Most individuals are influenced by pain at some stage in their lives. It can either be of acute or chronic nature. An acute pain condition initiates and is treated within a time span of 12 weeks. Chronic pain can, however, take substantially longer to treat. Chronic pain may last up to 6 months after the original injury was sustained. The after effects of chronic pain can, however, take years to heal, but physical and emotional scars may even last much longer than the initial chronic ailment. In this study the skin was chosen as an area for delivery of non-steroidal anti-inflammatory drugs for the treatment of pain at the joint and muscle tissue regions. The stratum corneum (the topmost horny layer of the skin), however bars the effective movement of chemical substances across the skin as it forms part of the skin's function to protect the superficial tissue of the body against the external environment. It furthermore plays an important role in regulation of the movement of chemicals across the skin. Sweat pores and hair follicles can be utilised as pathways for the movement of chemical substances through the stratum corneum. Physical deformation ie, hydration of the top layer of the skin, may also enhance the movement of chemicals The non-steroidal anti-inflammatory drug, diclofenac, has been evaluated for transdermal diffusion. Three different diclofenac salts were evaluated, namely diclofenac diethylamine, diclofenac hydroxyethyl pyrrolidine and diclofenac sodium. These salts have the potential to relieve systemic pain conditions. Diclofenac salts, however, possess physicochemical characteristics that are unfavourable for transdermal diffusion. Pheroid™ delivery technology, as patented by the Northwest-University, was implemented as a method to enhance transdermal delivery of the diclofenac salts. During the study each of the diclofenac salts was formulated in a Pheroid™ and non-Pheroid™ formulation. All the formulations as well as corresponding retail products containing similar diclofenac salts were evaluated in order to determine which preparation had the most effective transdermal diffusion. High performance liquid chromatograhphy was implemented in order to determine the concentration of each salt in their various preparations. The Pheroid™ and non-Pheroid™ formulations were also compared to retail products currently available. An active ingredient flux was determined by means of Franz cell diffusion studies. Membrane diffusion studies were utilised in order to determine whether the active ingredients were effectively released from the formulated preparations and market products. Membrane diffusion studies determined that Arthruderm (the retail product containing diclofenac sodium) had the most potential to effectively release the active ingredient from the formulation (median flux 28.36 ± 0.26 ug/cm2.h"1). Franz cell diffusion studies showed no flux values for any of the evaluated preparations, including the retail products. Concentrations obtained within the epidermis and dermis were determined through tape stripping of these areas. The largest concentration of active ingredient within the epidermis was obtained from the studies done on Voltaren® (the retail product containing diclofenac diethylamine) which was 7.27 |ig/cm2.h"1 the largest value in the dermis was obtained from a non-Pheroid™ formulation containing diclofenac sodium (4.47 ug/ml). Confocal laser scanning microscopy was utilised and the micrographs where evaluated to ensure that the diclofenac salts were effectively entrapped in the Pheroid™ delivery system. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne is a common disease characterised by follicular hyperkeratinisation, bacterial hipercolonisation as well as immune reactions and inflammation. In acne, reactive oxygen species (ROS) may be released from the damaged follicular walls, which could cause the advancement of inflammation in the pathogenesis of the disease. The topical application of antioxidants is a promising approach to support the endogenous antioxidant defence and avoid oxidative injury that may lead to acne. The skin provides a painless and patient-friendly approach for systemic drug administration. Transdermal drug delivery not only improves patient compliance, but also avoids the first-pass effect. The major hurdle to penetration of matter through the skin is provided by an outward layer of the skin, the stratum corneurm (SC). Overcoming this barrier safely and reversibly is a fundamental problem in the field of transdermal drug delivery. Alpha-lipoic acid was utilised as the cosmeceutical active and can be classified in a mixed category of compounds that lie between cosmetics and drugs. Alpha-lipoic acid and its reduced form, dihydrolipoic acid, have been described as the "universal antioxidants" because of their capacity to quench a number of free radicals in both aqueous and lipid environments, their metal-chelating properties and ability to restore other antioxidants from their inactive form. The Pheriod™ system is a new manner of drug delivery aimed at overcoming the barrier function of the skin. It consists of vesicular structures, the sizes of which vary from 200-440 nm. These vesicles, prepared from customised essential fatty acids, were found to advance the efficacy of topically administered compounds. The aim of this study was to determine whether the Pheroid™ delivery system would enhance the transdermal delivery of formulations containing alpha-lipoic acid to the target site by performing Franz cell diffusion studies over a 12 hour period, followed by tape-stripping experiments. The results of the formulations containing Pheroid™ were compared to those of the formulations without Pheroid™. Experimental determination of transdermal flux of the alpha-lipoic acid formulations revealed that Pheroid™ improved the transdermal delivery of alpha-lipoic acid. The average flux of Pheroid™ cream from 0 to 2 hours wass 58.01 ± 6.63 ug/cm2.h. The average flux of Pheroid™ gel from 4 to 12 hours was 22.18 ± 3.33 ug/cm2.h. Tape-stripping experiments proved that the concentrations of alpha-lipoic acid in Pheroid™ cream and cream that remained in the epidermis after application to the skin were 569.10 ug/ml and 764.93 ug/ml respectively. The concentrations of alpha-lipoic acid in Pheroid gel and gel that diffused into the dermis were 23.62 ug/ml and 61.06 ug/ml respectively. Aqueous solubility and log D partition coefficient of alpha-lipoic acid were determined. Inspection of the log D value of -0.78 indicated that the compound was unfavourable to penetrate the skin, whereas the aqueous solubility of 8.602 mg/ml in PBS at a temperature of 32 °C indicated favourable penetration. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne affects as many as 80% of young adults and adolescents all over the world. This detrimental condition can be classified into four stages: (a) open comedo (blackhead), (b) closed comedo (whitehead), (c) papule and (d) pustule (Russell, 2000:357-366). There are various factors that can lead to acne outbreaks which include: (a) hormone level changes during the menstrual cycle in women, (b) certain drugs (i.e. lithium), (c) certain cosmetics and (d) environmental conditions such as humidity (University of Maryland, 2009:1). The skin performs a variety of functions which include the two major functions: (a) the containment and (b) the protection of the internal organs of the body. The containment function relates specifically to the ability of the skin to confine the underlying tissues and restrain their movement from place to place. The protective function, on the other hand, relates to the ability of the skin to act as a microbiological barrier to most micro-organisms; a chemical barrier to exogenous chemical compounds; barrier to radiation and electrical shock; and mechanical barrier to impact (Danckwerts, 1991:315). Niacinamide and salicylic acid were chosen in combination, due to the beneficial effects that they have on acne. Niacinamide has an anti-inflammatory action on acne; which reduces redness, dryness and irritation caused by Propioni-bacterium acnes that live in the clogged pores of pimples (Acnetreatmentlab, 2008:1). Salicylic acid is a keratolytic and keratoplastic agent. It is used in combination with other ingredients to enhance the shedding of corneocytes. This causes penetration into the skin to be very difficult (SAMF, 2005:177). The solubility of niacinamide and salicylic acid in PBS (pH 7.4 at 32°C) were 212.95 mg/ml and 4.07 mg/ml, respectively. The log D values of niacinamide and salicylic acid were determined to be -0.32 and 0.33, respectively. According to the solubility of niacinamide and salicylic acid it was expected that both of the active ingredients would permeate through the skin. However, it is expected that niacinamide will depict enhanced permeation with respect to salicylic acid. The results of the log D for both of the active ingredients indicate that there would not be optimal permeation. This study involved the formulation of four different acne preparations (Pheroid™cream, Pheroid™gel, cream and gel), combining niacinamide and salicylic acid. The evaluation of stability parameters for the different formulations indicated that none of the formulations was stable under the different storage conditions determined by the Medicines Control Council. Nevertheless, the cream and gel were the most stable of the four formulations. Visual assessment of the Pheroid™ formulations with the confocal laser scanning microscopy (CLMS) was conducted and inconclusive evidence to whether the active substances were entrapped within the Pheroids™, was obtained. Franz cell diffusion studies indicated that the cream (in the case of niacinamide) and gel (in the case of salicylic acid) depicted the highest average and median flux from hours 6 to 12. Results of the tape stripping studies showed that with the gel formulation, concentrations of 2.060 ug/ml and 44.749 ug/ml niacinamide were obtained in the epidermis and dermis respectively. After the Pheroid™ gel was applied, tape stripping depicted only 1.587 ug/ml niacinamide in the epidermis with respect to 22.764 ug/ml niacinamide in the dermis. The cream formulation, on the other hand, showed niacinamide concentrations of 2.001 ug/ml in the epidermis and 13.363 ug/ml in the dermis, whereas with the Pheroid™ cream formulation, concentrations of 1.097 ug/ml and 18.061 ug/ml were obtained in the epidermis and dermis respectively. Tape stripping results depicted that with the gel formulation, concentrations of 2.113 ug/ml and 49.519 ug/ml salicylic acid were obtained in the epidermis and dermis respectively, whereas the Pheroid™ gel formulation showed salicylic acid, concentrations of 1.114 ug/ml in the epidermis and 95.360 ug/ml in the dermis. The cream formulation, however, depicted salicylic acid concentrations of 0.758 ug/ml in the epidermis and 44.729 ug/ml in the dermis. Lastly, after the Pheroid™ cream was applied, salicylic acid concentrations of 0.411 ug/ml and 48.424 ug/ml in the epidermis and dermis respectively, were measured. It could, therefore, be concluded that both niacinamide and salicylic acid tend to concentrate more in the dermis, irrespective of the formulation. This may be an advantage since acne is usually targeted in the dermis and epidermis. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne is a common skin disease that affects the follicular unit of the skin. Inflammatory- and noninflammatory forms of acne exist. The most affected areas on the body include the face, upper part of the chest and the back. These are the areas with the most sebaceous follicles. Acne occurs when hyperkeratinisation causes the cells of the hair follicle to shed too fast. These cells then block the follicle opening. Thus, sebum cannot pass through the hair follicle onto the skin. The human skin is composed of three layers, namely the epidermis, which acts as a waterproof layer and a barrier to infections; the dermis, which contains the skin appendages; and the subcutaneous fat layer. Skin acts as a protective layer against pathogens and damage to the body. It also provides a semi-impermeable barrier to prevent water loss. Azelaic acid and niacinamide are both currently used in the treatment of acne. Azelaic acid is a saturated dicarboxylic acid which is used to treat mild to moderate acne. It has antibacterial, keratolytic and comedolytic properties. Niacinamide, on the other hand, is the amide of nicotinic acid and is beneficial in the treatment of both papular and pustular acne. It has a demonstrated anti-inflammatory action and causes dose-dependent inhibition of sebocyte secretions. The Pheroid™ delivery system is a colloidal system that consists of even lipid-based submicron-and micron-sized structures that are very unique in nature. This technology is able to improve the absorption and/or efficacy of various active ingredients, as well as other compounds. In this study, a cream, Pheroid™ cream, a gel and a Pheroid™ gel were formulated, containing both azelaic acid and niacinamide. Stability tests were conducted on these formulations for six months, and it was established that none of the formulations were stable under the different storage conditions. Tests that were conducted during stability testing, as determined by the Medicines Control Council, included: assay, mass variation, appearance, viscosity, pH determination and confocal laser scanning microscopy (CLSM). Diffusion studies (12 hours long in total) with vertical Franz cells were conducted with Caucasian female skin obtained after abdominoplastic surgery. Tape-stripping followed in order to establish the epidermis and dermis concentrations of azelaic acid and niacinamide. Significant concentrations of both active ingredients were found in the epidermis and the dermis after 12 hours. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

The aim of this in vitro study was to investigate the efficacy of the novel Pheroid™ technology system in a semi-solid dosage form, for the topical delivery of acyclovir (5% w/w), an anti-viral agent and ketoconazole (2% w/w) an anti-fungal agent. The human immununodeficiency virus (HIV) had an immense impact on the spectrum of diagnosis of cutaneous diseases since its first manifestation in the late 1970's (Yen-More et al., 2000:432). The skin is the most commonly affected organ in HIV infected individuals with skin manifestations present in up to 92% of HIV-positive patients. According to Ramdial (2000:113) the skin may also be the first or the only organ affected throughout the course of the HIV/AIDS disease. HIV/AIDS patients are more susceptible to infections due to their compromised immune systems (Durden & Elewski, 1997:200) and an exceptionally wide range of infectious skin manifestations presents in HIV/AIDS infected individuals, some of which are viral and fungal. Acyclovir is an anti-viral active against herpes simplex virus type 1 and type 2, varicella-zoster virus, Epstein-Barr virus and the cytomegalovirus (Hayden, 2001:1317). The anti-fungal drug, ketoconazole has activity against the majority of pathogenic fungi which include Candida species and Histoplasma capsulatum (Bennett, 2001:1301). It is appropriate to formulate a topical product containing both acyclovir and ketoconazole because viral and fungal cutaneous manifestations are regularly encountered in combination in HIV/AIDS infected individuals,. This combination topical product may be useful in the treatment of viral and fungal opportunistic skin manifestations. Curing these skin lesions may also assist to improve the state of mind and wellbeing of infected individuals. The skin, however, acts as a barrier against diffusion of substances through the underlying tissue. The main problem in transdermal and dermal delivery of actives is to overcome the stratum corneum, the skin's natural barrier (Menon, 2002:4). The Pheroid™ delivery system can promote the absorption and increase the efficacy of a selection of active ingredients in dermatological preparations (Grobler et al., 2008:284). The aim of this study was to formulate a stable semi-solid product containing Pheroid™ to determine whether Pheroid™ technology would enhance the flux and/or delivery of acyclovir and ketoconazole to the epidermal and dermal layers of the skin. In vitro studies and tape stripping were used to determine the effect that the Pheroid™ delivery system had on skin permeation of acyclovir and ketoconazole in semi-solid formulations. The formulae containing no Pheroid™ were used as a control against which the efficacy of the formulations containing Pheroid™ was measured. The stability of the formulated semi-solid products was examined over a period of 6 months according to the International Conference of Harmonisation (ICH) Tripartite Guidelines (2003) and the Medicines control council (MCC) of South Africa (2006). The formulated products were stored at three different temperatures. The stability tests included the assay of the actives and other attributes in the formulation, pH, viscosity, mass loss and particle size observation. These tests were conducted at 0, 1, 2, 3 and 6 months. The results demonstrated that the transdermal flux, epidermal and dermal penetration of acyclovir was enhanced by the Pheroid™ cream formulation. Ketoconazole's transdermal flux as well as delivery to the epidermal and dermal layers of the skin was improved by the Pheroid™ emulgel formula. The topical delivery of ketoconazole and acyclovir was thus enhanced by Pheroid™ technology. The Pheroid™ formulations, however, did not meet the requirements for stability according to the ICH and MCC. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Since its initial discovery in 1922 by Banting and Best, the formulation of an oral insulin delivery system has ever been so troublesome. Unfortunately, insulin is indispensable in the treatment of diabetes mellitus, which affects approximately 350 million people worldwide. Various factors contribute to the peptide being such a persistently difficult hormone to be used in an oral formulation. The gastrointestinal tract is home to various protein digestive enzymes such as pepsins in the stomach and trypsin, chymotrypsin and carboxypeptidases in the small intestine, which digests insulin. Also the physical barrier of the gastrointestinal tract, i.e. the columnar epithelial layer which lines the tract, is a tightly bound collection of cells with minimal leakage and is thus a sound barrier for the absorption of peptides and hormones. The aim of this study is to determine whether a dosage form for insulin, entrapped in Pheroid™ vesicles and -micro sponges, can overcome these barriers and successfully deliver insulin at the site of action resulting in a significant therapeutic response. Initial phases of the study consisted of the manufacturing of Pheroid™ vesicles and - microsponges, entrapment of flourescein-isothiocyanate labelled insulin (FITC-insulin) into the Pheroid™. The Pheroid™-insulin complex was analysed with confocal laser scanning microscopy (CLSC) to determine drug loading. In vivo experiment in Sprague - Dawley rats were done where blood glucose levels as well as insulin blood levels were monitored after administration of different Pheroid insulin formulations. Firstly a standard reference was set by subcutaneous injection of insulin (0.5 IU/kg) in rats followed by a comparative study where administration to the stomach, colon and ileum (50.0 IUlkg insulin) were compared by means of blood insulin levels and therapeutic effect between the control and Pheroid™ complexes (Pheroid™ vesicles and microsponges). Each study was done by means of direct injection into the stomach, ileum or colon through which the insulin in saline (control) or insulin-Pheroid™ complex was administered. Nasal administration of 8.0 and 12.0 IU/kg insulin in saline (control) or insulin-Pheroid™ complex was done in the right nostril of Sprague - Dawley rats. Blood samples were taken from the artery carotis communis by means of an inserted cannula. Blood samples were taken just before administration and then at 5, 10, 15, 30, 60, 120 and 180 minutes after administration. Blood glucose levels were measured just after every blood sample was taken and plasma insulin levels were determined with a human insulin specific radioimmunoassay. The results were compared to the reference as well as the control to determine relative bioavailability. Through the results obtained it was discovered that in comparison with the various parts of the or tract, the ileum showed undoubtedly to be the best area of absorption where Pheroid™ vesicles revealed a peak 42.0 % lowering in blood glucose levels after 60 minutes and a peak plasma concentration of 244.0 /uID/ml after 5 minutes together with an 18.7 % lowering in blood glucose levels after just 5 minutes. After nasal administration of Pheroid™ microsponges (8.0 ID/kg insulin) a remarkable lowered blood glucose level of 19.2 % after 10 minutes and 36.5 % after 30 minutes as well as a peak plasma insulin level of220.2 /lID/ml after 3 hours was observed. Insulin entrapped in Pheroid™ microsponges administered at 12.0 ID/kg showed a maximum blood glucose lowering effect of72.4 % after 3 hours with a peak plasma level of 154.8 uID/ml also after 3 hours, thus showing a long acting effect. In conclusion, the delivery system based on Pheroid™ technology shows a sufficient therapeutic effect for insulin and is therefore promising for further in vivo evaluation and ultimately for medicinal use to patients suffering from diabetes mellitus. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

Most individuals are influenced by pain at some stage in their lives. It can either be of acute or chronic nature. An acute pain condition initiates and is treated within a time span of 12 weeks. Chronic pain can, however, take substantially longer to treat. Chronic pain may last up to 6 months after the original injury was sustained. The after effects of chronic pain can, however, take years to heal, but physical and emotional scars may even last much longer than the initial chronic ailment. In this study the skin was chosen as an area for delivery of non-steroidal anti-inflammatory drugs for the treatment of pain at the joint and muscle tissue regions. The stratum corneum (the topmost horny layer of the skin), however bars the effective movement of chemical substances across the skin as it forms part of the skin's function to protect the superficial tissue of the body against the external environment. It furthermore plays an important role in regulation of the movement of chemicals across the skin. Sweat pores and hair follicles can be utilised as pathways for the movement of chemical substances through the stratum corneum. Physical deformation ie, hydration of the top layer of the skin, may also enhance the movement of chemicals The non-steroidal anti-inflammatory drug, diclofenac, has been evaluated for transdermal diffusion. Three different diclofenac salts were evaluated, namely diclofenac diethylamine, diclofenac hydroxyethyl pyrrolidine and diclofenac sodium. These salts have the potential to relieve systemic pain conditions. Diclofenac salts, however, possess physicochemical characteristics that are unfavourable for transdermal diffusion. Pheroid™ delivery technology, as patented by the Northwest-University, was implemented as a method to enhance transdermal delivery of the diclofenac salts. During the study each of the diclofenac salts was formulated in a Pheroid™ and non-Pheroid™ formulation. All the formulations as well as corresponding retail products containing similar diclofenac salts were evaluated in order to determine which preparation had the most effective transdermal diffusion. High performance liquid chromatograhphy was implemented in order to determine the concentration of each salt in their various preparations. The Pheroid™ and non-Pheroid™ formulations were also compared to retail products currently available. An active ingredient flux was determined by means of Franz cell diffusion studies. Membrane diffusion studies were utilised in order to determine whether the active ingredients were effectively released from the formulated preparations and market products. Membrane diffusion studies determined that Arthruderm (the retail product containing diclofenac sodium) had the most potential to effectively release the active ingredient from the formulation (median flux 28.36 ± 0.26 ug/cm2.h"1). Franz cell diffusion studies showed no flux values for any of the evaluated preparations, including the retail products. Concentrations obtained within the epidermis and dermis were determined through tape stripping of these areas. The largest concentration of active ingredient within the epidermis was obtained from the studies done on Voltaren® (the retail product containing diclofenac diethylamine) which was 7.27 |ig/cm2.h"1 the largest value in the dermis was obtained from a non-Pheroid™ formulation containing diclofenac sodium (4.47 ug/ml). Confocal laser scanning microscopy was utilised and the micrographs where evaluated to ensure that the diclofenac salts were effectively entrapped in the Pheroid™ delivery system. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne is a common disease characterised by follicular hyperkeratinisation, bacterial hipercolonisation as well as immune reactions and inflammation. In acne, reactive oxygen species (ROS) may be released from the damaged follicular walls, which could cause the advancement of inflammation in the pathogenesis of the disease. The topical application of antioxidants is a promising approach to support the endogenous antioxidant defence and avoid oxidative injury that may lead to acne. The skin provides a painless and patient-friendly approach for systemic drug administration. Transdermal drug delivery not only improves patient compliance, but also avoids the first-pass effect. The major hurdle to penetration of matter through the skin is provided by an outward layer of the skin, the stratum corneurm (SC). Overcoming this barrier safely and reversibly is a fundamental problem in the field of transdermal drug delivery. Alpha-lipoic acid was utilised as the cosmeceutical active and can be classified in a mixed category of compounds that lie between cosmetics and drugs. Alpha-lipoic acid and its reduced form, dihydrolipoic acid, have been described as the "universal antioxidants" because of their capacity to quench a number of free radicals in both aqueous and lipid environments, their metal-chelating properties and ability to restore other antioxidants from their inactive form. The Pheriod™ system is a new manner of drug delivery aimed at overcoming the barrier function of the skin. It consists of vesicular structures, the sizes of which vary from 200-440 nm. These vesicles, prepared from customised essential fatty acids, were found to advance the efficacy of topically administered compounds. The aim of this study was to determine whether the Pheroid™ delivery system would enhance the transdermal delivery of formulations containing alpha-lipoic acid to the target site by performing Franz cell diffusion studies over a 12 hour period, followed by tape-stripping experiments. The results of the formulations containing Pheroid™ were compared to those of the formulations without Pheroid™. Experimental determination of transdermal flux of the alpha-lipoic acid formulations revealed that Pheroid™ improved the transdermal delivery of alpha-lipoic acid. The average flux of Pheroid™ cream from 0 to 2 hours wass 58.01 ± 6.63 ug/cm2.h. The average flux of Pheroid™ gel from 4 to 12 hours was 22.18 ± 3.33 ug/cm2.h. Tape-stripping experiments proved that the concentrations of alpha-lipoic acid in Pheroid™ cream and cream that remained in the epidermis after application to the skin were 569.10 ug/ml and 764.93 ug/ml respectively. The concentrations of alpha-lipoic acid in Pheroid gel and gel that diffused into the dermis were 23.62 ug/ml and 61.06 ug/ml respectively. Aqueous solubility and log D partition coefficient of alpha-lipoic acid were determined. Inspection of the log D value of -0.78 indicated that the compound was unfavourable to penetrate the skin, whereas the aqueous solubility of 8.602 mg/ml in PBS at a temperature of 32 °C indicated favourable penetration. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne affects as many as 80% of young adults and adolescents all over the world. This detrimental condition can be classified into four stages: (a) open comedo (blackhead), (b) closed comedo (whitehead), (c) papule and (d) pustule (Russell, 2000:357-366). There are various factors that can lead to acne outbreaks which include: (a) hormone level changes during the menstrual cycle in women, (b) certain drugs (i.e. lithium), (c) certain cosmetics and (d) environmental conditions such as humidity (University of Maryland, 2009:1). The skin performs a variety of functions which include the two major functions: (a) the containment and (b) the protection of the internal organs of the body. The containment function relates specifically to the ability of the skin to confine the underlying tissues and restrain their movement from place to place. The protective function, on the other hand, relates to the ability of the skin to act as a microbiological barrier to most micro-organisms; a chemical barrier to exogenous chemical compounds; barrier to radiation and electrical shock; and mechanical barrier to impact (Danckwerts, 1991:315). Niacinamide and salicylic acid were chosen in combination, due to the beneficial effects that they have on acne. Niacinamide has an anti-inflammatory action on acne; which reduces redness, dryness and irritation caused by Propioni-bacterium acnes that live in the clogged pores of pimples (Acnetreatmentlab, 2008:1). Salicylic acid is a keratolytic and keratoplastic agent. It is used in combination with other ingredients to enhance the shedding of corneocytes. This causes penetration into the skin to be very difficult (SAMF, 2005:177). The solubility of niacinamide and salicylic acid in PBS (pH 7.4 at 32°C) were 212.95 mg/ml and 4.07 mg/ml, respectively. The log D values of niacinamide and salicylic acid were determined to be -0.32 and 0.33, respectively. According to the solubility of niacinamide and salicylic acid it was expected that both of the active ingredients would permeate through the skin. However, it is expected that niacinamide will depict enhanced permeation with respect to salicylic acid. The results of the log D for both of the active ingredients indicate that there would not be optimal permeation. This study involved the formulation of four different acne preparations (Pheroid™cream, Pheroid™gel, cream and gel), combining niacinamide and salicylic acid. The evaluation of stability parameters for the different formulations indicated that none of the formulations was stable under the different storage conditions determined by the Medicines Control Council. Nevertheless, the cream and gel were the most stable of the four formulations. Visual assessment of the Pheroid™ formulations with the confocal laser scanning microscopy (CLMS) was conducted and inconclusive evidence to whether the active substances were entrapped within the Pheroids™, was obtained. Franz cell diffusion studies indicated that the cream (in the case of niacinamide) and gel (in the case of salicylic acid) depicted the highest average and median flux from hours 6 to 12. Results of the tape stripping studies showed that with the gel formulation, concentrations of 2.060 ug/ml and 44.749 ug/ml niacinamide were obtained in the epidermis and dermis respectively. After the Pheroid™ gel was applied, tape stripping depicted only 1.587 ug/ml niacinamide in the epidermis with respect to 22.764 ug/ml niacinamide in the dermis. The cream formulation, on the other hand, showed niacinamide concentrations of 2.001 ug/ml in the epidermis and 13.363 ug/ml in the dermis, whereas with the Pheroid™ cream formulation, concentrations of 1.097 ug/ml and 18.061 ug/ml were obtained in the epidermis and dermis respectively. Tape stripping results depicted that with the gel formulation, concentrations of 2.113 ug/ml and 49.519 ug/ml salicylic acid were obtained in the epidermis and dermis respectively, whereas the Pheroid™ gel formulation showed salicylic acid, concentrations of 1.114 ug/ml in the epidermis and 95.360 ug/ml in the dermis. The cream formulation, however, depicted salicylic acid concentrations of 0.758 ug/ml in the epidermis and 44.729 ug/ml in the dermis. Lastly, after the Pheroid™ cream was applied, salicylic acid concentrations of 0.411 ug/ml and 48.424 ug/ml in the epidermis and dermis respectively, were measured. It could, therefore, be concluded that both niacinamide and salicylic acid tend to concentrate more in the dermis, irrespective of the formulation. This may be an advantage since acne is usually targeted in the dermis and epidermis. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne is a common skin disease that affects the follicular unit of the skin. Inflammatory- and noninflammatory forms of acne exist. The most affected areas on the body include the face, upper part of the chest and the back. These are the areas with the most sebaceous follicles. Acne occurs when hyperkeratinisation causes the cells of the hair follicle to shed too fast. These cells then block the follicle opening. Thus, sebum cannot pass through the hair follicle onto the skin. The human skin is composed of three layers, namely the epidermis, which acts as a waterproof layer and a barrier to infections; the dermis, which contains the skin appendages; and the subcutaneous fat layer. Skin acts as a protective layer against pathogens and damage to the body. It also provides a semi-impermeable barrier to prevent water loss. Azelaic acid and niacinamide are both currently used in the treatment of acne. Azelaic acid is a saturated dicarboxylic acid which is used to treat mild to moderate acne. It has antibacterial, keratolytic and comedolytic properties. Niacinamide, on the other hand, is the amide of nicotinic acid and is beneficial in the treatment of both papular and pustular acne. It has a demonstrated anti-inflammatory action and causes dose-dependent inhibition of sebocyte secretions. The Pheroid™ delivery system is a colloidal system that consists of even lipid-based submicron-and micron-sized structures that are very unique in nature. This technology is able to improve the absorption and/or efficacy of various active ingredients, as well as other compounds. In this study, a cream, Pheroid™ cream, a gel and a Pheroid™ gel were formulated, containing both azelaic acid and niacinamide. Stability tests were conducted on these formulations for six months, and it was established that none of the formulations were stable under the different storage conditions. Tests that were conducted during stability testing, as determined by the Medicines Control Council, included: assay, mass variation, appearance, viscosity, pH determination and confocal laser scanning microscopy (CLSM). Diffusion studies (12 hours long in total) with vertical Franz cells were conducted with Caucasian female skin obtained after abdominoplastic surgery. Tape-stripping followed in order to establish the epidermis and dermis concentrations of azelaic acid and niacinamide. Significant concentrations of both active ingredients were found in the epidermis and the dermis after 12 hours. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.