Dosage forms have been developed over the years for various applications. The dosage form consists of the active drug in combination with pharmaceutical excipients. The pharmaceutical excipients solubilise, suspend, thicken, dilute, emulsify, stabilise, preserve, colour and flavour medicinal agents into efficacious and appealing dosage forms. The dosage form under investigation in this study is of the oral type. The Pheroid® is a unique drug delivery system which consists of an oil-in-water emulsion system. Emulsion based drug systems provide a suitable medium for the delivery of both hydrophobic and hydrophilic drugs which can be incorporated into its oil or water phase for delivery to the site of action. These advantages make them more efficient as dosage form. Emulgels are either emulsion of oil-in-water or water-in-oil type, which is gelled by mixing with gelling agents. Incorporation of emulsion into gel increases its stability and makes it a dual control release system. The presence of the gel phase makes it a non-greasy formulation which favours good patient compliance. A strategy followed to improve the stability of the emulgel system is the packaging of the formula into single dose sachets to protect the product against physical and chemical breakdown during patient usage. All factors such as selection of gelling agent, preservatives and formulation methods influencing the stability and efficacy of Pheroid® emulgel are discussed. In this study, three different emulsifiers were added to the formula and the analysis of visual appearance, pH measurements, rheological studies, light microscopy and confocol laser scanning microscopy (CLSM) will provide an insight to the potential usage of emulgel as drug delivery system. A range of para-hydroxybenzoate esters was tested in the Pheroid® emulgel and the most suitable candidate chosen for further accelerated stability testing. It was thus possible to prepare a single dose emulgel with Carbopol® 934P (0.2% w/v) as an emulsifier, with Nipastat® (0.175% w/v) and PG (10% v/v) as preservatives into a stable dosage form suitable for further product development. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Previous studies have shown that the formulation of an active pharmaceutical ingredient (API) entrapped in the Pheroid® (Pheroid for simplification) delivery system enhances absorption of the API, suppresses its metabolism, and may contribute to an increase in the quantity of the API present at the site of action. Higher drug levels at the active site should particularly increase the effectiveness of a drug with a narrow therapeutic index and reduce the incidence of the resistance that may otherwise arise if the sub-therapeutic levels of the API are in contact with the site of interest. Two approaches were followed in this study. First, the radioactive tracer molecule 99mTechnetium methylene diphosphonate (99mTc MDP) was used. Intravenously injected 99mTc MDP is an extremely effective bone-seeking radiopharmaceutical used in the diagnosis of bone disorders such as bone metastases in patients. However, if entrapped inside a Pheroid vesicle, it will locate to that site, usually an organ, where the Pheroid vesicles may tend to accumulate. Experiments conducted with 99mTc MDP alone or with Pheroid will therefore establish how efficiently Pheroid vesicles localize and will also indicate the preferred site of localization inside a body. The process would involve the oral administration of 99mTc MDP either alone or with Pheroid, involving an animal model. It would also involve tracking localization to particular organs, blood or other sites. The second approach requires the use of chloroquine (CQ) labeled with carbon-14 (14C-CQ,) to compare absorption of the drug both with and without the Pheroid system. The intention was to compare oral absorption and bio-distribution of 14C-CQ administered either alone or entrapped in the Pheroid system. It was also possible to establish whether the Pheroid affects the biological half-lives of the CQ and residence times of CQ in the different organs of the body. Absorption of free 99mTc MDP (orally adminsistered) through the intestinal tract is negligible but it was anticipated that increased absorption will be observed when 99mTc MDP was entrapped in the Pheroid system. In the 99mTc MDP study, different routes of administration of 99mTc MDP, as well as 99mTc MDP entrapped and not entrapped in the Pheroid system, were investigated. The Sprague Dawley rat was used as animal model. Rats were divided into three groups of four rats each for the first part of the study. In the first group, only 99mTc MDP was injected intravenously in order to establish natural distribution of the 99mTc MDP. For the second group, 99mTc MDP was administered orally in order to establish whether there was any absorption through the intestinal tract. In the third group, the 99mTc MDP was entrapped in Pheroid vesicles and this formulation was administered orally in order to establish whether the Pheroid system enhanced oral absorption. The animals were sacrificed four hours after administration and organs were harvested and were counted for radioactivity to determine the percentage of injected/administrated dose in each organ. After oral administration, the Pheroid system was found to have facilitated absorption of 99mTc MDP through the intestinal tract into the blood. 99mTc MDP concentrations in the femur, although lower, were still comparable with that observed after intravenous administration of 99mTc MDP in the absence of Pheroid. Thus, overall, excellent absorption of the Pheroid entrapped 99mTc MDP through the intestinal tract was seen in contrast to little or zero absorption of the compound in the reference formulations. The half-life of the radio-labelled compound in the blood was prolonged after oral administration owing to the Pheroid. To investigate the bio-distribution of radioactive chloroquine (14C-CQ) Sprague Dawley rats were divided into two groups of four rats each. In the first group, 14C-CQ in deionised (DI) water was administered orally, and in the second group 14C-CQ entrapped in Pheroid vesicles was administered, also orally. The animals were sacrificed one, two and four hours after administration and subjected to comprehensive macroscopic inspection. All the organs were harvested and radioactivity was determined with liquid scintillation after applicable sample preparation. The Pheroid system produced much higher organ and blood concentrations of 14C-CQ and enhanced residence times within the organs and blood in comparison with that of 14C-CQ administered alone. Commercial applications of these results are possible, as a number of radiopharmaceutical products can presently be administered only intravenously. The added potential of these new Pheroid formulations could be of significance in the treatment of malaria, as chloroquine is inexpensive and widely available. Another point of interest is that the use of these formulations may enable micromolar drug concentrations to be achieved using drug dosage regimes that usually produce only nanomolar levels. However, safety aspects would have to be carefully monitored. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

Dosage forms have been developed over the years for various applications. The dosage form consists of the active drug in combination with pharmaceutical excipients. The pharmaceutical excipients solubilise, suspend, thicken, dilute, emulsify, stabilise, preserve, colour and flavour medicinal agents into efficacious and appealing dosage forms. The dosage form under investigation in this study is of the oral type. The Pheroid® is a unique drug delivery system which consists of an oil-in-water emulsion system. Emulsion based drug systems provide a suitable medium for the delivery of both hydrophobic and hydrophilic drugs which can be incorporated into its oil or water phase for delivery to the site of action. These advantages make them more efficient as dosage form. Emulgels are either emulsion of oil-in-water or water-in-oil type, which is gelled by mixing with gelling agents. Incorporation of emulsion into gel increases its stability and makes it a dual control release system. The presence of the gel phase makes it a non-greasy formulation which favours good patient compliance. A strategy followed to improve the stability of the emulgel system is the packaging of the formula into single dose sachets to protect the product against physical and chemical breakdown during patient usage. All factors such as selection of gelling agent, preservatives and formulation methods influencing the stability and efficacy of Pheroid® emulgel are discussed. In this study, three different emulsifiers were added to the formula and the analysis of visual appearance, pH measurements, rheological studies, light microscopy and confocol laser scanning microscopy (CLSM) will provide an insight to the potential usage of emulgel as drug delivery system. A range of para-hydroxybenzoate esters was tested in the Pheroid® emulgel and the most suitable candidate chosen for further accelerated stability testing. It was thus possible to prepare a single dose emulgel with Carbopol® 934P (0.2% w/v) as an emulsifier, with Nipastat® (0.175% w/v) and PG (10% v/v) as preservatives into a stable dosage form suitable for further product development. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Previous studies have shown that the formulation of an active pharmaceutical ingredient (API) entrapped in the Pheroid® (Pheroid for simplification) delivery system enhances absorption of the API, suppresses its metabolism, and may contribute to an increase in the quantity of the API present at the site of action. Higher drug levels at the active site should particularly increase the effectiveness of a drug with a narrow therapeutic index and reduce the incidence of the resistance that may otherwise arise if the sub-therapeutic levels of the API are in contact with the site of interest. Two approaches were followed in this study. First, the radioactive tracer molecule 99mTechnetium methylene diphosphonate (99mTc MDP) was used. Intravenously injected 99mTc MDP is an extremely effective bone-seeking radiopharmaceutical used in the diagnosis of bone disorders such as bone metastases in patients. However, if entrapped inside a Pheroid vesicle, it will locate to that site, usually an organ, where the Pheroid vesicles may tend to accumulate. Experiments conducted with 99mTc MDP alone or with Pheroid will therefore establish how efficiently Pheroid vesicles localize and will also indicate the preferred site of localization inside a body. The process would involve the oral administration of 99mTc MDP either alone or with Pheroid, involving an animal model. It would also involve tracking localization to particular organs, blood or other sites. The second approach requires the use of chloroquine (CQ) labeled with carbon-14 (14C-CQ,) to compare absorption of the drug both with and without the Pheroid system. The intention was to compare oral absorption and bio-distribution of 14C-CQ administered either alone or entrapped in the Pheroid system. It was also possible to establish whether the Pheroid affects the biological half-lives of the CQ and residence times of CQ in the different organs of the body. Absorption of free 99mTc MDP (orally adminsistered) through the intestinal tract is negligible but it was anticipated that increased absorption will be observed when 99mTc MDP was entrapped in the Pheroid system. In the 99mTc MDP study, different routes of administration of 99mTc MDP, as well as 99mTc MDP entrapped and not entrapped in the Pheroid system, were investigated. The Sprague Dawley rat was used as animal model. Rats were divided into three groups of four rats each for the first part of the study. In the first group, only 99mTc MDP was injected intravenously in order to establish natural distribution of the 99mTc MDP. For the second group, 99mTc MDP was administered orally in order to establish whether there was any absorption through the intestinal tract. In the third group, the 99mTc MDP was entrapped in Pheroid vesicles and this formulation was administered orally in order to establish whether the Pheroid system enhanced oral absorption. The animals were sacrificed four hours after administration and organs were harvested and were counted for radioactivity to determine the percentage of injected/administrated dose in each organ. After oral administration, the Pheroid system was found to have facilitated absorption of 99mTc MDP through the intestinal tract into the blood. 99mTc MDP concentrations in the femur, although lower, were still comparable with that observed after intravenous administration of 99mTc MDP in the absence of Pheroid. Thus, overall, excellent absorption of the Pheroid entrapped 99mTc MDP through the intestinal tract was seen in contrast to little or zero absorption of the compound in the reference formulations. The half-life of the radio-labelled compound in the blood was prolonged after oral administration owing to the Pheroid. To investigate the bio-distribution of radioactive chloroquine (14C-CQ) Sprague Dawley rats were divided into two groups of four rats each. In the first group, 14C-CQ in deionised (DI) water was administered orally, and in the second group 14C-CQ entrapped in Pheroid vesicles was administered, also orally. The animals were sacrificed one, two and four hours after administration and subjected to comprehensive macroscopic inspection. All the organs were harvested and radioactivity was determined with liquid scintillation after applicable sample preparation. The Pheroid system produced much higher organ and blood concentrations of 14C-CQ and enhanced residence times within the organs and blood in comparison with that of 14C-CQ administered alone. Commercial applications of these results are possible, as a number of radiopharmaceutical products can presently be administered only intravenously. The added potential of these new Pheroid formulations could be of significance in the treatment of malaria, as chloroquine is inexpensive and widely available. Another point of interest is that the use of these formulations may enable micromolar drug concentrations to be achieved using drug dosage regimes that usually produce only nanomolar levels. However, safety aspects would have to be carefully monitored. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

HIV/AIDS is the most threatening and challenging infectious diseases of our time, with the highest increase of newly infected cases reported. This infectious disease was discovered in the early eighties under homosexual men and was later to be discovered in heterosexuals. HIV is a systemic immunosuppressive disorder which causes a depletion of CD4+ T cells and develops into the acquired immunodeficiency syndrome - AIDS. Africa is the continent most affected by HIV/AIDS with the southern parts of Africa having the highest prevalence rates compared to the rest of Africa. Statistics indicate that AIDS is responsible for 3% of deaths in children worldwide - one in seven people dying of an HIV-related illness is a child under the age of 15 years. It was stated by the WHO that countries should develop improved antiretrovirals regimes for the prevention of mother-to-child transmission. Difficulties in administering antiretrovirals (ARVs) to patients (especially children) are the strict dosage regimes and the severe adverse reactions. These factors complicate patient adherence. The list of problems in treating patients is endless and includes the distribution, stability as well as the low efficacy of these drugs. Most of the above mentioned problems and obstacles related to ARVs and ARV treatment could be minimized or eliminated by the use of a stable and effective drug delivery system. Enhancing ARV treatment may be accomplished by the use of the Pheroid™ drug delivery system. Pheroids™ consists mainly of fatty acids and sterile nitrous oxide gassed water. Pharmacological active substances are entrapped into submicron and micron sized structures called Pheroids™. Research showed promising results and advantages in delivering drugs through oral and transdermal routes using Pheroid™ technology. The focus of this study was to test the possible enhancement of the efficacy of antiretrovirals using Pheroid™ technology. The assays used to study this possible enhancement were a modified neutral red and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. These assays confirmed and illustrated the toxic and protective properties of the tested ARVs (stavudine, lamivudine and nevirapine). An MT-2 cell line was used and infected with an HIV-1 strain, SW7-TCL. Applying Pheroid™ technology in these assays resulted in massive cell death, due to increased ARV toxic levels within the cells. Viability tests proved that Pheroids™ had no effect on the viability of cells at the concentration typically used. This confirmed the enhancing properties of Pheroids™ in the delivery of drugs into the cells. The MTT assay was further adapted from a seven day incubation period to a three day incubation period. By using a low concentration series and a three day incubation period the loss of cells through toxicity was partially overcome. One of the problems that arose form this study was the non-reproducibility of the results. Absorbance levels fluctuated at specific concentrations of the same ARV, which cause difficulties in comparing results. This result was repeatedly confirmed in this syncytium forming infection model. In conclusion, Pheroid™ technology enhanced the delivery of ARVs into the cells although it resulted in cell death. Both the neutral red and MTT assays were found to be inaccurate but further development, research and assay optimization could result in improved in vitro studies. The article format was used for this thesis, as described in the general academic rules in section A.13.7.3 of the North West University. Chapter 1 deals with HIV/AIDS related problems, statistics and treatment obstacles. Chapter 2 is a summary of the cell viability assays used in this study. Pheroid™ technology and its application to ARV treatment are dealt with in chapter 3. The proposed article for submission in the journal Cell Death and Differentiation has been included in chapter 4. Some of the results from the study are reported in the article and annexures, whilst other results are shown and discussed in Chapter 5. Chapter 6 gives a conclusion and final summary of this study. All other experimental methods and results are enclosed in the annexures, as is the "Guide for authors" for the article. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

The aim of this study was to investigate the effect of different penetration enhancers containing essential fatty acids (EFAs) on the transdermal delivery of flurbiprofen. Flurbiprofen was used as a marker / model compound. Fatty acids were chosen as penetration enhancers for their ability to reversibly increase skin permeability through entering the lipid bilayers and disrupting their ordered domains. Fatty acids are natural, non-toxic compounds (Karande & Mitragotri, 2009:2364). Evening primrose oil, vitamin F and Pheroid™ technology all contain fatty acids and were compared using a cream based-formulation. This selection was to ascertain whether EFAs exclusively, or EFAs in a delivery system, would have a significant increase in the transdermal delivery of a compound. For an active pharmaceutical ingredient (API) to be effectively delivered transdermally, it has to be soluble in lipophilic, as well as hydrophilic mediums (Naik et al., 2000:319; Swart et al., 2005:72). This is due to the intricate structure of the skin, where the stratum corneum (outermost layer) is the primary barrier, which regulates skin transport (Barry, 2001:102; Moser et al., 2001:103; Venus et al., 2010:469). Flurbiprofen is highly lipophilic (log P = 4.24) with poor aqueous solubility. It has a molecular weight lower than 500 g/mol indicating that skin permeation may be possible, though the high log P indicates that some difficulty is to be expected (Dollery, 1999:F126; Hadgraft, 2004:292; Swart et al., 2005:72; Karande & Mitragotri, 2009:2363; Drugbank, 2012). In vitro transdermal diffusion studies (utilising vertical Franz diffusion cells) were conducted, using donated abdominal skin from Caucasian females. The studies were conducted over 12 h with extractions of the receptor phase every 2 h to ensure sink conditions. Prior to skin diffusion studies, membrane release studies were performed to determine whether the API was released from the formulation. Membrane release studies were conducted over 6 h and extractions done hourly. Tape stripping experiments were performed on the skin circles after 12 h diffusion studies to determine the concentration flurbiprofen present in the stratum corneum and dermisepidermis. The flurbiprofen concentrations present in the samples were determined using high performance chromatography and a validated method. Membrane release results indicated the following rank order for flurbiprofen from the different formulations: vitamin F > control > evening primrose oil (EPO) >> Pheroid™. The control formulation contained only flurbiprofen and no penetration enhancers. Skin diffusion results on the other hand, indicated that flurbiprofen was present in the stratum corneum and the dermisepidermis. The concentration flurbiprofen present in the receptor phase of the Franz cells (representing human blood) followed the subsequent rank order: EPO > control > vitamin F >> Pheroid™. All the formulations stipulated a lag time shorter than that of the control formulation (1.74 h), with the EPO formulation depicting the shortest (1.36 h). The control formulation presented the highest flux (8.41 μg/cm2.h), with the EPO formulation following the closest (8.12 μg/cm2.h). It could thus be concluded that fatty acids exclusively, rather than in a delivery system, had a significant increase in the transdermal delivery of flurbiprofen. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Local anaesthetics are used regularly in the medical world for a variety of different procedures. Topical anaesthetics are used largely in minor skin breaking procedures, laceration repair and minor surgical procedures such as laryngoscopy, oesophagoscopy or urethroscopy (Franchi et al., 2008:186e1). The topical means of application of a local anaesthetic is non-invasive and painless that results in a good patient acceptability profile (Little et al., 2008:102). An existing commercial topical anaesthetic product contains a eutectic mixture of the amide-type local anaesthetics lidocaine hydrochloride (HCl) and prilocaine hydrochloride (HCl). This commercial product takes up to an hour to produce an anaesthetic effect. This is considered as a disadvantage in the use of topical anaesthetics, an hour waiting time is not always ideal in certain medical circumstances (Wahlgren & Quiding, 2000:584). This study compared the lag times, transdermal and topical delivery of lidocaine HCl and prilocaine HCl from four different semi-solid formulations with the inclusion of a current commercial product. One of the formulated semi-solid formulations included Pheroid™ technology, a novel skin-friendly delivery system developed by the Unit for Drug Research and Development at the North-West University, Potchefstroom Campus, South Africa. The skin is the body’s first line of defence against noxious external stimuli. It is considered the largest organ in the body with an intensive and complex structure. It consists of five layers with the first outer layer, the stratum corneum, the most impermeable (Williams, 2003:1). The stratum corneum has excellent barrier function characteristics and is the cause for the time delay in the transdermal delivery of active pharmaceutical ingredients (API) (Barry, 2007:569). Local anaesthetics need to penetrate all the epidermal skin layers in order to reach their target site, the dermis. Skin appendages as well as blood vessels and skin nerve endings are located in the dermis. Local anaesthetics have to reach the free nerve endings in the dermis in order to cause a reversible block on these nerves for a local anaesthetic effect (Richards & McConachie, 1995:41). Penetration enhancement strategies for the transdermal delivery of lidocaine and prilocaine have been investigated and include methods like liposomal entrapment (Franz-Montan et al., 2010; Müller et al., 2004), micellisation (Scherlund et al., 2000), occlusive dressing (Astra Zeneca, 2006), heating techniques (Masud et al., 2010) and iontophoresis (Brounéus et al., 2000). The Pheroid™ delivery system has improved the transdermal delivery of several compounds with its enhanced entrapment capabilities. Pheroid™ consists mainly of unsaturated essential fatty-acids, non-harmful substances that are easily recognised by the body (Grobler et al., 2008:285). The morphology and size of Pheroid™ is easily manipulated because it is a submicron emulsion type formulation which provides it with a vast flexibility profile (Grobler et al., 2008:284). Vesicular entrapment was used to entrap lidocaine HCl and prilocaine HCl in the Pheroid™ and incorporated into an emulgel formulation. An emulgel without the inclusion of Pheroid™ was formulated for comparison with the Pheroid™ emulgel as well as with a hydrogel. Pheroid™ solution was prepared and compared to a phosphate buffer solution (PBS) without Pheroid™, both containing lidocaine HCl and prilocaine HCl as APIs. Franz cell type transdermal diffusion studies were performed on the four semi-solid formulations (emulgel, Pheroid™ emulgel, hydrogel and the commercial product) and two solutions (PBS and Pheroid™). The diffusion studies were performed over a 12 h period followed by the tape stripping of the skin after each diffusion study. Caucasian female abdominal skin was obtained with consent from the donors. The skin for the diffusion cells were prepared by using a Zimmer Dermatome®. PBS (pH 7.4) was prepared as the receptor phase of the diffusion studies. The receptor phase was extracted at certain pre-determined time intervals and analysed with high performance liquid chromatography (HPLC) to determine the amount of API that had traversed the skin. Stratum corneum-epidermis samples and epidermis-dermis samples were prepared and left over night at 4 °C and analysed the next day with HPLC. This was done to determine the amount of API that accumulated in the epidermis-dermis and the amount of API that were left on the outer skin layers (stratum corneum-epidermis). The results from the Franz cell diffusion studies indicated that the emulgel formulation without Pheroid™ shortened the lag time of lidocaine HCl and that the emulgel formulated with Pheroid™ shortened the lag time of prilocaine HCl, when compared to the commercial product. Pheroid™ did not enhance the flux of lidocaine HCl and prilocaine HCl into the skin. The hydrogel formulation demonstrated a high transdermal flux of prilocaine HCl due to the hydrating effect it had on the stratum corneum. The commercial product yielded high flux values for both APIs but it did not result in a high concentration of the APIs delivered to the epidermis-dermis. Pheroid™ technology did, however, enhance the epidermal-dermal delivery of lidocaine HCl and prilocaine HCl into the skin epidermis-dermis. The stability of the emulgel formulation, Pheroid™ emulgel formulation and the hydrogel formulation was examined over a 6 month period. The formulations were stored at 25 °C/60% RH, 30 °C/60% RH and 40 °C/75% RH. The API concentration, mass, pH, zeta potential, particle size, viscosity and visual appearance for each formulation at the different storage conditions were noted and compared at month 0, 1, 2, 3 and 6 to determine if the formulations remained stable for 6 months. The results obtained from the stability study demonstrated that none of the formulations were stable for 6 months. The emulgel remained stable for the first 3 months. At 6 months, large decreases in API concentration and pH occurred which could cause a loss of anaesthetic action in the formulations. The Pheroid™ emulgel formulation did not remain stable for 6 months. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

The aim of this study was to investigate the effect of different penetration enhancers containing essential fatty acids (EFAs) on the transdermal delivery of flurbiprofen. Flurbiprofen was used as a marker / model compound. Fatty acids were chosen as penetration enhancers for their ability to reversibly increase skin permeability through entering the lipid bilayers and disrupting their ordered domains. Fatty acids are natural, non-toxic compounds (Karande & Mitragotri, 2009:2364). Evening primrose oil, vitamin F and Pheroid™ technology all contain fatty acids and were compared using a cream based-formulation. This selection was to ascertain whether EFAs exclusively, or EFAs in a delivery system, would have a significant increase in the transdermal delivery of a compound. For an active pharmaceutical ingredient (API) to be effectively delivered transdermally, it has to be soluble in lipophilic, as well as hydrophilic mediums (Naik et al., 2000:319; Swart et al., 2005:72). This is due to the intricate structure of the skin, where the stratum corneum (outermost layer) is the primary barrier, which regulates skin transport (Barry, 2001:102; Moser et al., 2001:103; Venus et al., 2010:469). Flurbiprofen is highly lipophilic (log P = 4.24) with poor aqueous solubility. It has a molecular weight lower than 500 g/mol indicating that skin permeation may be possible, though the high log P indicates that some difficulty is to be expected (Dollery, 1999:F126; Hadgraft, 2004:292; Swart et al., 2005:72; Karande & Mitragotri, 2009:2363; Drugbank, 2012). In vitro transdermal diffusion studies (utilising vertical Franz diffusion cells) were conducted, using donated abdominal skin from Caucasian females. The studies were conducted over 12 h with extractions of the receptor phase every 2 h to ensure sink conditions. Prior to skin diffusion studies, membrane release studies were performed to determine whether the API was released from the formulation. Membrane release studies were conducted over 6 h and extractions done hourly. Tape stripping experiments were performed on the skin circles after 12 h diffusion studies to determine the concentration flurbiprofen present in the stratum corneum and dermisepidermis. The flurbiprofen concentrations present in the samples were determined using high performance chromatography and a validated method. Membrane release results indicated the following rank order for flurbiprofen from the different formulations: vitamin F > control > evening primrose oil (EPO) >> Pheroid™. The control formulation contained only flurbiprofen and no penetration enhancers. Skin diffusion results on the other hand, indicated that flurbiprofen was present in the stratum corneum and the dermisepidermis. The concentration flurbiprofen present in the receptor phase of the Franz cells (representing human blood) followed the subsequent rank order: EPO > control > vitamin F >> Pheroid™. All the formulations stipulated a lag time shorter than that of the control formulation (1.74 h), with the EPO formulation depicting the shortest (1.36 h). The control formulation presented the highest flux (8.41 μg/cm2.h), with the EPO formulation following the closest (8.12 μg/cm2.h). It could thus be concluded that fatty acids exclusively, rather than in a delivery system, had a significant increase in the transdermal delivery of flurbiprofen. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.