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

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

Acne is an extremely common condition, affecting almost 80% of adolescents and young adults. It is an inflammatory disease, characterised by comedones, papules, pustules and sometimes cysts. Factors causing acne include enhanced sebum excretion, hypercornification of the sebaceous duct, ductal coloniazation with Propionibacterium acnes and production of inflammation (Gollnick & Cunliffe, 2003:1). Because of the widespread use of topically applied antimicrobial agents in the treatment of inflammatory acne, resistance of disease-related micro-organisms developed. Therefore new strategies for the treatment of moderate inflammatory acne are necessary. Nicotinamide is a new approach to topical treatment of moderate inflammatory acne without the development of resistant micro-organisms (Otte et al., 2005:257). Using the skin as an alternative route for the administration of nicotinamide for the treatment of acne, may be beneficial. When nicotinamide permeates through the skin, it is directly delivered to the dermis, the place where action is needed and better results can thus be expected after the treatment has started. Another benefit is that smaller amounts of the drug are absorbed systemically with decreased adverse reactions. Unfortunately, using the skin as an alternative route for administering drugs (transdermal drug delivery), has numerous limitations. One of these limitations is the barrier function of the skin (Naik et al., 2000:319). Because of the skin's outstanding ability to protect the body against unwanted substances from its surroundings, it is necessary to use methods to enhance drug penetration through the skin. A new technology, named Pheroid™ technology, was used in this study to enhance penetration through the skin. This technology is based on the use of vesicular structures with no phospholipids or cholesterol to enhance penetration (Grobler et al., 2008:283). The aim of this study was to formulate four different semi-solid formulations with nicotinamide as the active ingredient, and to determine which of the formulations deliver nicotinamide best to the target site. Stability tests over a six months period were also performed on the different formulations. A 3% nicotinamide cream, with and without Pheroid™ vesicles, and a 3% nicotinamide gel, with and without Pheroid™ vesicles, were formulated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

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

Acne is an extremely common condition, affecting almost 80% of adolescents and young adults. It is an inflammatory disease, characterised by comedones, papules, pustules and sometimes cysts. Factors causing acne include enhanced sebum excretion, hypercornification of the sebaceous duct, ductal coloniazation with Propionibacterium acnes and production of inflammation (Gollnick & Cunliffe, 2003:1). Because of the widespread use of topically applied antimicrobial agents in the treatment of inflammatory acne, resistance of disease-related micro-organisms developed. Therefore new strategies for the treatment of moderate inflammatory acne are necessary. Nicotinamide is a new approach to topical treatment of moderate inflammatory acne without the development of resistant micro-organisms (Otte et al., 2005:257). Using the skin as an alternative route for the administration of nicotinamide for the treatment of acne, may be beneficial. When nicotinamide permeates through the skin, it is directly delivered to the dermis, the place where action is needed and better results can thus be expected after the treatment has started. Another benefit is that smaller amounts of the drug are absorbed systemically with decreased adverse reactions. Unfortunately, using the skin as an alternative route for administering drugs (transdermal drug delivery), has numerous limitations. One of these limitations is the barrier function of the skin (Naik et al., 2000:319). Because of the skin's outstanding ability to protect the body against unwanted substances from its surroundings, it is necessary to use methods to enhance drug penetration through the skin. A new technology, named Pheroid™ technology, was used in this study to enhance penetration through the skin. This technology is based on the use of vesicular structures with no phospholipids or cholesterol to enhance penetration (Grobler et al., 2008:283). The aim of this study was to formulate four different semi-solid formulations with nicotinamide as the active ingredient, and to determine which of the formulations deliver nicotinamide best to the target site. Stability tests over a six months period were also performed on the different formulations. A 3% nicotinamide cream, with and without Pheroid™ vesicles, and a 3% nicotinamide gel, with and without Pheroid™ vesicles, were formulated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

The aim of this study was to investigate in vitro transdermal diffusion of a small peptide namely arginine vasopressin (AVP) with the aid of the novel PheroidTM drug delivery system. Generally, peptides seem unfit for transdermal permeation, but it was thought prudent to explore the suitability of this lipid-based system after success was achieved with entrapment of tuberculostatics, bacteria and viruses. Bestatin (a selective aminopeptidase inhibitor) was employed to circumvent any skin-related degradation of the active. Therefore, the effect of bestatin on the preservation of AVP during diffusion was investigated. Vertical Franz cell diffusion studies were conducted with female abdominal skin, with AVP at a concentration of 150 pglml in the donor phase and Hepes buffer as the receptor phase over a twelve-hour period. To prove entrapment of AVP within the lipid structures of the PheroidsTM, fluorescentlylabelled samples were monitored by means of confocal laser scanning microscopy (CLSM), which revealed definite entrapment. In vitro permeation profiles for AVP exhibited a biphasic character, with the majority of permeation occurring during the first two hours. The PheroidTM delivery system proved to be advantageous when applied as delivery medium. The inclusion of bestatin has an enhancing effect on permeation probably due to its protection of AVP. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

The aim of this study was to investigate in vitro transdermal diffusion of a small peptide namely arginine vasopressin (AVP) with the aid of the novel PheroidTM drug delivery system. Generally, peptides seem unfit for transdermal permeation, but it was thought prudent to explore the suitability of this lipid-based system after success was achieved with entrapment of tuberculostatics, bacteria and viruses. Bestatin (a selective aminopeptidase inhibitor) was employed to circumvent any skin-related degradation of the active. Therefore, the effect of bestatin on the preservation of AVP during diffusion was investigated. Vertical Franz cell diffusion studies were conducted with female abdominal skin, with AVP at a concentration of 150 pglml in the donor phase and Hepes buffer as the receptor phase over a twelve-hour period. To prove entrapment of AVP within the lipid structures of the PheroidsTM, fluorescentlylabelled samples were monitored by means of confocal laser scanning microscopy (CLSM), which revealed definite entrapment. In vitro permeation profiles for AVP exhibited a biphasic character, with the majority of permeation occurring during the first two hours. The PheroidTM delivery system proved to be advantageous when applied as delivery medium. The inclusion of bestatin has an enhancing effect on permeation probably due to its protection of AVP. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

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 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.