NSAIDs are less soluble and more permeable at low pH values, and more soluble and less permeable at high pH values. This was most probably due to the fact that unionised species, although possessing a lower aqueous solubility than the ionised species, resulted in enhanced skin permeation due to being more lipid-soluble. Finally, stability tests on the different semi-solid formulations for a period of three months at different temperature and humidity conditions were conducted to determine product stability. The formulations were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. Stability tests included: mass variation, pH, zeta potential, droplet size, visual appearance, assay, and viscosity. No significant change was observed for mass variation, pH, zeta potential and droplet size over the three months for any of the different formulations stored at the different storage conditions. In addition, no significant change in colour was observed for the gel and emulgel formulations at pH 5 and 7.4 over the three months at all the storage conditions. However, it was observed that the formulations containing Pheroid™ showed a drastic change in colour at all the storage conditions. This might have been due to oxidation of certain components present in the Pheroid™ system. Consequently, further investigation is necessary to find the cause of the discolouration and a method to prevent it. The gel formulated at pH 5 depicted the formation of crystals. This might have been due to the fact that the solubility of ibuprofen was exceeded, leading to it precipitating from the formulation. A possible contributing factor to the varying assay values obtained during the study might have been due to non-homogenous sample withdrawal. On the other hand, no significant change was observed for the emulgel and Pheroid™ emulgel formulated at pH 5 and 7.4. The emulgel and Pheroid™ emulgel formulated at pH 5 depicted relative instability (according to the International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use, ICH) only at 40 °C/75% RH with a change in ibuprofen content of more than 5% (6.78 and 6.46%, respectively). The gel, emulgel and Pheroid™ emulgel at pH 7.4 exhibited the least variation in ibuprofen concentration at all of the storage conditions. This might indicate that the pH at which a semi-solid formulation is produced will have a direct influence on the stability of the product. No significant changes in viscosity (%RSD < 5) was observed for the gel and emulgel formulated at pH 7.4 and stored at 25 °C/60% RH. The remaining formulations at all of the specified storage conditions exhibited a significant change in viscosity (%RSD > 5) with a decrease in viscosity being more pronounced at the higher temperature and humidity storage conditions. A possible contributing factor to the change in viscosity over three months at the specified storage conditions might have been due to the use of Pluronic® F-127 (viscosity enhancer). This viscosity enhancer possesses a melting point of approximately 56 °C (BAST Corporation. s.a). The problem with this might have been the temperature (70 °C) at which the formulations were prepared. The higher preparation temperature might have caused the Pluronic® F-127 to degrade, thereby losing its ability to function appropriately. A balance must be maintained between optimum solubility and maximum stability (Pefile & Smith, 1997:148). Despite the lower skin permeation of the gel formulated at pH 7.4, this formulation performed the best, as it was considered stable (least variation during the 3 month stability test) and the obtained tape stripping results showed that this formulation depicted the highest ibuprofen concentrations in the stratum corneum and epidermis. Thus, topical as well as transdermal delivery were obtained. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Alkali compounds were added to a South African coal with a high swelling propensity and the behaviour of the blends were investigated. A vitrinite-rich bituminous coal from the Tshikondeni coal mine in the Limpopo province of South Africa was used. To reduce the influence of the minerals in the coal, the coal was partially demineralized by leaching with HCl and HF. The ash content of the coal sample was successfully reduced from 17.7% to 0.6%. KOH, KCl, K2CO3 and KCH3CO2 were then added to the demineralized coal in mass percentages of 1%, 4%, 5% and 10%. The free swelling indices (FSI) of the blends were determined and the samples were subjected to acquisition of TMA and TG-MS data. Addition of these potassium compounds to the demineralized coal reduced the swelling of the vitrinite-rich coal. From the free swelling indices of the various mixtures, it was concluded that the potassium compounds reduce the swelling of the coal in the following order of decreasing impact: KCH3CO2 > KOH > K2CO3 > KCl. From dilatometry experiments done on the blends with the 10% addition of potassium compounds, it was seen that with the addition of potassium compounds to the demineralized coal, a reduction in dilatation volume was obtained. The influence of the potassium compound in decreasing order: K2CO3> KOH> KCH3CO2> KCl. An increase in the softening temperature was observed for the demineralized coal-alkali blends. Thermogravimetric analyses were performed on the demineralized coal-potassium blended samples (<75 μm). These samples were pyrolyzed under a nitrogen atmosphere to a maximum temperature of 1200 °C using a heating rate of 10 °C/min. The relative reactivity for each of the blends with the different wt% addition was determined. From these results it was seen that KCH3CO2 increased the relative reactivity, whereas the KOH, KCl and K2CO3 showed an inhibiting influence. The attached mass spectrometer provided information on the low molecular mass gaseous products formed in the various temperature ranges as the thermal treatment proceeded. From the mass spectroscopy results, it was found that the potassium compounds decreased the temperature at which maximum evolution of H2 takes place. Thermomechanical analyses were performed on the 10 wt% addition of the potassium compounds to the demineralized coal. During TMA analyses, the sample was heated to 1000 °C using a heating rate of 10 °C/min. From the TMA result obtained it was clear that the addition of KCl did not have an influence on the swelling of the demineralized coal. All results are discussed. / MSc (Chemistry), North-West University, Potchefstroom Campus, 2014

A pharmaceutical dosage form is an entity that is administered to patients so that they receive an effective dose of an active pharmaceutical ingredient (API). The proper design and formulation of a transdermal dosage form require a thorough understanding of the physiological factors affecting percutaneous penetration and physicochemical characteristics of the API, as well as that of the pharmaceutical exipients that are used during formulation. The API and pharmaceutical excipients must be compatible with one another to produce a formulation that is stable, efficacious, attractive, easy to administer, and safe (Mahato, 2007:11). Amongst others, the physicochemical properties indicate the suitability of the type of dosage form, as well as any potential problems associated with instability, poor permeation and the target site to be reached (Wells & Aulton, 2002:337). Therefore, when developing new or improved dosage forms, it is of utmost importance to evaluate the factors influencing design and formulation to provide the best possible dosage form and formulation for the API in question. Delivery of an API through the skin has long been a promising concept due to its large surface area, ease of access, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the therapy. This is true whether a local or systemic pharmacological effect is desired (Aukunuru et al., 2007:856). However, most APIs are administered orally as this route is considered to be the simplest, most convenient and safest route of API administration. Since ibuprofen is highly metabolised in the liver and gastrointestinal tract, oral administration thereof results in decreased bioavailability. Furthermore, it also causes gastric mucosal damage, bleeding and ulceration. Another obstacle associated with oral API delivery is that some APIs require continuous delivery which is difficult to achieve (Bouwstra et al., 2003:3). Therefore, there is significant interest to develop topical dosage forms for ibuprofen to avoid side effects associated with oral delivery and to provide relatively consistent API levels at the application site for prolonged periods (Rhee et al., 2003:14). The aim of this study was to determine the influence of selected formulation factors on the transdermal delivery of ibuprofen. In order to achieve this aim, the physicochemical properties of ibuprofen had to be evaluated. The aqueous solubility, pH-solubility profile, octanol-water partition coefficient (log P-value) and octanol-buffer distribution coefficient (log D-values, pH 5 and 7.4) of ibuprofen were determined. According to Naik et al., (2000:319) the ideal aqueous solubility of APIs for transdermal delivery should be more than 1 mg.ml-1. However, results showed that ibuprofen depicted an aqueous solubility of 0.096 mg.ml-1 ± 25.483, which indicated poor water solubility and would therefore be rendered less favourable for transdermal delivery if only considering the aqueous solubility. The pH-solubility profile depicted that ibuprofen was less soluble at low pH-values and more soluble at higher pH-values. Previous research indicated that the ideal log Pvalues for transdermal API permeation of non steroid anti-inflammatory drugs (NSAIDs) are between 2 and 3 (Swart et al., 2005:72). Results obtained during this study indicated a log P-value of 4.238 for ibuprofen. This value was not included in the ideal range, which is an indication that the lipophilic/hydrophilic properties are not ideal, and this might therefore; contribute to poor ibuprofen penetration through the skin. Furthermore, the obtained log D-values at pH 5 and 7.4 were 3.105 and 0.386, respectively. Therefore, it would be expected that ibuprofen incorporated into a formulation prepared at a pH of 5 would more readily permeate the skin compared to ibuprofen incorporated into a formulation prepared at a pH of 7.4. A gel, an emulgel and a Pheroid™ emulgel were formulated at pH 5 and 7.4, in order to examine which dosage form formulated at which pH would deliver enhanced transdermal delivery. Obtained diffusion results of the different semi-solid formulations were furthermore compared to a South African marketed commercial product (Nurofen® gel) in order to establish if a comparable formulation could be obtained. An artificial membrane was used to conduct the membrane permeation studies over a period of 6 h, in order to determine whether ibuprofen was in fact released from the formulations through the membrane. Skin permeation studies were conducted using Franz diffusion cells over a period of 12 h where samples were withdrawn at specified time intervals. All the formulations exhibited an increase in the average cumulative amount of ibuprofen released from the formulations and that permeated the membrane when compared to Nurofen® gel. This increase was statistically significant (p<0.05) for the gel, emulgel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest cumulative amount of ibuprofen that permeated the membrane. Preparations formulated at a pH of 5, did not differ significantly from Nurofen® when the average cumulative amount of ibuprofen that permeated the membrane were compared. The following rank order for the average cumulative amount released from the formulations could be established: Gel (pH 7.4) >>>> Pheroid™ emulgel (pH 7.4) > Emulgel (pH 7.4) >>> Gel (pH 5)> Pheroid™ emulgel (pH 5) ≈ Emulgel (pH 5) > Nurofen® gel. On the other hand, all the formulations exhibited an increase in the average cumulative amount of ibuprofen that permeated the skin when compared to Nurofen® gel. This increase was statistically significant (p < 0.05) for the gel, emulgel and Pheroid™ emulgel at pH 5, as well as the emulgel and Pheroid™ emulgel at pH 7.4. The emulgel at pH 5 exhibited the highest cumulative amount of ibuprofen that permeated the skin. The following rank order for the average cumulative amount released from the formulations and that permeated the skin could be established: Emulgel (pH 5) >> Pheroid™ emulgel (pH 5) > Gel (pH 5) > Emulgel (pH 7.4)> Pheroid™ emulgel (pH 7.4) ≈ Emulgel (pH 7.4) >> Nurofen® gel > Gel (pH 7.4). From this rank order it was clear that a trend was followed where the pH of formulation also played a role in ibuprofen permeation. All the formulations exhibited a higher release rate and flux when compared to Nurofen® gel. This was statistically significant for the emulgel, gel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest release rate and flux. This was observed for the membrane and skin permeation studies. All the formulations (including Nurofen® gel) presented a correlation coefficient (r2) of 0.972 – 0.995 for membrane permeation studies, and 0.950 – 0.978 for skin permeation studies; indicating that the release of ibuprofen from each of the formulations could be described by the Higuchi model. Furthermore, all the formulations exhibited a prolonged lag time compared to Nurofen® gel which indicated that the ibuprofen was retained for a longer time by the base. This was statistically significant (p < 0.05) for the emulgel at pH 7.4, the gel and Pheroid™ emulgel at pH 5. The gel at pH 7.4 exhibited a lag time closest to that of Nurofen® gel and this difference could not be classified as statistically significant (p > 0.286). This was observed for the membrane and skin permeation studies. Nurofen® gel exhibited the highest ibuprofen concentration in the stratum corneum as well as in the epidermis followed by the gel at pH 7.4. However, results obtained for all the formulations indicated that topical as well as transdermal delivery of ibuprofen was achieved. The pH of a formulation plays an important role with respect to API permeation. Ibuprofen is reported to have a pKa value 4.4 (Dollery, 1999:I1); and by application of the Henderson-Hasselbach equation, at pH 5, 20.08% of ibuprofen will be present in its unionised form and at pH 7.4, 0.1% ibuprofen will exist in its unionised form. Since the unionised form of APIs is more lipid soluble than the ionised form, unionised forms of APIs permeate more readily across the lipid membranes (Surber & Smith, 2000:27). Therefore, it would be expected that ibuprofen formulated at pH 5 would be more permeable than formulations at pH 7.4. However, this did not correspond to the results (membrane studies) obtained in this study. It may be attributed to the solubility of ibuprofen in the different formulations. According to the pH-solubility profile of ibuprofen obtained in this study, it was more soluble at pH 7.4 than at pH 5. This was due to the fact that ibuprofen is a weak acidic compound, and for every 3 units away from the pKa-value, the solubility changes 10-fold (Mahato, 2007:14). However, with regard to the skin permeation studies, enhanced permeation was obtained with the formulations prepared at pH 5. This was in accordance with Corrigan et al., (2003:148) who stated that NSAIDs are less soluble and more permeable at low pH values, and more soluble and less permeable at high pH values. This was most probably due to the fact that unionised species, although possessing a lower aqueous solubility than the ionised species, resulted in enhanced skin permeation due to being more lipid-soluble. Finally, stability tests on the different semi-solid formulations for a period of three months at different temperature and humidity conditions were conducted to determine product stability. The formulations were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. Stability tests included: mass variation, pH, zeta potential, droplet size, visual appearance, assay, and viscosity. No significant change was observed for mass variation, pH, zeta potential and droplet size over the three months for any of the different formulations stored at the different storage conditions. In addition, no significant change in colour was observed for the gel and emulgel formulations at pH 5 and 7.4 over the three months at all the storage conditions. However, it was observed that the formulations containing Pheroid™ showed a drastic change in colour at all the storage conditions. This might have been due to oxidation of certain components present in the Pheroid™ system. Consequently, further investigation is necessary to find the cause of the discolouration and a method to prevent it. The gel formulated at pH 5 depicted the formation of crystals. This might have been due to the fact that the solubility of ibuprofen was exceeded, leading to it precipitating from the formulation. A possible contributing factor to the varying assay values obtained during the study might have been due to non-homogenous sample withdrawal. On the other hand, no significant change was observed for the emulgel and Pheroid™ emulgel formulated at pH 5 and 7.4. The emulgel and Pheroid™ emulgel formulated at pH 5 depicted relative instability (according to the International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use, ICH) only at 40 °C/75% RH with a change in ibuprofen content of more than 5% (6.78 and 6.46%, respectively). The gel, emulgel and Pheroid™ emulgel at pH 7.4 exhibited the least variation in ibuprofen concentration at all of the storage conditions. This might indicate that the pH at which a semi-solid formulation is produced will have a direct influence on the stability of the product. No significant changes in viscosity (%RSD < 5) was observed for the gel and emulgel formulated at pH 7.4 and stored at 25 °C/60% RH. The remaining formulations at all of the specified storage conditions exhibited a significant change in viscosity (%RSD > 5) with a decrease in viscosity being more pronounced at the higher temperature and humidity storage conditions. A possible contributing factor to the change in viscosity over three months at the specified storage conditions might have been due to the use of Pluronic® F-127 (viscosity enhancer). This viscosity enhancer possesses a melting point of approximately 56 °C (BAST Corporation. s.a). The problem with this might have been the temperature (70 °C) at which the formulations were prepared. The higher preparation temperature might have caused the Pluronic® F-127 to degrade, thereby losing its ability to function appropriately. A balance must be maintained between optimum solubility and maximum stability (Pefile & Smith, 1997:148). Despite the lower skin permeation of the gel formulated at pH 7.4, this formulation performed the best, as it was considered stable (least variation during the 3 month stability test) and the obtained tape stripping results showed that this formulation depicted the highest ibuprofen concentrations in the stratum corneum and epidermis. Thus, topical as well as transdermal delivery were obtained. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

The De Witte (2000) Job Insecurity Scale (JIS) claims to measure the cognitive and affective dimensionalities of job insecurity. However, there is a concern as to whether this is in fact a true reflection of the individual, owing to the possibility that the JIS may rather measure the negative and positive dimensionalities of job insecurity instead. This research article aims to investigate whether a revised version of the JIS measures the cognitive and affective dimensionalities of job insecurity, or alternatively, other dimensionalities of the revised JIS after additional items have been added to the scale. Furthermore, it is aimed at determining whether the constructs of the revised JIS prove to be invariant across gender, age and educational level, and to determine whether the psychometric properties of a revised version of the JIS is a valid and reliable instrument. Furthermore, this research article aims at determining if the revised version of the JIS is a more accurate indicator of job insecurity and its relation with organisational outcomes (job satisfaction and organisational commitment), as well as its equivalence across various demographic variables (i.e. gender, age and educational level). A quantitative research approach was used. This approach was utilised to statistically reflect the psychometric properties of the revised version of the JIS, using large amounts of data relating to job insecurity. A cross-sectional design was used for the purpose of this study. The sample consisted of employees working in the mining sector (n = 262) and manufacturing industries (n = 208), constituting a total sample of 470 (n = 470). Non-probability quota sampling was used to adequately divide the population according to its sector in the economy, and further according to the industry. The results showed that the revised JIS consists of a two-factor model, namely job security and job insecurity. Furthermore, it was found that the revised JIS is valid in providing relationships with organisational outcomes (job satisfaction and organisational commitment). The study indicated that job insecurity has a negative relationship with job satisfaction, as well as a predictive positive relationship with organisational commitment. The revised JIS proved to have discriminant validity in that it does not relate to an unrelated construct (physical tiredness during work). Lastly, the revised JIS can be deemed valid across different demographic groups (gender, age and educational level). Recommendations are made to be applied in practice, as well as for future research. / MA (Industrial Psychology), North-West University, Potchefstroom Campus, 2015

The De Witte (2000) Job Insecurity Scale (JIS) claims to measure the cognitive and affective dimensionalities of job insecurity. However, there is a concern as to whether this is in fact a true reflection of the individual, owing to the possibility that the JIS may rather measure the negative and positive dimensionalities of job insecurity instead. This research article aims to investigate whether a revised version of the JIS measures the cognitive and affective dimensionalities of job insecurity, or alternatively, other dimensionalities of the revised JIS after additional items have been added to the scale. Furthermore, it is aimed at determining whether the constructs of the revised JIS prove to be invariant across gender, age and educational level, and to determine whether the psychometric properties of a revised version of the JIS is a valid and reliable instrument. Furthermore, this research article aims at determining if the revised version of the JIS is a more accurate indicator of job insecurity and its relation with organisational outcomes (job satisfaction and organisational commitment), as well as its equivalence across various demographic variables (i.e. gender, age and educational level). A quantitative research approach was used. This approach was utilised to statistically reflect the psychometric properties of the revised version of the JIS, using large amounts of data relating to job insecurity. A cross-sectional design was used for the purpose of this study. The sample consisted of employees working in the mining sector (n = 262) and manufacturing industries (n = 208), constituting a total sample of 470 (n = 470). Non-probability quota sampling was used to adequately divide the population according to its sector in the economy, and further according to the industry. The results showed that the revised JIS consists of a two-factor model, namely job security and job insecurity. Furthermore, it was found that the revised JIS is valid in providing relationships with organisational outcomes (job satisfaction and organisational commitment). The study indicated that job insecurity has a negative relationship with job satisfaction, as well as a predictive positive relationship with organisational commitment. The revised JIS proved to have discriminant validity in that it does not relate to an unrelated construct (physical tiredness during work). Lastly, the revised JIS can be deemed valid across different demographic groups (gender, age and educational level). Recommendations are made to be applied in practice, as well as for future research. / MA (Industrial Psychology), North-West University, Potchefstroom Campus, 2015

The changing work environment has caused individuals to revise and change their career decisions. This creates career uncertainty, which has become a widespread problem, particularly for students. When this problem is not addressed, it leads to career indecision, or less optimal choices which could influence career opportunities and quality of life. Career indecision could impact on organisations, resulting in problems such as person–job adjustment, lack of engagement and burnout. Although research on career uncertainty is available internationally, there is limited research on career uncertainty and its antecedents in the South African context. Career uncertainty can have short– and long–term effects on the individual. This study therefore contributes toward the gap in research on the antecedents of career uncertainty. Given that career uncertainty is a problem that individuals are constantly confronted with, it is important that the antecedents of this be investigated. The objectives of this study were to 1) conceptualise the antecedents of career uncertainty according to the literature; 2) determine if socio–demographic characteristics (gender, career guidance, help from parents, help from other individuals and work experience) are significant predictors of career uncertainty; 3) determine if personality characteristics (self–esteem, self–efficacy and neuroticism) are significant predictors of career uncertainty; 4) determine if career decision–making difficulties are significant predictors of career uncertainty; 5) determine if student burnout and student engagement are significant predictors of career uncertainty; and 6) determine if academic performance is a significant predictor of career uncertainty. A non–probability quota sample (N = 782) was used to investigate antecedents of career uncertainty in a sample of university students. Career uncertainty was measured by one item The changing work environment has caused individuals to revise and change their career decisions. This creates career uncertainty, which has become a widespread problem, particularly for students. When this problem is not addressed, it leads to career indecision, or less optimal choices which could influence career opportunities and quality of life. Career indecision could impact on organisations, resulting in problems such as person–job adjustment, lack of engagement and burnout. Although research on career uncertainty is available internationally, there is limited research on career uncertainty and its antecedents in the South African context. Career uncertainty can have short– and long–term effects on the individual. This study therefore contributes toward the gap in research on the antecedents of career uncertainty. Given that career uncertainty is a problem that individuals are constantly confronted with, it is important that the antecedents of this be investigated. The objectives of this study were to 1) conceptualise the antecedents of career uncertainty according to the literature; 2) determine if socio–demographic characteristics (gender, career guidance, help from parents, help from other individuals and work experience) are significant predictors of career uncertainty; 3) determine if personality characteristics (self–esteem, self–efficacy and neuroticism) are significant predictors of career uncertainty; 4) determine if career decision–making difficulties are significant predictors of career uncertainty; 5) determine if student burnout and student engagement are significant predictors of career uncertainty; and 6) determine if academic performance is a significant predictor of career uncertainty. A non–probability quota sample (N = 782) was used to investigate antecedents of career uncertainty in a sample of university students. Career uncertainty was measured by one item consisting of four categories: I am very sure; I know exactly what career I will pursue (n = 228), I am fairly sure what career I will pursue (n = 416), I am not sure at all which career I will pursue (n = 135) and I do not plan to follow a career (n = 3). For the objective of the study, categories one and two were grouped together with participants who were fairly certain which career they would follow, while participants in category three represented participants who were uncertain. Category four was not included as only three participants within that category answered. In total, 644 students were (fairly) certain, while 135 were uncertain. These two groups were enclosed as a dependent variable in the logistic regression. The results of this study showed that work experience influences career uncertainty to some extent. This is supported by previous research. Furthermore, it was found that self–esteem also influences career uncertainty to some degree. However, these two variables were only significant in the first steps of the logistic regression. Furthermore, the results showed that career decision–making difficulties share a significant relationship with career uncertainty. The study also found that significant antecedents of career uncertainty include: a lack of information about the decision–making process; a lack of information about occupations; inconsistent information due to internal conflict; a lack of information about ways of obtaining information; and inconsistent information due to external conflict. In conclusion, exhaustion, cynicism and dedication were also found to be significant antecedents of career uncertainty. Based on these results, this study suggests that student burnout and student engagement influence an individual’s level of career uncertainty. Recommendations were made for practice as well as for future research. / Thesis (M.A. (Industrial Psychology))--North-West University, Potchefstroom Campus, 2012.

The changing work environment has caused individuals to revise and change their career decisions. This creates career uncertainty, which has become a widespread problem, particularly for students. When this problem is not addressed, it leads to career indecision, or less optimal choices which could influence career opportunities and quality of life. Career indecision could impact on organisations, resulting in problems such as person–job adjustment, lack of engagement and burnout. Although research on career uncertainty is available internationally, there is limited research on career uncertainty and its antecedents in the South African context. Career uncertainty can have short– and long–term effects on the individual. This study therefore contributes toward the gap in research on the antecedents of career uncertainty. Given that career uncertainty is a problem that individuals are constantly confronted with, it is important that the antecedents of this be investigated. The objectives of this study were to 1) conceptualise the antecedents of career uncertainty according to the literature; 2) determine if socio–demographic characteristics (gender, career guidance, help from parents, help from other individuals and work experience) are significant predictors of career uncertainty; 3) determine if personality characteristics (self–esteem, self–efficacy and neuroticism) are significant predictors of career uncertainty; 4) determine if career decision–making difficulties are significant predictors of career uncertainty; 5) determine if student burnout and student engagement are significant predictors of career uncertainty; and 6) determine if academic performance is a significant predictor of career uncertainty. A non–probability quota sample (N = 782) was used to investigate antecedents of career uncertainty in a sample of university students. Career uncertainty was measured by one item The changing work environment has caused individuals to revise and change their career decisions. This creates career uncertainty, which has become a widespread problem, particularly for students. When this problem is not addressed, it leads to career indecision, or less optimal choices which could influence career opportunities and quality of life. Career indecision could impact on organisations, resulting in problems such as person–job adjustment, lack of engagement and burnout. Although research on career uncertainty is available internationally, there is limited research on career uncertainty and its antecedents in the South African context. Career uncertainty can have short– and long–term effects on the individual. This study therefore contributes toward the gap in research on the antecedents of career uncertainty. Given that career uncertainty is a problem that individuals are constantly confronted with, it is important that the antecedents of this be investigated. The objectives of this study were to 1) conceptualise the antecedents of career uncertainty according to the literature; 2) determine if socio–demographic characteristics (gender, career guidance, help from parents, help from other individuals and work experience) are significant predictors of career uncertainty; 3) determine if personality characteristics (self–esteem, self–efficacy and neuroticism) are significant predictors of career uncertainty; 4) determine if career decision–making difficulties are significant predictors of career uncertainty; 5) determine if student burnout and student engagement are significant predictors of career uncertainty; and 6) determine if academic performance is a significant predictor of career uncertainty. A non–probability quota sample (N = 782) was used to investigate antecedents of career uncertainty in a sample of university students. Career uncertainty was measured by one item consisting of four categories: I am very sure; I know exactly what career I will pursue (n = 228), I am fairly sure what career I will pursue (n = 416), I am not sure at all which career I will pursue (n = 135) and I do not plan to follow a career (n = 3). For the objective of the study, categories one and two were grouped together with participants who were fairly certain which career they would follow, while participants in category three represented participants who were uncertain. Category four was not included as only three participants within that category answered. In total, 644 students were (fairly) certain, while 135 were uncertain. These two groups were enclosed as a dependent variable in the logistic regression. The results of this study showed that work experience influences career uncertainty to some extent. This is supported by previous research. Furthermore, it was found that self–esteem also influences career uncertainty to some degree. However, these two variables were only significant in the first steps of the logistic regression. Furthermore, the results showed that career decision–making difficulties share a significant relationship with career uncertainty. The study also found that significant antecedents of career uncertainty include: a lack of information about the decision–making process; a lack of information about occupations; inconsistent information due to internal conflict; a lack of information about ways of obtaining information; and inconsistent information due to external conflict. In conclusion, exhaustion, cynicism and dedication were also found to be significant antecedents of career uncertainty. Based on these results, this study suggests that student burnout and student engagement influence an individual’s level of career uncertainty. Recommendations were made for practice as well as for future research. / Thesis (M.A. (Industrial Psychology))--North-West University, Potchefstroom Campus, 2012.

Over the past few decades it has become evident that the work/family interface is a much broader concept that does not only stress the negative side of the relationship, but also include a positive side. This refers to the process by which participation in one role (e.g. work role) is made better or easier by virtue of participation in the other role (e.g. family role). South Africa is a multicultural society, which consists of four groups (i.e. Black, White, Coloured and Indian), speaking eleven official languages. All of these groups are faced with unique and different circumstances. Apart from cultural, ethnic and linguistic differences, other divergent elements may exist (i.e. values and norms). Therefore South African employees may experience the positive side of the work/family interface differently from employees within other countries. To add to the problem, it is not clear how South African employees‟ experiences of enrichment between work and family domains compare to the experiences of employees in other countries. Furthermore, to date no measuring instrument to assess the enrichment between work and family domains in both directions (work-to-family and family-to-work) exists, that is unique to the South African context. This could pose potential problems for organisations and for future studies on the positive side of work/family in South Africa. The objectives of this research were 1) to determine how the positive side of the work/family interface, particularly work-family enrichment, is conceptualised according to the literature; 2) to develop a new work-family enrichment instrument that is suitable for the South African context and that addresses conceptual and measurement issues relating to previous positive measurements of the work/family interface; 3) to investigate the psychometric properties of the newly developed work-family enrichment instrument; and 4) to assess antecedents and outcomes of work-family enrichment among employees within the South African context. The study consisted of four phases. During the first phase, following an extensive review of literature covering the positive side of the work/family interface, a theoretical framework was proposed for the study. Thereafter, a new instrument that measures work-family enrichment was developed based on the proposed theoretical framework. The instrument was tested via Rasch modelling with a pre-limenary study (N = 527), in order to overcome some of the measurement limitations from the previous positive work-family instruments. This test was followed by investigating the psychometric properties (i.e. construct validity, discriminant validity, convergent validity and external validity; N = 627) of the newly developed MACE Work-Family Enrichment Instrument. During the final phase, antecedents, work-family enrichment and outcomes were assessed in the South African context. In both phases 3 and 4, the following instruments (accompanied by the new instrument) were utilised, namely the Work Resources Scale, Home Resources Scale, Utrecht Work Engagement Scale, Family Engagement Scale, Job Satisfaction Scale, Career Satisfaction Scale, Life Satisfaction Scale, Family Satisfaction Scale and the Work-family Enrichment Scale. During the first phase, the literature revealed that the positive side of the work-family interface is presented by various concepts (i.e. work-family enhancement, work-family facilitation, work-family positive spillover and work-family enrichment). The review also revealed that, to date, the work-family enrichment concept has been the only concept in literature on the positive work/family interface that is grounded in a properly developed conceptualised theoretical model. The fundamental thinking behind the work-family enrichment model is that work and family each provides individuals with resources (i.e. skills and perspectives, psychological and physical, social-capital, flexibility, material) in the one domain, that may help the individual improve the quality of his/her performance in the other domain. These resources thus enable improved performance in the other role either directly (i.e. instrumental path) or indirectly (i.e. affective path). During the second phase a new work-family enrichment instrument was developed, namely the MACE Work-Family Enrichment Instrument. This instrument was based on the proposed work-family enrichment theoretical model for both directions (i.e. work-to-family and family-to-work). Initially 133 items were developed that the researcher obtained from the existing literature, and 161 items were self-developed. During the evaluation study, various problematic items were eliminated by using the Rasch measurement model. The third phase included the validation study in which the psychometric properties of the new MACE instrument was investigated. The results provided evidence for construct validity, discriminant validity and convergent validity, and showed significant relations with external variables. Adequate internal consistency was also found for the proposed scales. The final number of items retained after this phase in the development and pilot study of the MACE Work-Family Enrichment Instrument were 34. During the final phase, various relationships were pointed out between antecedents (i.e. various work resources and home resources), work-family enrichment dimensions, as well as dimensions and outcomes of this type of enrichment. These included work-engagement dimensions, family engagement dimensions, as well as satisfaction-dimensions for work, career, life and the family environment. The results of these relationships were found to be in accordance with other literature on the positive side of the work/family interface. The present study provided evidence for the psychometric properties of the new MACE instrument, which researchers and managers can use to investigate the specific enrichment between work and family domains of employees in a South African context. The results give researchers and managers insight into the specific antecedents (e.g. work resources) and outcomes (e.g. job satisfaction) that play a role in work-family enrichment. This insight can be used as basis on which interventions can be developed to deal with these issues currently. Recommendations were also made for future research. / PhD (Industrial Psychology), North-West University, Potchefstroom Campus, 2014