Pheroid is a patented system comprising of a unique submicron emulsion type formulation. Pheroid vesicles consist mainly of plant and essential fatty acids and can entrap, transport and deliver pharmacologically active compounds and other useful molecules. The aim of this study was to show that a modulation of components and parameters is necessary to obtain the optimum formula to be used in pharmaceutical preparations. Non-optimal or non-predictable stability properties of emulsions can be limiting for the applications of emulsions (Bjerregaard et al., 2001:23). Careful consideration was given to the apparatus used during the processing along with the ratios of the various components added to the formulation and the storage conditions of the Pheroid vesicles. A preliminary study was performed to optimize the most accurate processing parameters during emulsification. The effect of emulsification rate and time, the temperature of the aqueous phase, the number of days the water phase were gassed, the concentration of the surfactant, cremophor® RH 40, used and the concentration of Vitamin F Ethyl Ester CLR added to the oil phase of the o/w emulsion has been studied. Quantification of the mean particle size, zeta potential, turbidity, pH and current values were used to characterize the emulsions. The samples were characterised after 1, 2, 3, 7, 14, 21 and 28 days of storage. The emulsions were also characterised with confocal laser scanning microscopy (CLSM) to measure the number and size and size distribution of the vesicles. After determination of the processing variables influencing the emulsion stability an accelerated stability test was conducted on a final formula. In the present study, accelerated stability testing employing elevated temperatures and relative humidity were used with good accuracy to predict long-term stability of an o/w emulsion kept at both 5 and 25 OC with 60 % relative humidity and 40 OC with 75 % relative humidity. The results of the stability tests were presented in histograms of the physical properties 24 hours, 1 month, 2 months and 3 months after preparation of the emulsion. It was concluded that Pheroid vesicles demonstrate much potential as a drug delivery system. The high stability of this formula allows its use in a wide variety of applications in the pharmaceutical industry. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Pheroid is a patented system comprising of a unique submicron emulsion type formulation. Pheroid vesicles consist mainly of plant and essential fatty acids and can entrap, transport and deliver pharmacologically active compounds and other useful molecules. The aim of this study was to show that a modulation of components and parameters is necessary to obtain the optimum formula to be used in pharmaceutical preparations. Non-optimal or non-predictable stability properties of emulsions can be limiting for the applications of emulsions (Bjerregaard et al., 2001:23). Careful consideration was given to the apparatus used during the processing along with the ratios of the various components added to the formulation and the storage conditions of the Pheroid vesicles. A preliminary study was performed to optimize the most accurate processing parameters during emulsification. The effect of emulsification rate and time, the temperature of the aqueous phase, the number of days the water phase were gassed, the concentration of the surfactant, cremophor® RH 40, used and the concentration of Vitamin F Ethyl Ester CLR added to the oil phase of the o/w emulsion has been studied. Quantification of the mean particle size, zeta potential, turbidity, pH and current values were used to characterize the emulsions. The samples were characterised after 1, 2, 3, 7, 14, 21 and 28 days of storage. The emulsions were also characterised with confocal laser scanning microscopy (CLSM) to measure the number and size and size distribution of the vesicles. After determination of the processing variables influencing the emulsion stability an accelerated stability test was conducted on a final formula. In the present study, accelerated stability testing employing elevated temperatures and relative humidity were used with good accuracy to predict long-term stability of an o/w emulsion kept at both 5 and 25 OC with 60 % relative humidity and 40 OC with 75 % relative humidity. The results of the stability tests were presented in histograms of the physical properties 24 hours, 1 month, 2 months and 3 months after preparation of the emulsion. It was concluded that Pheroid vesicles demonstrate much potential as a drug delivery system. The high stability of this formula allows its use in a wide variety of applications in the pharmaceutical industry. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

The unique symmetry requirements of second harmonic generation (SHG) provide exquisite selectivity to chiral crystals, enabling independent quantitative modeling of the nucleation and crystal growth of active pharmaceutical ingredients (APIs) within amorphous solid dispersions (ASDs) during accelerated in situ stability testing, and in vitro dissolution testing. ASDs, in which an API is maintained in an amorphous state within a polymer matrix, are finding increasing use to address solubility limitations of small-molecule APIs. SHG microscopy yielded limits of detection for ritonavir crystals as low as 10 ppm, which is about two orders of magnitude lower than other methods currently available for crystallinity detection in ASDs. The quantitative capabilities of SHG analysis were substantially improved further while simultaneously dramatically reducing the total sample volume and storage burden through in situ analysis. Single particle tracking of crystal growth performed in situ enabled substantial improvements in the signal to noise ratio (SNR) for recovered crystal nucleation and growth rates by nonlinear optical microscopy. Upon dissolution, the presence of solubilizing additives in biorelevant media greatly affected the generation and stabilization of supersaturated solutions. SHG microscopy was found to enable the detection of crystals even in the highly turbid Ensure Plus® system. Analysis of the SHG micrographs clearly indicated that differences in the nucleation kinetics rather than growth rates dominated the overall trends in crystallinity. For weakly basic drugs, the fate of dissolution in fasted-state simulated intestinal fluid (FaSSIF, pH 6.5) varied with the ASDs drug loading, and was highly affected by the pre-exposure to the fasted-state simulated gastric fluid (FaSSGF, pH 1.6) medium, versus the dissolution in FaSSIF medium alone. The presence of crystals during the first stage of posaconazole ASDs dissolution in FaSSGF acted as nuclei for further crystallization in the later dissolution stage in FaSSIF. The results provide insights of better formulation prediction of poorly soluble drugs, as well as understanding origins of intraluminal absorption variability for such systems

The progression of skin ageing in individuals is multifaceted and provoked by various aspects, including hereditary and a variety of environmental causes, for instance UV (ultra violet) radiation, resulting in the morphological modifications in the dermal layer of the skin (Makrantonaki & Zouboulis, 2007:40) Transformations caused by ageing skin, in which degenerative alterations exceed regenerative alterations are recognised by the thinning and wrinkling of the epidermis in conjunction with the appearance of lines, creases, crevices and furrows, particularly emphasised in lines of facial expressions (Aburjai & Natsheh, 2003:990). For human beings to continue to exist in a terrestrial atmosphere, the loss of water from the skin must be cautiously synchronised by the epidermis, a task dependent on the multifaceted character of the stratum corneum (Rawlings & Harding, 2004:43). The stratum corneum (SC) is responsible for the main resistance to the penetration of most compounds; nevertheless the skin represents as an appropriate target for delivery. The target site for anti-ageing treatment includes the epidermal and dermal layers of the skin. Therefore, the need to apply fatty materials to the skin is practically intuitive and may perhaps be as old as man’s existence itself (Lodén, 2005:672). Natural therapies have been used for several decades for taking care of skin illnesses and a wide variety of dermatological disorders, such as inflammation, phototoxicity, atopic dermatitis and alopecia areata (Aburjai & Natsheh, 2003:988). Using the skin as an alternative route for the administration of honeybush extracts for the treatment of ageing skin may be beneficial. Tea contains more than 500 chemical compounds, including, tannins, flavonoids, amino acids, vitamins, caffeine and polysaccharides. Tea polyphenols (flavonoids) have proven anti-inflammatory, antioxidant, antiallergic, antibacterial and antiviral effects (Aburjai & Natsheh, 2003:990). 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. The aim of this study was to formulate two 2% semisolid formulations containing two different honeybush extracts as the active ingredient, and to determine which of the formulations deliver mangiferin and hesperidin best to the target site (dermis). Cosmetic formulations of a natural origin, is designed to protect the skin against exogenous or endogenous harmful agents, as well as to balance the dermal homeostatis lipids altered by dermatosis and ageing (Aburjai & Natsheh, 2003:988). Stability tests over a three month period were also performed on the different formulations. To determine the stability of the different semi-solid formulations, the formulated products were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. HPLC analysis was used to determine the concentrations of the ingredients in all the formulated products. Other stability tests included appearance, pH, viscosity, mass loss, zeta potential and particle size determination. Unfortunately a change in colour, viscosity, zeta potential, mass loss, particle size and concentration of the ingredients in both the formulations, indicated that the products were unstable from the first month of stability testing. A 2% Cyclopia maculata cream as well as a 2% Cyclopia genistoides cream was formulated. Franz cell diffusion studies as well as membrane release studies were performed over a 12 h period, followed by tape stripping experiments to determine which semi-solid formulation delivered mangiferin and hesperidin the best to the dermal layer of the skin. The results of the different formulations were compared. Unfortunately there was no significant penetration by any of the honeybush extracts. Results were inconclusive and unquantifiable due to unconvincing penetration results. The antioxidant properties of both the extracts and the active ingredients were calculated. Antioxidant studies by the use of the TBA-assay method were done to determine whether the honeybush extracts, mangiferin and hesperidin as well as their semisolid formulations had any antioxidant activities. Both the honeybush extracts and the semisolid formulations showed promising results. Mangiferin and hesperidin did not show any antioxidant activity on their own, therefore the assumption can be confirmed that plants do function synergistically. A clinical study was also conducted to see whether honeybush extracts have the potential to hydrate the skin, counteracting the symptoms and signs of skin ageing. Clinical efficacy studies were done to determine whether the honeybush formulations had any skin hydrating effects in the treatment against skin ageing. The results were statistically inconclusive and variations between the subjects were very high due to skin variations at different skin sites. There was however a trend that Cyclopia genistoides performed the best. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Natural oils are regularly used in cosmetics and as treatment for numeral skin conditions (Nielsen, 2006:575). The natural products industry is a multibillion dollar industry and has grown tremendously over the past few years. Natural oils used in cosmetics contain a range of fatty acids which contribute to several valuable properties in cosmetic- and personal care products. Fatty acids are divided into saturated acids and unsaturated acids (Vermaak et al., 2011:920,922). Because of the popularity and wide diversity of skin care products, it is necessary to create products that will distinguish themselves from the rest of the commercial products. To include natural oils in skin care products is a new way to prevent skin ageing, as well as other dermatological conditions. In this study, a natural oil, namely crocodile oil was used. Crocodile oil is obtained from the fat of the Nile crocodile (Crocodylus niloticus). Crocodile oil has the same composition as human skin oil. It only differs with regard to the percentages of the ingredients present. Crocodile oil contains saturated and unsaturated fatty acids. Because of the similar composition as human skin oil, crocodile oil will rarely be allergenic when applied to human skin and therefore will be a very accepted and harmless product to use (Croc city, 2012). There are many claims of positive results when crocodile oil containing products have been used. It includes fading of freckles, treatment of acne and pimple marks, dark lines, wrinkles and laugh lines. It also includes vanishing of dark shadows, sun spots and other discolorations. It helps prevent discolorations from forming and makes the skin softer, brighter and more attractive. It also controls rashness and dryness (Croc city, 2012). Because of crocodile oil’s anti-ageing, anti-fungal and anti-bacterial effects claimed by crocodile oil suppliers, and due to the fact that little scientific data is available on crocodile oil, it was decided to investigate the claims. In this study, the aims and objectives were to use natural oil, namely crocodile oil, and investigate the fatty acid profile, anti-microbial and anti-fungal activity, anti-oxidant activity, toxicity studies, stability determination of crocodile oil lotion and clinical efficacy testing of the anti-ageing effects. To determine the fatty acid profile of crocodile oil, fatty acid methyl ester (FAME) analysis with gas chromatography were used. Identification of FAME peaks in the samples was made by comparing the relative retention times of FAME peaks from samples to those of reference standards. The composition of fatty acids in crocodile oil compared well to fatty acids found in human skin oil. Anti-microbial and anti-fungal tests were done by Envirocare Laboratories, North-West University, Potchefstroom. Staphylococcus aureus, Esterichia coli, Pseudomanas aeruginosa, Candida albicans, Brasiliensis, Propionibacterium acnes and Trichophyton rubrum cultures were used to determine the anti-microbial and anti-fungal activity of crocodile oil. Unfortunately no activity was observed. The anti-oxidant properties of crocodile oil and crocodile oil lotion were determined by using the most commonly used method for measuring Malondialdehyde (MDA) in biological samples, namely the thiobarbituric acid (TBA) test. This method is based on spectrophotometric quantification of the pink complex formed after reaction of MDA with two molecules of TBA. No anti-oxidant activity was observed in the oil or the lotion. Toxicity studies were performed by Dr. D. Goosen (BVSc Hons. Pret.) from Tswane University of Technology (Pretoria, South Africa). The studies showed that the lotion had no toxicity in the skin sensitisation, acute dermal toxicity and acute dermal irritation studies. To determine the stability of the crocodile oil lotion, the formulated products were store at 25 °C / 60% RH (relative humidity), 30 °C / 60% RH and 40 °C / 75% RH for 6 months in the original packaging as well as a glass container. The stability tests included pH, viscosity, visual appearance assessment, zeta-potential, droplet size and mass loss. The crocodile cream lotion was stable over the 6 months period in both containers. Clinical efficacy testing was performed at the CEL (Clinical Efficacy Laboratory) of the North-West University, Potchefstroom, South Africa. A short-term study over a period of 3 h was performed to investigate the hydrating effects of crocodile oil lotion. A long-term study over a period of 12 weeks was performed to examine the anti-ageing effects of crocodile oil lotion. An erythema study was also conducted to test the anti-erythema properties of crocodile oil lotion. Although the crocodile oil lotion as well as the placebo lotion showed an increase in skin hydration, there was no significant difference between the two treatments. Crocodile oil lotion also showed no anti-erythema properties. / Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

The progression of skin ageing in individuals is multifaceted and provoked by various aspects, including hereditary and a variety of environmental causes, for instance UV (ultra violet) radiation, resulting in the morphological modifications in the dermal layer of the skin (Makrantonaki & Zouboulis, 2007:40) Transformations caused by ageing skin, in which degenerative alterations exceed regenerative alterations are recognised by the thinning and wrinkling of the epidermis in conjunction with the appearance of lines, creases, crevices and furrows, particularly emphasised in lines of facial expressions (Aburjai & Natsheh, 2003:990). For human beings to continue to exist in a terrestrial atmosphere, the loss of water from the skin must be cautiously synchronised by the epidermis, a task dependent on the multifaceted character of the stratum corneum (Rawlings & Harding, 2004:43). The stratum corneum (SC) is responsible for the main resistance to the penetration of most compounds; nevertheless the skin represents as an appropriate target for delivery. The target site for anti-ageing treatment includes the epidermal and dermal layers of the skin. Therefore, the need to apply fatty materials to the skin is practically intuitive and may perhaps be as old as man’s existence itself (Lodén, 2005:672). Natural therapies have been used for several decades for taking care of skin illnesses and a wide variety of dermatological disorders, such as inflammation, phototoxicity, atopic dermatitis and alopecia areata (Aburjai & Natsheh, 2003:988). Using the skin as an alternative route for the administration of honeybush extracts for the treatment of ageing skin may be beneficial. Tea contains more than 500 chemical compounds, including, tannins, flavonoids, amino acids, vitamins, caffeine and polysaccharides. Tea polyphenols (flavonoids) have proven anti-inflammatory, antioxidant, antiallergic, antibacterial and antiviral effects (Aburjai & Natsheh, 2003:990). 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. The aim of this study was to formulate two 2% semisolid formulations containing two different honeybush extracts as the active ingredient, and to determine which of the formulations deliver mangiferin and hesperidin best to the target site (dermis). Cosmetic formulations of a natural origin, is designed to protect the skin against exogenous or endogenous harmful agents, as well as to balance the dermal homeostatis lipids altered by dermatosis and ageing (Aburjai & Natsheh, 2003:988). Stability tests over a three month period were also performed on the different formulations. To determine the stability of the different semi-solid formulations, the formulated products were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. HPLC analysis was used to determine the concentrations of the ingredients in all the formulated products. Other stability tests included appearance, pH, viscosity, mass loss, zeta potential and particle size determination. Unfortunately a change in colour, viscosity, zeta potential, mass loss, particle size and concentration of the ingredients in both the formulations, indicated that the products were unstable from the first month of stability testing. A 2% Cyclopia maculata cream as well as a 2% Cyclopia genistoides cream was formulated. Franz cell diffusion studies as well as membrane release studies were performed over a 12 h period, followed by tape stripping experiments to determine which semi-solid formulation delivered mangiferin and hesperidin the best to the dermal layer of the skin. The results of the different formulations were compared. Unfortunately there was no significant penetration by any of the honeybush extracts. Results were inconclusive and unquantifiable due to unconvincing penetration results. The antioxidant properties of both the extracts and the active ingredients were calculated. Antioxidant studies by the use of the TBA-assay method were done to determine whether the honeybush extracts, mangiferin and hesperidin as well as their semisolid formulations had any antioxidant activities. Both the honeybush extracts and the semisolid formulations showed promising results. Mangiferin and hesperidin did not show any antioxidant activity on their own, therefore the assumption can be confirmed that plants do function synergistically. A clinical study was also conducted to see whether honeybush extracts have the potential to hydrate the skin, counteracting the symptoms and signs of skin ageing. Clinical efficacy studies were done to determine whether the honeybush formulations had any skin hydrating effects in the treatment against skin ageing. The results were statistically inconclusive and variations between the subjects were very high due to skin variations at different skin sites. There was however a trend that Cyclopia genistoides performed the best. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Natural oils are regularly used in cosmetics and as treatment for numeral skin conditions (Nielsen, 2006:575). The natural products industry is a multibillion dollar industry and has grown tremendously over the past few years. Natural oils used in cosmetics contain a range of fatty acids which contribute to several valuable properties in cosmetic- and personal care products. Fatty acids are divided into saturated acids and unsaturated acids (Vermaak et al., 2011:920,922). Because of the popularity and wide diversity of skin care products, it is necessary to create products that will distinguish themselves from the rest of the commercial products. To include natural oils in skin care products is a new way to prevent skin ageing, as well as other dermatological conditions. In this study, a natural oil, namely crocodile oil was used. Crocodile oil is obtained from the fat of the Nile crocodile (Crocodylus niloticus). Crocodile oil has the same composition as human skin oil. It only differs with regard to the percentages of the ingredients present. Crocodile oil contains saturated and unsaturated fatty acids. Because of the similar composition as human skin oil, crocodile oil will rarely be allergenic when applied to human skin and therefore will be a very accepted and harmless product to use (Croc city, 2012). There are many claims of positive results when crocodile oil containing products have been used. It includes fading of freckles, treatment of acne and pimple marks, dark lines, wrinkles and laugh lines. It also includes vanishing of dark shadows, sun spots and other discolorations. It helps prevent discolorations from forming and makes the skin softer, brighter and more attractive. It also controls rashness and dryness (Croc city, 2012). Because of crocodile oil’s anti-ageing, anti-fungal and anti-bacterial effects claimed by crocodile oil suppliers, and due to the fact that little scientific data is available on crocodile oil, it was decided to investigate the claims. In this study, the aims and objectives were to use natural oil, namely crocodile oil, and investigate the fatty acid profile, anti-microbial and anti-fungal activity, anti-oxidant activity, toxicity studies, stability determination of crocodile oil lotion and clinical efficacy testing of the anti-ageing effects. To determine the fatty acid profile of crocodile oil, fatty acid methyl ester (FAME) analysis with gas chromatography were used. Identification of FAME peaks in the samples was made by comparing the relative retention times of FAME peaks from samples to those of reference standards. The composition of fatty acids in crocodile oil compared well to fatty acids found in human skin oil. Anti-microbial and anti-fungal tests were done by Envirocare Laboratories, North-West University, Potchefstroom. Staphylococcus aureus, Esterichia coli, Pseudomanas aeruginosa, Candida albicans, Brasiliensis, Propionibacterium acnes and Trichophyton rubrum cultures were used to determine the anti-microbial and anti-fungal activity of crocodile oil. Unfortunately no activity was observed. The anti-oxidant properties of crocodile oil and crocodile oil lotion were determined by using the most commonly used method for measuring Malondialdehyde (MDA) in biological samples, namely the thiobarbituric acid (TBA) test. This method is based on spectrophotometric quantification of the pink complex formed after reaction of MDA with two molecules of TBA. No anti-oxidant activity was observed in the oil or the lotion. Toxicity studies were performed by Dr. D. Goosen (BVSc Hons. Pret.) from Tswane University of Technology (Pretoria, South Africa). The studies showed that the lotion had no toxicity in the skin sensitisation, acute dermal toxicity and acute dermal irritation studies. To determine the stability of the crocodile oil lotion, the formulated products were store at 25 °C / 60% RH (relative humidity), 30 °C / 60% RH and 40 °C / 75% RH for 6 months in the original packaging as well as a glass container. The stability tests included pH, viscosity, visual appearance assessment, zeta-potential, droplet size and mass loss. The crocodile cream lotion was stable over the 6 months period in both containers. Clinical efficacy testing was performed at the CEL (Clinical Efficacy Laboratory) of the North-West University, Potchefstroom, South Africa. A short-term study over a period of 3 h was performed to investigate the hydrating effects of crocodile oil lotion. A long-term study over a period of 12 weeks was performed to examine the anti-ageing effects of crocodile oil lotion. An erythema study was also conducted to test the anti-erythema properties of crocodile oil lotion. Although the crocodile oil lotion as well as the placebo lotion showed an increase in skin hydration, there was no significant difference between the two treatments. Crocodile oil lotion also showed no anti-erythema properties. / Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Made available in DSpace on 2015-08-19T13:52:54Z (GMT). No. of bitstreams: 2 11.pdf: 3707565 bytes, checksum: 12296eaba653f97c49408b84cc04f255 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos/Farmanguinhos. Rio de Janeiro, RJ, Brasil. / As formas farmacêuticas sólidas de uso oral, sobretudo os comprimidos, são as mais utilizadas na terapêutica, pois são de fácil administração e apresentam alta produtividade e um custo relativamente baixo, além de proporcionarem ao fármaco um meio mais estável em relação às formas semi-sólidas e líquidas. No entanto, um medicamento na forma sólida pode sofrer alterações devido à ação de vários fatores como umidade, temperatura, luz e oxigênio do ambiente e pelas características do próprio estado sólido da substância ativa e dos excipientes empregados na formulação. A instabilidade de um fármaco, na forma isolada ou em uma formulação, pode alterar vários parâmetros de qualidade como aspecto, teor, dissolução e perfil de dissolução. O perfil de dissolução de um medicamento é um parâmetro de qualidade que deve ser avaliado durante a produção e estabilidade das formas farmacêuticas sólidas orais, pois a alteração do mesmo durante o período de armazenamento pode alterar a quantidade de fármaco disponível para absorção, podendo comprometer a sua biodisponibilidade e eficácia terapêutica. Nesse estudo o perfil de dissolução de comprimidos de prednisona 20mg bioequivalentes do medicamento referencia e de três formulações teste foram avaliadas, ao longo do estudo de estabilidade. Durante o estudo os comprimidos de prednisona e o insumo farmacêutico ativo(IFA) prednisona de dois diferentes fabricantes foram caracterizado quanto às suas propriedades físicas e físico-químicas. O IFA também foi avaliado quanto a sua permeabilidade em células Caco-2. Os dados obtidos foram utilizados para elaborar um estudo de correlação in vitro-in silico-in vivo e desenvolver estudos de predição de biodisponibilidade in silico. Os resultadospermitiram verificar que os perfis de dissolução entre os comprimidos do medicamento referência e dos lotes teste não se mantiveram equivalentes ao longo do estudo. Verificou-se também que ambas as amostras do IFA prednisona tratavam-se na mesma forma cristalina e que essa não sofreu transição durante o estudo, que uma correlação CIVIV não pode ser obtida e que A simulação da biodisponibilidade realizada para a prednisona utilizando o software GastroPlus TM foi bem sucedida comparada os resultados obtidos in vivo. / The solid dosage forms for oral use, especially tablets are the most used in therapy because they are easily adminis tered and have high productivity relatively low cost and to provide a more stable drug to the forms semi-solid net. However, a drug in solid form may change due to the action of various factors such as humidity, temperature, light and oxygen from the envir onment and the characteristics of the solid state of the active substance and the excipients used in the formulation. The instability of a drug, in alone or in a formulation can change various quality parameters such as aspect, content, dissolution and dis solution profile. The dissolution profile of a drug is a quality parameter that must be evaluated during the production and stability of solid oral dosage forms, for the same change during the storage period can change the amount of drug available for absorption, which may compromise the the bioavailability and therapeutic efficacy. In this study the dissolution profile of 20 mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated throughout the stability testing. During the study,prednisone tablets and the active pharmaceutical ingredient (API) prednisone,two different manufacturers were characterized with respect to their physical properties and physicochemical. The API was also evaluated for their permeability in Caco-2 cells. The data were used to develop a correlation study in vitro-in silico-vivo studies and develop in silico prediction of bioavailability. The results showed that the dissolution profiles of the drug from the tablets and the reference test batches did not remain equal throughout the study. It was also noted that both samples API prednisone treated in the same crystal form and that the transition has not suffered during the study, a correlation IVIVC can’t be obtained and bioavailability of simulation performed for prednisone using software GastroPlus TM was successful compared the results obtained in vivo.

O interesse mundial por produtos derivados de plantas medicinais cresceu vertiginosamente nos últimos anos. Produtos derivados de plantas medicinais são misturas multicomponentes e sua eficácia pode estar associada a mais de um composto tornando o seu controle da qualidade tarefa árdua. Apesar de grandes investimentos em pesquisa terem sido feitos para a comprovação da eficácia e segurança dos medicamentos derivados de plantas medicinais, poucos são os trabalhos científicos que dizem respeito à manutenção da qualidade desses produtos. Extratos secos de plantas medicinais possuem efeito farmacológico devido à presença de substâncias ativas que estão sujeitas a reações de degradação. A velocidade dessas reações pode ser prevista através do estudo de estabilidade que envolve o armazenamento dos extratos em diversas condições (diferentes temperatura e umidade relativa do ar). Por esse motivo, o objetivo dessa tese foi o estudo da influência do processo de obtenção, das condições de armazenamento e das propriedades físico-químicas sobre a estabilidade de extratos secos padronizados de plantas medicinais. Visando o entendimento dos fatores que afetam a estabilidade de produtos naturais, os extratos foram caracterizados em relação à composição (presença de açúcares redutores, proteínas, lipídeos, carboidratos de alta e baixa massa molecular, acidez titulável), análise térmica, determinação de isotermas de adsorção (ou absorção), espectroscopia de Infravermelho e difração de raios-X. Após caracterização, os extratos secos foram armazenados em câmara climática visando avaliar a variação das propriedades físicas e químicas em função do período e condições de armazenamento. Para um entendimento mais amplo dos fatores que proporcionam maiores influências na estabilidade de produtos derivados de plantas medicinais, extratos secos foram obtidos a partir de três plantas medicinais amplamente utilizadas na medicina popular brasileira: Bauhinia forficata (hipoglicemiante), Maytenus ilicifolia (anti-úlcera gástrica) e Passiflora alata (sedativo e ansiolítico). Os extratos secos foram obtidos a partir de dois distintos processos de secagem o spray-drying (secagem por nebulização) e o processo leito de jorro. Os resultados obtidos indicam que todos os extratos secos analisados apresentaram algum tipo de alteração dos padrões de qualidade inicialmente observados. O que não foi possível mostrar é o quanto essas perdas poderiam influenciar na atividade biológica desses produtos. Por se tratar de uma mistura multicomponente é pouco provável que se estabeleçam técnicas que possam assegurar que todos esses componentes sejam mantidos durante todo o período de armazenamento. Porém, fenômenos importantes para a atividade farmacológica como a cristalização das substâncias, (demonstrada através dos espectros de raios-X), ou a degradação de marcadores (CLAE e espectrofotometria) puderam ser monitorados e previstos. / Nowadays, the global interest for herbal drugs has increased significantly. Herbal medicinal products are a complex mixture of substances and their efficacy might be associated with one or more compounds. For this reason, the quality control of herbal products is a challenging task. In spite of a great increase in researches concerning the pharmacological and toxicological aspects of herbal drugs, there is a lack of scientific works related to the quality maintenance of these products. Among all the herbal medicinal products the standardized dried extracts are gaining more interest as a way of controlling dosage and increasing safety of the phytopharmaceuticals. Herbal dried extracts are effective due to the presence of active substances, and these substances may degrade. The rate of degradation can be measured through stability testing what is done through the storage of the product in different storage conditions (temperature and relative humidity). For this reason, the aim of this thesis was the study of the influence of the obtainment process, storage conditions and physical and chemical properties in the standardized dried extracts stability. For the understanding of the factors which affects the stability of the natural products, the extracts were characterized in relation to their composition (reducing sugars, proteins, lipids, low and high molecular weight carbohydrates, and titrable acidity), the calorimetric profile, determination of sorption isotherms, near infrared spectroscopy and X-ray diffraction analysis. Furthermore, the dried extracts were stored in a climatic chamber for the evaluation of the physical and chemical properties variations in relation to the time and storage conditions. Herbal dried extracts obtained from three plant species commonly used in Brazil were used in this study: Bauhinia forficata (hypoglycemiant), Maytenus ilicifolia (antiulcerogenic) and Passiflora alata (sedative and anxiolytic). The dried extracts were produced trough two different drying processes the spray drying and the spouted bed drying. In conclusion, the results obtained showed that all the studied extracts presented some deviation of the initial standards owing to its great sensibility to the environmental conditions. However, it was not possible to show how this lost would affect the effectiveness of these products. Moreover, for being such a complex mixture of components it is almost impossible the establishment of techniques that will assure that all this components will remain unchanged during the storage period. Nevertheless, some important factors for the pharmacological activity of substances as the crystallization (X-ray diffraction) or the degradation of the chemical markers (high performance liquid chromatography and spectrophotometry) can be evaluate and previewed

O interesse mundial por produtos derivados de plantas medicinais cresceu vertiginosamente nos últimos anos. Produtos derivados de plantas medicinais são misturas multicomponentes e sua eficácia pode estar associada a mais de um composto tornando o seu controle da qualidade tarefa árdua. Apesar de grandes investimentos em pesquisa terem sido feitos para a comprovação da eficácia e segurança dos medicamentos derivados de plantas medicinais, poucos são os trabalhos científicos que dizem respeito à manutenção da qualidade desses produtos. Extratos secos de plantas medicinais possuem efeito farmacológico devido à presença de substâncias ativas que estão sujeitas a reações de degradação. A velocidade dessas reações pode ser prevista através do estudo de estabilidade que envolve o armazenamento dos extratos em diversas condições (diferentes temperatura e umidade relativa do ar). Por esse motivo, o objetivo dessa tese foi o estudo da influência do processo de obtenção, das condições de armazenamento e das propriedades físico-químicas sobre a estabilidade de extratos secos padronizados de plantas medicinais. Visando o entendimento dos fatores que afetam a estabilidade de produtos naturais, os extratos foram caracterizados em relação à composição (presença de açúcares redutores, proteínas, lipídeos, carboidratos de alta e baixa massa molecular, acidez titulável), análise térmica, determinação de isotermas de adsorção (ou absorção), espectroscopia de Infravermelho e difração de raios-X. Após caracterização, os extratos secos foram armazenados em câmara climática visando avaliar a variação das propriedades físicas e químicas em função do período e condições de armazenamento. Para um entendimento mais amplo dos fatores que proporcionam maiores influências na estabilidade de produtos derivados de plantas medicinais, extratos secos foram obtidos a partir de três plantas medicinais amplamente utilizadas na medicina popular brasileira: Bauhinia forficata (hipoglicemiante), Maytenus ilicifolia (anti-úlcera gástrica) e Passiflora alata (sedativo e ansiolítico). Os extratos secos foram obtidos a partir de dois distintos processos de secagem o spray-drying (secagem por nebulização) e o processo leito de jorro. Os resultados obtidos indicam que todos os extratos secos analisados apresentaram algum tipo de alteração dos padrões de qualidade inicialmente observados. O que não foi possível mostrar é o quanto essas perdas poderiam influenciar na atividade biológica desses produtos. Por se tratar de uma mistura multicomponente é pouco provável que se estabeleçam técnicas que possam assegurar que todos esses componentes sejam mantidos durante todo o período de armazenamento. Porém, fenômenos importantes para a atividade farmacológica como a cristalização das substâncias, (demonstrada através dos espectros de raios-X), ou a degradação de marcadores (CLAE e espectrofotometria) puderam ser monitorados e previstos. / Nowadays, the global interest for herbal drugs has increased significantly. Herbal medicinal products are a complex mixture of substances and their efficacy might be associated with one or more compounds. For this reason, the quality control of herbal products is a challenging task. In spite of a great increase in researches concerning the pharmacological and toxicological aspects of herbal drugs, there is a lack of scientific works related to the quality maintenance of these products. Among all the herbal medicinal products the standardized dried extracts are gaining more interest as a way of controlling dosage and increasing safety of the phytopharmaceuticals. Herbal dried extracts are effective due to the presence of active substances, and these substances may degrade. The rate of degradation can be measured through stability testing what is done through the storage of the product in different storage conditions (temperature and relative humidity). For this reason, the aim of this thesis was the study of the influence of the obtainment process, storage conditions and physical and chemical properties in the standardized dried extracts stability. For the understanding of the factors which affects the stability of the natural products, the extracts were characterized in relation to their composition (reducing sugars, proteins, lipids, low and high molecular weight carbohydrates, and titrable acidity), the calorimetric profile, determination of sorption isotherms, near infrared spectroscopy and X-ray diffraction analysis. Furthermore, the dried extracts were stored in a climatic chamber for the evaluation of the physical and chemical properties variations in relation to the time and storage conditions. Herbal dried extracts obtained from three plant species commonly used in Brazil were used in this study: Bauhinia forficata (hypoglycemiant), Maytenus ilicifolia (antiulcerogenic) and Passiflora alata (sedative and anxiolytic). The dried extracts were produced trough two different drying processes the spray drying and the spouted bed drying. In conclusion, the results obtained showed that all the studied extracts presented some deviation of the initial standards owing to its great sensibility to the environmental conditions. However, it was not possible to show how this lost would affect the effectiveness of these products. Moreover, for being such a complex mixture of components it is almost impossible the establishment of techniques that will assure that all this components will remain unchanged during the storage period. Nevertheless, some important factors for the pharmacological activity of substances as the crystallization (X-ray diffraction) or the degradation of the chemical markers (high performance liquid chromatography and spectrophotometry) can be evaluate and previewed