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.

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.

Acne is a multifactorial skin disease affecting about 80 % of people aged 11 to 30. Several systemic and topical treatments are used to treat existing lesions, prevent scarring and suppress the development of new lesions. Topical therapy is often used as first line treatment for acne, due to the location of the target organ, the pilosebaceous unit, in the skin. Retinoids are widely used as oral or topical treatment for this disease, with tretinoin and adapalene being two of the most used topical retinoids. The transdermal route offers several challenges to drug delivery, e.g. the excellent resistance of the stratum corneum to diffusion, as well as variable skin properties such as site, age, race and disease. Some additional difficulties are associated with the dermatological delivery of tretinoin and adapalene, which include suboptimal water solubility of the retinoids, isomerisation of tretinoin in the skin, mild to severe skin irritation, as well as oxidation and photo–isomerisation of tretinoin, even before crossing the stratum corneum. Researchers constantly strive to improve dermatological retinoid formulations in order to combat low dermal flux, skin irritation and instability. The release kinetics of tretinoin varies greatly according to the way in which it is incorporated into the formulation and according to the type of formulation used. Little research has been conducted regarding improved formulations for adapalene. Pheroid technology is a patented delivery system employed in this study in order to improve the dermal delivery of retinoids. Tretinoin and adapalene were separately incorporated into castor oil, vitamin F and Pheroid creams. The creams were evaluated in terms of their in vitro retinoid release, in vitro transdermal diffusion and stability. Castor oil and Pheroid creams were superior in terms of release and dermal delivery of adapalene. Tretinoin was best released and delivered to the dermis by castor oil cream. The castor oil creams were the most stable formulations, whereas the Pheroid creams were the most unstable. In terms of release, dermal diffusion and stability, castor oil cream proved to be the most suitable cream for both tretinoin and adapalene. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

Acne is a multifactorial skin disease affecting about 80 % of people aged 11 to 30. Several systemic and topical treatments are used to treat existing lesions, prevent scarring and suppress the development of new lesions. Topical therapy is often used as first line treatment for acne, due to the location of the target organ, the pilosebaceous unit, in the skin. Retinoids are widely used as oral or topical treatment for this disease, with tretinoin and adapalene being two of the most used topical retinoids. The transdermal route offers several challenges to drug delivery, e.g. the excellent resistance of the stratum corneum to diffusion, as well as variable skin properties such as site, age, race and disease. Some additional difficulties are associated with the dermatological delivery of tretinoin and adapalene, which include suboptimal water solubility of the retinoids, isomerisation of tretinoin in the skin, mild to severe skin irritation, as well as oxidation and photo–isomerisation of tretinoin, even before crossing the stratum corneum. Researchers constantly strive to improve dermatological retinoid formulations in order to combat low dermal flux, skin irritation and instability. The release kinetics of tretinoin varies greatly according to the way in which it is incorporated into the formulation and according to the type of formulation used. Little research has been conducted regarding improved formulations for adapalene. Pheroid technology is a patented delivery system employed in this study in order to improve the dermal delivery of retinoids. Tretinoin and adapalene were separately incorporated into castor oil, vitamin F and Pheroid creams. The creams were evaluated in terms of their in vitro retinoid release, in vitro transdermal diffusion and stability. Castor oil and Pheroid creams were superior in terms of release and dermal delivery of adapalene. Tretinoin was best released and delivered to the dermis by castor oil cream. The castor oil creams were the most stable formulations, whereas the Pheroid creams were the most unstable. In terms of release, dermal diffusion and stability, castor oil cream proved to be the most suitable cream for both tretinoin and adapalene. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.