Preformulation studies of two naturally occurring compounds, sulforaphane and myricetin, are presented. Both compounds have shown promise as chemoprevention agents throughout the literature. Despite this evidence, minimal information is available to guide the progression of formulations designed for future drug development. The presented work describes solubility, stability, and solid-state characterization of these compounds. Additionally, a mathematical model based on the ideal solubility equation, which reasonably estimates the solubility of a hydrate is described. This model accounts for the dehydration energetics of the solute as it transforms from hydrate to anhydrous prior to melting and conversion to a hypothetical super-cooled liquid (HSL). This model will lend itself to the appreciation of the solubility differences that can exist between hydrate and anhydrous drug forms. By improving the accuracy of solubility estimation, drug development studies involving hydrates can be designed more accurately.

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.

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.

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.

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.

Thesis (M.S.)--University of Michigan, 1987.

Thesis (M.S.)--University of Michigan, 1984.

Thesis (M.S.)--University of Michigan, 1986.

Thesis (M.S.)--University of Michigan, 1985.

Thesis (M.S.)--University of Michigan, 1988.