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.

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.

Artemisinins are known for their low aqueous solubility and resultant poor and erratic absorption upon oral administration. The poor solubility and erratic absorption usually translate, to low bibavailability. Enzymatic degradation and physiological barriers are also amongst the challenges which must be overcome to ensure effective delivery. Artemisininbased monotherapy and combination therapies are essential for the management and treatment of uncomplicated as well as cerebral malaria. Artemisone and artemiside are novel artemisinin derivatives, their antimalarial activity/efficacy was evaluated in vitro and in vivo in the presence and absence of Pheroid™ technology. Pheroid™ technology is a patented drug delivery system which has the ability to capture, transport and deliver pharmacologically active compounds. Pharmacokinetic models were also constructed for artemis one and artemiside, both in the presence and absence of Pheroid™ technology. Results obtained with the jn vitro antimalarial activity evaluation indicated that artemiside was slightly more potent than artemisone and much more potent than artesunate. Artemiside had IC50 values of 0.54 ± 0.03 nM (reference) and 0.10 ± 0.05 nM (Pheroid™) (p = 0.009) while artemisone had values of 0.94 ± 0.04 nM (reference) and 0.21 ± 0.04 nM (Pheroid™) (p = 0.0001). Artesunate had IC50 values of 29.65 ± 0.05 nM (reference) and 10.20 ± 0.04 nM (Pheroid™) (p < 0.0001). Results obtained with the in vivo antimalarial activity evaluation indicated that artemisone led to more favourable treatment outcomes than artemiside. The Peters' 4-day suppressive test was used as a basis model. With artemisone treatment recrudescence occured at 16 days post infection at a dose of 20.0 mg/kg bodyweight and at 12 days post infection at 2.5 mg/kg bodyweight. With artemiside recrudescence occurred at 8 days post infection with both the 10.0 mg/kg and 2.5 mg/kg bodyweight treatment regimens. When comparing the antimalarial effect of the drugs with and without Pheroid™ technology there was no significant difference in terms of parasite reduction or in the achieved treatment outcomes of either compounds. The pharmacokinetic parameters were evaluated in a mouse model where C57 BL6 mice were used. The compounds were administered at a dose of 50.0 mg/kg bodyweight via an oral gavage tube at a volume of 200 µl. Blood samples were collected by means of tail bleeding. Sensitive and selective LC/MS/MS methods were developed to analyze the drug concentrations in the plasma samples. The relative bioavailability of artemisone was RA = 1.0 (reference) and RA = 4.57 (Pheroid™) (p < 0.001). The absolute bioavailability was calculated as F = 0.10 (reference) and F = 0.48(Pheroid™) (p < 0.001). The boiavailability of artemiside was not dramatically enhanced by the Pheroid™ delivery system. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

The Plasmodium falciparum parasite, carried by Anopheles mosquitoes, is currently a global problem due to the rising incidence of resistance of the parasite to available antimalaria drugs. Resistance and difficult treatment groups, including pregnant woman and young children, are pressing for the development of new, safe and effective prophylactic and treatment antimalarials. Because of the extensive process of developing new drugs, researchers and health care professionals have turned to combination therapy where a fast acting antimalarial is combined with slower acting drugs, such as antibiotics. The macrolide antibiotics, erytbromycin and azithromycin, have been studied to a limited extent for their potential antimalarial effect. Certain advantages, such as their safety profile (especially that of azithromycin) in pregnancy and administration to young children, motivates continual research into the advancement of the effect these drugs exude on malaria. Drug delivery systems contribute to the efficacy of medicines, conquering several difficulties of treatment with oral medication. Pheroid™ technology is a patented drug delivery system, mainly consisting of plant and essential fatty acids, and has been demonstrated to entrap, carry and deliver pharmacologically active compounds and other useful molecules. This study compared the in vitro effects of the macrolide antibiotics on the growth of a chloroquine-resistant strain (RSA 11) of Plasmodium falciparum to the effects of the macrolides entrapped in Pheroid™ vesicles on the same strain over and extended observation period of 144 hours. ELISA assays were conducted by analysing the HRP II (histidine-rich protein) levels on a pre-coated microtitre plate. The effects of the type of formulation, concentration and time were compared. The in vitro difference between erythromycin alone and entrapped in Pheroid™ vesicles were found to be statistically significant (p = 0.000000) while the effects of both formulations did not seem to be concentration dependant (p = 0.628424). Prolonged exposure was also statistically meaningful (p = 0.008268), though it seems that exposure need not exceed 96 hours. The type of formulation, in the case of azithromycin (azithromycin alone vs. azitbromycin entrapped in Pheroid™ vesicles), proved statistically significant (P = 0.002572), while neither formulation seemed concentration dependant (P = 0.427731). Prolonged exposure was found to be statistically insignificant for azithromycin (P = 0.221941). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Stability plays an important role in the development of a new drug product. High Performance Liquid Chromatography (HPLC) is considered a stability indicating method of analysis. It is widely used in the pharmaceutical industry for the quantification of small organic molecules during stability testing. Previous stability studies conducted on Pheroid™-based drug products, experienced problems with the generation of reliable data by means of HPLC analysis. With these studies it was concluded that the inconclusive results could either be attributed to the stability of the delivery system itself and the compatibility of the active pharmaceutical ingredients (API's) with the delivery system, or to the usage of unsuitable HPLC methods. The aims of this study were to: i. determine if the Pheroid™ delivery system changes significantly over time at accelerated storage conditions and how these changes influence the HPLC analysis, ii. determine the effect of the anti-oxidant tert-butylhydroquinone (TBHQ) on the stability and HPLC analysis of the Pheroid™ delivery system, and iii. to suggest a suitable approach for the analysis of Pheroid™-based drug products. Pheroid™ microsponges, containing no API's, were prepared and stored for a period of three months at 5°C, 25°C+60%RH, 30°C+65%RH and 40°C+75%RH. Two of the four Pheroid™ formulations contained an extra anti-oxidant, namely TBHQ. Monthly HPLC analyses were done using existing methods for mefloquine and artesunate. In addition to HPLC analysis, particle size analysis and Confocal Laser Scanning Microscopy (CLSM) were undertaken to support the HPLC results and provide information concerning the overall stability of the Pheroid™ delivery system. After the completion of the above analyses, experiments were carried out to determine whether adjustments to some of the key chromatographic parameters could improve the separation of Pheroid™-based samples. The parameters that were subjected to change included the organic solvent, isocratic versus gradient separation, pH and detection wavelength. Two pro-Pheroid vesicles formulations were prepared and stored for a three month period at 40°C+75%RH only. No API was added to the one formulation while the other contained 2 mg/ml of mefloquine hydrochloride. Results obtained indicated that the Pheroid™ formulations changed after exposure to elevated temperature and humidity. The number of detectable peaks increased, longer run times became necessary and solubility in the sample solvent (methanol) decreased. Solubility of the Pheroid™ formulations in methanol was preserved to some extent by the presence of TBHQ. Physical signs of instability like discolouration and creaming were noted for TBHQ-containing formulations. TBHQ also seemed to have influenced the particle sizes, particle size distributions and structure of the Pheroid™ microsponges. With adjustments made to the HPLC method it was found that: i. the sample solvent is incompatible with the HPLC system, ii. very hydrophobic compounds are present in the Pheroid™-based samples, iii. acetontrile and methanol are unsuitable for both gradient and isocratic separation of Pheroid™-based samples, iv. more Pheroid™ components absorb at shorter wavelengths, and v. small changes in the pH values usually implemented do not influence the retention and selectivity of the Pheroid™ components. The Pheroid™ delivery system proved to be too complex and reversed hydrophobic for phase HPLC analysis. Preparation of the sample by only diluting the Pheroid™ formulations with pure methanol was not optimal. These samples introduced compounds to the column of which some caused interferences with the analyte peak while others were difficult to elute from the column. To continue using HPLC for the analysis of Pheroid™-based drug products, it is therefore recommended that attention should be given to the development of a more appropriate sample preparation procedure, like solid phase extraction or liquid-liquid extraction, one that will eliminate the effects of the Pheroid™ components. Physical instabilities noticed with the addition of TBHQ, suggest that there should also be attended to the compatibility and stability of each of the components in the Pheroid™ delivery system during formulation development. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Artemisinins are known for their low aqueous solubility and resultant poor and erratic absorption upon oral administration. The poor solubility and erratic absorption usually translate, to low bibavailability. Enzymatic degradation and physiological barriers are also amongst the challenges which must be overcome to ensure effective delivery. Artemisininbased monotherapy and combination therapies are essential for the management and treatment of uncomplicated as well as cerebral malaria. Artemisone and artemiside are novel artemisinin derivatives, their antimalarial activity/efficacy was evaluated in vitro and in vivo in the presence and absence of Pheroid™ technology. Pheroid™ technology is a patented drug delivery system which has the ability to capture, transport and deliver pharmacologically active compounds. Pharmacokinetic models were also constructed for artemis one and artemiside, both in the presence and absence of Pheroid™ technology. Results obtained with the jn vitro antimalarial activity evaluation indicated that artemiside was slightly more potent than artemisone and much more potent than artesunate. Artemiside had IC50 values of 0.54 ± 0.03 nM (reference) and 0.10 ± 0.05 nM (Pheroid™) (p = 0.009) while artemisone had values of 0.94 ± 0.04 nM (reference) and 0.21 ± 0.04 nM (Pheroid™) (p = 0.0001). Artesunate had IC50 values of 29.65 ± 0.05 nM (reference) and 10.20 ± 0.04 nM (Pheroid™) (p < 0.0001). Results obtained with the in vivo antimalarial activity evaluation indicated that artemisone led to more favourable treatment outcomes than artemiside. The Peters' 4-day suppressive test was used as a basis model. With artemisone treatment recrudescence occured at 16 days post infection at a dose of 20.0 mg/kg bodyweight and at 12 days post infection at 2.5 mg/kg bodyweight. With artemiside recrudescence occurred at 8 days post infection with both the 10.0 mg/kg and 2.5 mg/kg bodyweight treatment regimens. When comparing the antimalarial effect of the drugs with and without Pheroid™ technology there was no significant difference in terms of parasite reduction or in the achieved treatment outcomes of either compounds. The pharmacokinetic parameters were evaluated in a mouse model where C57 BL6 mice were used. The compounds were administered at a dose of 50.0 mg/kg bodyweight via an oral gavage tube at a volume of 200 µl. Blood samples were collected by means of tail bleeding. Sensitive and selective LC/MS/MS methods were developed to analyze the drug concentrations in the plasma samples. The relative bioavailability of artemisone was RA = 1.0 (reference) and RA = 4.57 (Pheroid™) (p < 0.001). The absolute bioavailability was calculated as F = 0.10 (reference) and F = 0.48(Pheroid™) (p < 0.001). The boiavailability of artemiside was not dramatically enhanced by the Pheroid™ delivery system. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

The Plasmodium falciparum parasite, carried by Anopheles mosquitoes, is currently a global problem due to the rising incidence of resistance of the parasite to available antimalaria drugs. Resistance and difficult treatment groups, including pregnant woman and young children, are pressing for the development of new, safe and effective prophylactic and treatment antimalarials. Because of the extensive process of developing new drugs, researchers and health care professionals have turned to combination therapy where a fast acting antimalarial is combined with slower acting drugs, such as antibiotics. The macrolide antibiotics, erytbromycin and azithromycin, have been studied to a limited extent for their potential antimalarial effect. Certain advantages, such as their safety profile (especially that of azithromycin) in pregnancy and administration to young children, motivates continual research into the advancement of the effect these drugs exude on malaria. Drug delivery systems contribute to the efficacy of medicines, conquering several difficulties of treatment with oral medication. Pheroid™ technology is a patented drug delivery system, mainly consisting of plant and essential fatty acids, and has been demonstrated to entrap, carry and deliver pharmacologically active compounds and other useful molecules. This study compared the in vitro effects of the macrolide antibiotics on the growth of a chloroquine-resistant strain (RSA 11) of Plasmodium falciparum to the effects of the macrolides entrapped in Pheroid™ vesicles on the same strain over and extended observation period of 144 hours. ELISA assays were conducted by analysing the HRP II (histidine-rich protein) levels on a pre-coated microtitre plate. The effects of the type of formulation, concentration and time were compared. The in vitro difference between erythromycin alone and entrapped in Pheroid™ vesicles were found to be statistically significant (p = 0.000000) while the effects of both formulations did not seem to be concentration dependant (p = 0.628424). Prolonged exposure was also statistically meaningful (p = 0.008268), though it seems that exposure need not exceed 96 hours. The type of formulation, in the case of azithromycin (azithromycin alone vs. azitbromycin entrapped in Pheroid™ vesicles), proved statistically significant (P = 0.002572), while neither formulation seemed concentration dependant (P = 0.427731). Prolonged exposure was found to be statistically insignificant for azithromycin (P = 0.221941). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Stability plays an important role in the development of a new drug product. High Performance Liquid Chromatography (HPLC) is considered a stability indicating method of analysis. It is widely used in the pharmaceutical industry for the quantification of small organic molecules during stability testing. Previous stability studies conducted on Pheroid™-based drug products, experienced problems with the generation of reliable data by means of HPLC analysis. With these studies it was concluded that the inconclusive results could either be attributed to the stability of the delivery system itself and the compatibility of the active pharmaceutical ingredients (API's) with the delivery system, or to the usage of unsuitable HPLC methods. The aims of this study were to: i. determine if the Pheroid™ delivery system changes significantly over time at accelerated storage conditions and how these changes influence the HPLC analysis, ii. determine the effect of the anti-oxidant tert-butylhydroquinone (TBHQ) on the stability and HPLC analysis of the Pheroid™ delivery system, and iii. to suggest a suitable approach for the analysis of Pheroid™-based drug products. Pheroid™ microsponges, containing no API's, were prepared and stored for a period of three months at 5°C, 25°C+60%RH, 30°C+65%RH and 40°C+75%RH. Two of the four Pheroid™ formulations contained an extra anti-oxidant, namely TBHQ. Monthly HPLC analyses were done using existing methods for mefloquine and artesunate. In addition to HPLC analysis, particle size analysis and Confocal Laser Scanning Microscopy (CLSM) were undertaken to support the HPLC results and provide information concerning the overall stability of the Pheroid™ delivery system. After the completion of the above analyses, experiments were carried out to determine whether adjustments to some of the key chromatographic parameters could improve the separation of Pheroid™-based samples. The parameters that were subjected to change included the organic solvent, isocratic versus gradient separation, pH and detection wavelength. Two pro-Pheroid vesicles formulations were prepared and stored for a three month period at 40°C+75%RH only. No API was added to the one formulation while the other contained 2 mg/ml of mefloquine hydrochloride. Results obtained indicated that the Pheroid™ formulations changed after exposure to elevated temperature and humidity. The number of detectable peaks increased, longer run times became necessary and solubility in the sample solvent (methanol) decreased. Solubility of the Pheroid™ formulations in methanol was preserved to some extent by the presence of TBHQ. Physical signs of instability like discolouration and creaming were noted for TBHQ-containing formulations. TBHQ also seemed to have influenced the particle sizes, particle size distributions and structure of the Pheroid™ microsponges. With adjustments made to the HPLC method it was found that: i. the sample solvent is incompatible with the HPLC system, ii. very hydrophobic compounds are present in the Pheroid™-based samples, iii. acetontrile and methanol are unsuitable for both gradient and isocratic separation of Pheroid™-based samples, iv. more Pheroid™ components absorb at shorter wavelengths, and v. small changes in the pH values usually implemented do not influence the retention and selectivity of the Pheroid™ components. The Pheroid™ delivery system proved to be too complex and reversed hydrophobic for phase HPLC analysis. Preparation of the sample by only diluting the Pheroid™ formulations with pure methanol was not optimal. These samples introduced compounds to the column of which some caused interferences with the analyte peak while others were difficult to elute from the column. To continue using HPLC for the analysis of Pheroid™-based drug products, it is therefore recommended that attention should be given to the development of a more appropriate sample preparation procedure, like solid phase extraction or liquid-liquid extraction, one that will eliminate the effects of the Pheroid™ components. Physical instabilities noticed with the addition of TBHQ, suggest that there should also be attended to the compatibility and stability of each of the components in the Pheroid™ delivery system during formulation development. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

For a drug to have a therapeutic effect, it has to reach its site of action in sufficient quantities. The Pheroid drug delivery system enhances the absorption of drugs in various pharmacological categories and is the focus of this study. A number of patents are registered in various countries to protect its application. Pheroid technology is trademarked, but may for ease of reading, be called Pheroid(s) only. The Pheroid itself is composed of an organic carbon backbone composed of unsaturated fatty acids with some side-chain interactions that result in self-emulsifying characteristics. The resulting vesicles and nano-sponges can entrap hydrophilic, hydrophobic or amphiphilic compounds for biomedical and agricultural application and can be manipulated as to loading ability, mechanical resistance, permeability, size and solubility. Pheroid was investigated for its potential use in the areas of vaccines, peptide drugs, topical products and cosmeceuticals, antimicrobial treatments and agriculture. In all of these areas, the Pheroid has indeed shown applicability: the results showed improved uptake and/or efficacy of the entrapped chemical or biological compounds after administration by a number of administration routes. For oral administration, a precursor format, the pro-Pheroid, was used, wherein the vesicles and/or sponges are formed post-administration. Proof of concept studies on the in vivo absorption and bioavailability, as well as studies on in vitro efficacy of Pheroid-based formulations were carried out for antimicrobials, such as tuberculosis drugs, antimalarials and antiretrovirals. In all cases, the in vitro efficacy of the active compounds was increased, compared to well-known standard drug treatments. In a phase I bio-equivalence study, a Pheroid-containing combination formulation was compared against the comparative market leader. The results demonstrated that the bioavailability of the active compounds in the Pheroid was at least as good but mostly significantly better than that of the comparative medication. In addition, the incidence of side-effects was decreased in the case of the Pheroid formulations. Furthermore, in vitro results indicate that drug resistance can at least partially be negated. Pheroid technology may also be capable of protecting labile drugs such as peptides against degradation and increasing efficacy so that lower dosages can be administered less frequently and with fewer side effects. Based on in vitro and in vivo results, a number of products are currently in development. The application of Pheroid technology is potentially limitless and includes such areas as TB, malaria, cancer, AIDS, gene delivery, vaccines, patented medicines and generics and agriculture. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

For a drug to have a therapeutic effect, it has to reach its site of action in sufficient quantities. The Pheroid drug delivery system enhances the absorption of drugs in various pharmacological categories and is the focus of this study. A number of patents are registered in various countries to protect its application. Pheroid technology is trademarked, but may for ease of reading, be called Pheroid(s) only. The Pheroid itself is composed of an organic carbon backbone composed of unsaturated fatty acids with some side-chain interactions that result in self-emulsifying characteristics. The resulting vesicles and nano-sponges can entrap hydrophilic, hydrophobic or amphiphilic compounds for biomedical and agricultural application and can be manipulated as to loading ability, mechanical resistance, permeability, size and solubility. Pheroid was investigated for its potential use in the areas of vaccines, peptide drugs, topical products and cosmeceuticals, antimicrobial treatments and agriculture. In all of these areas, the Pheroid has indeed shown applicability: the results showed improved uptake and/or efficacy of the entrapped chemical or biological compounds after administration by a number of administration routes. For oral administration, a precursor format, the pro-Pheroid, was used, wherein the vesicles and/or sponges are formed post-administration. Proof of concept studies on the in vivo absorption and bioavailability, as well as studies on in vitro efficacy of Pheroid-based formulations were carried out for antimicrobials, such as tuberculosis drugs, antimalarials and antiretrovirals. In all cases, the in vitro efficacy of the active compounds was increased, compared to well-known standard drug treatments. In a phase I bio-equivalence study, a Pheroid-containing combination formulation was compared against the comparative market leader. The results demonstrated that the bioavailability of the active compounds in the Pheroid was at least as good but mostly significantly better than that of the comparative medication. In addition, the incidence of side-effects was decreased in the case of the Pheroid formulations. Furthermore, in vitro results indicate that drug resistance can at least partially be negated. Pheroid technology may also be capable of protecting labile drugs such as peptides against degradation and increasing efficacy so that lower dosages can be administered less frequently and with fewer side effects. Based on in vitro and in vivo results, a number of products are currently in development. The application of Pheroid technology is potentially limitless and includes such areas as TB, malaria, cancer, AIDS, gene delivery, vaccines, patented medicines and generics and agriculture. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.