L’objectif de ce travail de thèse est d’étudier la relation entre la méthode de préparation des nanoparticules, les propriétés colloïdales et l’encapsulation d’un principe actif à usage pédiatrique. Dans ce but, le diclofenac a été utilisé comme molécule modèle et les nanoparticules ont été préparées via la nanoprécipitation et l’émulsification-diffusion. Des études fondamentales et systématiques ont permis de mettre en évidence l'existence de différences notables entre les propriétés électrocinétiques et l'efficacité d’encapsulation en fonction du procédé utilisé pour la préparation des particules. Ces propriétés colloïdales et physico-chimiques sont primordiales pour la bonne stabilité des dispersions de nanosphères et des nanocapsules et pour le comportement de ces vecteurs lors d’utilisation in vivo. Cette étude a permis de proposer et de discuter le mécanisme de formation des nanoparticules en se basant sur le comportement des variables critiques du procédé et de la formulation, les propriétés de surface et l'efficacité d’encapsulation de l’actif modèle / The objective of this PhD thesis is to point out the relationship between the preparation method of the nanoparticles, the colloidal properties and the encapsulation efficiency of a given active molecule for paediatric purpose. In this direction, diclofenac was used as model molecule and the nanoparticles were prepared via the nanoprecipitation and the emulsification-diffusion processes. The conducted fundamental and systematic studies rend evident notable differences between the two processes, particularly in the electrokinetic properties of the particles and the effectiveness of the drug encapsulation. These colloidal and physicochemical properties are paramount for the good stability of the nanoparticles and their in vivo use. This research work made it possible to propose and to discuss the mechanism of nanoparticle formation from the behavior of key variables of the process and the recipe used, the surface properties of the particles and the effectiveness of encapsulation of the model drug

Microneedles are a minimally invasive method for delivering drugs through the impermeable skin layers, and have been used to deliver a variety of compounds including macromolecules, vaccines, and naltrexone. Microneedles can be applied to the skin once, creating micropores that allow for drug delivery into the underlying circulation from a drug formulation. The utility of this technique, however, is blunted by rapid micropore closure. This research project sought to: 1) characterize micropore lifetime and re-sealing kinetics, and 2) prolong micropore lifetime via inhibition of the skin’s barrier restoration processes. Impedance spectroscopy was used as a surrogate technique in animals and humans to measure micropore formation and lifetime. A proof of concept study in humans, using impedance spectroscopy, demonstrated that diclofenac (a topical anti-inflammatory) applied to microporated skin resulted in slower re-sealing kinetics compared to placebo, in agreement with previous animal studies. The clinical feasibility of prolonging micropore lifetime with diclofenac was confirmed via 7-day delivery of naltrexone through microneedle treated skin in humans (compared to 72 hour delivery with placebo). Lastly, naltrexone gels with calcium salts were applied to microneedle treated skin (hairless guinea pigs) to restore the altered epidermal calcium gradient; this method did not significantly extend micropore lifetime.

A dissertation presented in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Technikon Natal, 2001. / There are many non-surgical treatments that are available to patients with low back pain but few have been proven effective in controlled clinical trials. Arguably, the treatments with the greatest evidence for efficacy are nonsteroidal anti-inflammatory drugs (NSAIDs), some muscle relaxants and spinal manipulation (Deyo et al.(1983) and Shekelle et al.(1992). Non-steroidal antiinflammatory drugs are the most widely used agents for musculoskeletal pain and inflammation. The widespread use of NSAIDs augments the impact not only of their benefits but also the risk of their adverse effects. The effectiveness of chiropractic management is now firmly established for most patients with acute and chronic low-back pain (Koes et aI.1996). The purpose of this study was to determine the relative efficacy of combined diclofenac sodium therapy and spinal manipulation compared to combined placebo therapy and spinal manipulation in the treatment of mechanical low back pain. Sixty subjects were selected and randomly divided into two groups of thirty subjects. Subjects were treated four times over a two-week period, including a diclofenac or placebo medication course, taken three times daily for five days, starting from the first consultation. The results of the Numerical Pain Rating Scale-101, Revised Oswestry Low Back Pain Disability Questionnaire, Orthopaedic Rating Scale and Algometer readings were taken before the first, third and fourth consultations. The statistical tests used were the parametric two-sample unpaired t-tests and the paired t-tests, and the nonparametric intra-group Friedman test, multiple comparison procedure, Wilcoxon Signed Ranks test and the inter-group Mann Whitney U-test at the 95% level of significance using the SPSS statistical package. There was a statistically significant improvement in both treatment groups for both subjective and objective clinical findings, suggesting that spinal manipulation combined with either an NSAID or placebo medication will ultimately give relief to a patient suffering from lower back pain. The conclusions / M

Para se garantir a eficácia, a segurança e a qualidade de um produto farmacêutico é necessário o conhecimento das propriedades físicas e físico-químicas do fármaco e dos excipientes empregados nas formulações, bem como dos procedimentos relacionados aos processos de produção. Conhecer as propriedades do estado sólido é de fundamental importância e relevância na área farmacêutica uma vez que estas propriedades têm um impacto profundo sobre a solubilidade, biodisponibilidade e estabilidade química dos fármacos. Os dados de difração de raio-X, ressonância quadrupolar nuclear, espectroscopia de infravermelho, análise térmica e microscopia foram usados para a caracterização e identificação das diferentes amostras de diclofenaco de sódio, duas comercializadas no Brasil (DPB1 e DPB3) e uma na Argentina (DPA2). Foi observada a presença das formas anidro, pentahidrato e desconhecida nas formulações comerciais DPB3, DPA2 e DPB1, respectivamente. A análise quantitativa do diclofenaco de sódio para os estudos in vitro de dissolução foi realizada por cromatografia líquida de alta eficiência empregando uma coluna de fase reversa C-18 e acetonitrila:ácido acético 0,7 mol/L (1:1, v/v) como fase móvel. No meio de dissolução composto por tampão fosfato de sódio 0,2 mol/L, pH 6,8 foi observada uma dissolução de 100% para as três formulações de diclofenaco de sódio em 1 hora. Para o meio de dissolução composto por tampão fosfato de sódio 0,2 mol/L, pH 4,5 a porcentagem do fármaco dissolvido foi de apenas 4% nas formulações avaliadas. Entretanto, diferenças na solubilidade entre as formulações avaliadas foram observadas, o que pode ser devido às diferenças na estrutura cristalina do diclofenaco de sódio. Também foram realizados estudos de dissolução apenas nas amostras anidro e hidrato, sem a interferência de revestimentos ou excipientes, nos meios de dissolução descritos acima e em solução de HCl 0,1 mol/L pH 1,2. Foi observado que a amostra anidra apresentou uma diferença estatisticamente significativa no perfil in vitro de dissolução comparada a forma hidratada em solução de pH 6,8. Para os demais valores de pH não foram observadas diferenças estatisticamente significativas nos perfis de dissolução. Também foi desenvolvido e validado um método para análise do diclofenaco de sódio em plasma, empregando a coluna RP-18 (125x4,6 mm, partículas de 5 m) protegida por uma coluna de guarda RP-18 (4,0x4,0 mm) e fase móvel composta por acetonitrila:ácido acético 0,7 mol/L (1:1, v/v). Foi realizada a extração líquido-líquido como procedimento de preparação da amostra usando uma mistura de hexano:éter (1:1, v/v) como solvente extrator. O método foi validado avaliando os parâmetros linearidade, recuperação, precisão e exatidão, limite de quantificação e estabilidade. Todos os parâmetros avaliados apresentaram resultados adequados e aceitos pela literatura. Posteriormente, o método desenvolvido e validado foi aplicado em um estudo piloto para avaliar a concentração plasmática do diclofenaco de sódio em coelhos. Também foi avaliada a influência das diferentes formas cristalinas do diclofenaco de sódio na resposta febril induzida por LPS em coelhos. Neste estudo não foi observada nenhuma diferença estatisticamente significativa na redução da resposta febril para as diferentes amostras avaliadas. / To assure effectiveness, security and quality of pharmaceutical products, the knowledge of the physical and chemical-physical properties of the drugs and the excipients used in formulations are necessary, as well as the proceeding related to the production processes. To know the properties of the solid state is important and relevant in the pharmaceutical area because they have a deep impact on the solubility, bioavailability and chemical stability of the drugs. Data of X-ray diffraction, nuclear quadrupole resonance, infrared spectroscopy, thermal analysis and scanning electron microscopy have been used for the characterization and identification of the different samples of diclofenac sodium. The presence of anhydrous, pentahydrate and unknown forms were observed in commercial formulations DPB3, DPA2 and DPB1, respectively. Quantitative analysis of the diclofenac sodium for studies in vitro of dissolution was carried out by high performance liquid chromatography using the column reverse phase C-18 and acetonitrila:acetic acid 0,7 mol/L (1:1, v/v) as mobile phase. Release profiles in vitro of dissolution of commercial diclofenac sodium formulations were evaluated using different dissolution medium. In the phosphate buffer solution 0.2 mol/L pH 6.8, it was observed dissolution of 100% for the three formulations of diclofenac sodium in 1 hour while in the phosphate buffer solution 0.2 mol/L pH 4.5, the percentage of drug dissolved was only 4%. However, differences in the solubility between the formulations evaluated were observed, which can be due to the differences in the crystalline structure of diclofenac sodium. Dissolution studies in the samples anhydrous and hydrate were carried out, without the interference of coverings or excipients, in the dissolution medium described above and in the solution 0.1 HCl mol/L pH 1.2. It was observed that the anhydrous sample showed a significant statistical difference in the in vitro dissolution profile when compared with hydrate form (pH 6.8). For the others values of pH, significant statistical differences in the dissolution profiles were not observed. It was also developed and validated a method of analysis of diclofenac sodium in plasma using the column RP-18 (125x4.6mm, particle size 5 µm) protected by a column of guard RP-18 (4.0x4.0 mm) and acetonitrila:acetic acid 0,7 mol/L (1:1, v/v) as mobile phase. Sample preparation was performed by liquidliquid extraction using hexano:ether as extracting solvent after acidification with 2.0 mol/L hydrochloric acid. The method was validated by evaluation of parameters such as linearity, recovery, precision and accuracy, limit of quantification and stability. All the evaluated parameters had presented results adequate and accepted in the literature. Subsequently, the developed and validated method was applied in a pilot study to evaluate the plasmatic concentration of the diclofenac sodium in rabbits. It was also evaluated the influence of the different crystalline forms of the diclofenac sodium in the LPS induced fever in rabbits. In this study no significant statistical difference was observed in the reduction of the febrile response within the different samples evaluated.

Os resíduos de fármacos presentes em matrizes ambientais têm sido foco em pesquisas no mundo todo. Este tema tem sido bastante discutido devido ao fato de que fármacos são freqüentemente encontrados em efluentes de estações de tratamento de esgotos (ETE´s), águas de abastecimento público e em outras matrizes ambientais, tais como solos, sedimentos e águas naturais em concentrações na faixa de µg L-1 e ng L-1. A grande preocupação da presença de resíduos de fármacos na água são os potenciais efeitos adversos para a saúde humana, animal e de organismos aquáticos. Neste trabalho estudou-se o diclofenaco sódico, por ser um dos antiinflamatórios mais prescritos pelos médicos. O método utilizado para a extração do diclofenaco sódico de amostras de efluentes domésticos da ETE de Araraquara-SP foi à extração em fase sólida, e subseqüentemente a determinação por cromatografia líquida de alta eficiência com detector UV. O método foi validado e a recuperação foi de 94-105%. Constatou-se a presença do diclofenaco sódico nas amostras do efluente doméstico da cidade de Araraquara-SP antes e após o tratamento e as concentrações foram 2,12 e 3,52 µg L-1 na coleta feita em março e 18,0 e 22,0µg L-1 na coleta feita em setembro. / The pharmacos residues that are present in the environmental matrices has been a focus of research all over the world. This subject has been discussed because the fact that pharmacos are frequently found in effluents of sewage treatment plants (STPs), public water supply and in others environmental matrices, such as the soil, sediments and water springs in concentrations between µg L-1 and ng L-1. The biggest concern of pharmacos residues in the water are the adverse effects for the human health and the other species too. So, in this research the sodium diclofenac was studied for being the most prescribed anti-inflammatory by the doctors. The method used for the extraction of the sodium diclofenac of samples from the domestic effluent at STP-Araraquara (SP) was the extraction in solid phase, and subsequently the determination by liquid chromatography of high efficiency with UV detector. The method was validated and the recovery was of 94 to 105%. The results of the research have shown the presence of sodium diclofenac in the samples of Araraquara\'s domestic effluent before and after the treatment and the concentrations were 2,12 and 3,52 µg L-1 in the collection made in March and 18,0 and 22,0µg L-1 in the collection made in September.

Bis zu 95 % der Wirkstoffe von Arzneimittel der Humanmedizin werden unverändert ausgeschieden oder gelangen über die täglichen Hygiene in den Wasserkreislauf. Die meisten Substanzen werden sehr schnell und vollständig abgebaut oder liegen in Konzentrationen vor, in denen sie keine Gefährdung für die Umwelt und den Menschen darstellen. Im Gegensatz dazu gibt es aber auch Substanzen, die nur sehr schwer abgebaut werden können (persistent sind) und für die bereits negative Langzeiteffekte in umweltrelevanten Konzentrationen für Tiere nachgewiesen wurden. Ein Beispiel dafür ist der schmerzstillende Wirkstoff Diclofenac. Aus diesem Grund und wegen der guten Kenntnislage hinsichtlich Vorkommen, Abbauprodukte und Analytik wurde Diclofenac als Referenzverbindung für die Experimente im Rahmen dieses Projekts verwendet. Aufgrund der geringen Konzentration von Diclofenac in Wasser und der chemischen Stabilität von Diclofenac sowie einiger anderer Spurenstoffe sind herkömmliche Wasserbehandlungsverfahren, wie sie derzeit in Kläranlangen verwendet werden, ineffizient oder zu teuer. Deshalb gibt es zahlreiche Bemühungen, alternative und umweltschonende Behandlungsverfahren zur Entfernung von Arzneimittelrückständen aus Wasser zu entwickeln, die einen vollständigen Abbau der Rückstände ermöglichen. Idealerweise sollten technische Lösungen zur Verfügung stehen, die gegebenenfalls in jedem Land der Erde einsetzbar wären. Der in diesem Projekt verfolgte Ansatz zur Entwicklung fotokatalytischer Schichten, die idealerweise bereits bei Tageslicht eine ausreichend hohe Aktivität aufweisen, ist besonders interessant, da es nach Optimierung weder des zusätzlichen Einsatzes von Chemikalien noch des Einsatzes von Energie bedarf. So werden durch die Bestrahlung des Katalysators (z.B. ZnO, TiO2) mit künstlichem UV-Licht, perspektifisch aber mit UV-A-Strahlung der Sonne sowohl Wasser als auch Luftsauerstoff zu reaktiven Hydroxylradikalen umgesetzt, die letztendlich die unspezifischen Spaltung organischer Verbindungen im Wasser bewirken. Voraussetzung für die Optimierung hinsichtlich katalytischer Aktivität und Empfindlichkeit gegenüber Tageslicht ist ein Herstellungsverfahren, das die Optimierung der fotokatalytischen Schichten bezüglich verschiedener Parameter (optimale Größe, enge Größenverteilung, Möglichkeit der einfachen Dotierung, Verhinderung der Agglomeration bei gleichzeitiger dauerhafter Immobilisierung) erlaubt. Diesbezüglich besonders aussichtsreich ist die Verwendung von hoch geordneten bakteriellen Hüllproteinen sogenannten „surface-layer“ (S-Layer)-Proteinen, die sowohl eine einfache Herstellung von fotokatalytisch aktiven Nanopartikeln aus verschiedenen Elementen erlauben, als auch zur Beschichtung verschiedener Materialien geeignet sind. Ein Ziel im Projekt ist die Herstellung von reinen und dotierten ZnO und TiO2-Nanopartikeln zur Eliminierung von Diclofenac aus Wasser (siehe Abbildung 1). Dabei dienen S-Layer verschiedener Bakterien und damit Proteinschichten mit unterschiedlichen Symmetrien, Gitterabständen und Porengröße als Template für die Herstellung von Nanopartikeln verschiedener aber definierter Größe. Darüber hinaus werden die S-Layer im Projekt als Trenn- und Immobilisierungsschicht für die erzeugten Nanopartikel genutzt. Letzteres vor allem zur Verhinderung einer Agglomeration und des Austrags der Nanopartikel, was beides einen Verlust der katalytischen Aktivität entsprechender Schichten bedeuten würde. Als Träger werden im Rahmen des Projekts verschiedene in technischen Anwendungen genutzte Materialien dahin gehend überprüft, in wie weit sich S-Layer darauf abscheiden lassen und stabile Schichten ausbilden und darauf aufbauend ein Trägermaterial für die Herstellung fotokatalytisch aktiver Beschichtungen ausgewählt. Gleichzeitig war es Ziel des Projektes, die Biomassegewinnung hinsichtlich eines Upscalings und hinsichtlich der Kosten zu optimieren. Ausgehend von dieser konkreten wissenschaftlichen Fragestellung war es auch Ziel des Projektes, ein verwertungsorientiertes Netzwerk aufzubauen. Dies vor allem zur Sicherung der Fortentwicklung der neuen Materialien und der Weiterführung der begonnenen Arbeiten in dem konkreten Forschungsgebiet mit dem Ziel der Entwicklung eines marktreifen Produktes aber auch zur Etablierung einer dauerhaften Kooperation zwischen den verschiedenen Forschungs- und Industriepartnern. Diese Ziele sollten insbesondere über eine Vernetzung von Instituten innerhalb der Leibniz-Gemeinschaft, weiteren regionalen und überregionalen Forschungseinrichtungen sowie Industriepartnern erreicht werden. Die sehr gute gerätetechnische Ausstattung, die im vorliegenden Fall über die Projektmittel erreicht wurde, war nicht nur Voraussetzung zur Durchführung der geplanten Forschungs- und Entwicklungsarbeiten und zur Herstellung von Materialien im kleintechnischen Maßstab, sondern erhöhte auch die Attraktivität des Teams als Projektpartner weiter und nachhaltig. Erfahrungen aus dem Projekt und dem Prozess der Netzwerkbildung sollen insbesondere unter Einbeziehung der Geschäftsstelle der Leibniz-Gemeinschaft zur Entwicklung eines Prozessleitfadens für die Bildung von Verwertungs- und Transfernetzwerken innerhalb der Leibniz-Gemeinschaft genutzt werden.

Our laboratory has previously demonstrated that experimental peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan in Sprague Dawley rats, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). Increased P-gp functional expression was associated with a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. The present study examined whether the PIP-induced increase in P-gp functional expression was due to changes in intracellular trafficking (i.e., localization of P-gp), mediated by changes in the association of P-gp and caveolin-1, a key trafficking protein. These studies also determined if the drug diclofenac, a non-steroidal antiinflammatory (NSAID) that is commonly administered in conjunction with opioids during peripheral inflammatory pain (PIP), altered or modulated P-gp functional expression providing evidence of a drug-drug interaction. Confocal microscopy and subcellular fractionation revealed that under conditions of PIP, the disassembly of high-molecular weight P-gp-containing structures result in an increase in P-gp ATPase activity and changes in the localization of P-gp. Western blot analysis demonstrated further an increase in P-gp expression in rat brain microvessels following PIP induction and also after diclofenac treatment alone in the absence of PIP. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased radiolabeled- morphine uptake into the brain. This concurrent administration of NSAIDs and opioids in the presence of a pathophysiological stressor (i.e., pain/inflammation) may result in clinically significant drug-drug interactions that may impair the desired pharmacologic response and analgesic effects of opioids. Such interactions can lead to significant modifications to pain management in clinical settings. Therefore: The central hypothesis of this work is that the pathophysiological stressor peripheral inflammatory pain (PIP) and the pharmacological agent diclofenac modulate P-glycoprotein functional expression at the BBB. This hypothesis may be broken down further into two parts: 1) PIP induced changes in P-gp functional expression are mediated via changes in Pgp intracellular trafficking. 2) The non-steroidal anti-inflammatory drug Diclofenac, a drug commonly used to treat pain, modulates P-gp functional expression at the BBB thus decreasing morphine uptake into the CNS.

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

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

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.