Orientador: José Ricardo de Arruda Miranda / Banca: Cristina Helena dos Reis Serra / Banca: Oswaldo Baffa Filho / Banca: Raul César Evangelista / Banca: Eryvaldo Sócrates Tabosa do Egyto / Resumo: A administração oral de drogas é uma prática comum na terapia e as formas farmacêuticas sólidas são amplamente utilizadas. A variação no perfil de absorção ao longo do trato gastrintestinal (TGI) humano e a possibilidade de liberar drogas em diferentes regiões são os maiores desafios para o desenvolvimento de novos produtos. Desse modo, avaliar formas farmacêuticas sólidas in vivo fornece um entendimento mais profundo quando um efeito sistêmico ou local é desejado. Geralmente, estes estudos são realizados por meio da cintilografia e técnicas biomagnéticas. A Biosusceptometria de Corrente Alternada (BAC) é uma técnica que merece destaque por suas características, acurácia dos resultados obtidos e versatilidade. A BAC propiciou imagens do processo de desintegração de comprimidos tanto in vitro quanto no estômago humano, introduzindo outra perspectiva na análise desse processo. Os resultados também foram correlacionados com sucesso com aqueles obtidos por metodologias específicas, garantindo uma análise mais acurada dos parâmetros físicos envolvidos com a desintegração de comprimidos. A utilização da BAC permitiu avaliar a motilidade gastrintestinal e o processo de desintegração de cápsulas de hidroxipropilmetilcelulose (HPMC) revestidas no cólon humano. Além disso, também foi possível investigar a influência do estado prandial no esvaziamento gástrico e no trânsito gastrintestinal de um sistema multiparticulado magnético. Todos esses trabalhos fortaleceram a BAC como um método alternativo na pesquisa farmacêutica demonstrando seu potencial para avaliar diferentes processos, apesar das suas limitações. Sintetizando, a BAC é uma ferramenta valiosa, com a vantagem de ser livre de radiação e inócua aos voluntários, e vasta aplicabilidade na pesquisa farmacêutica, farmacológica e fisiológica. / Abstract: Oral administration is widely accepted route for drug delivery and solid dosage forms are commonly administered. The variation of absorption profiles along the human gastrointestinal tract (GIT) and the ability to target drugs by adequate dosage forms to distinct sites is the challenge in the pharmaceutical development of solid dosage forms. An understanding of the factors involved in drug absorption and how the gastrointestinal variables can interfere with this process is important to develop more reliable drug delivery systems. The performance of pharmaceutical dosage forms must be fully investigated in vivo to provide more reliable information when a local or systemic effect is desirable. Generally, in vivo investigation on the behavior of dosage forms has been made by using gamma‐scintigraphy and biomagnetic techniques. AC Biosusceptometry (ACB) deserves consideration due to its features, accuracy and versatility. By using ACB technique, it was possible to monitor the disintegration process through acquisition of magnetic images in vitro and in human stomach. The results also were successfully correlated with those obtained with standard methods which provided a more reliable analysis on the physical parameters involved in the disintegration process of tablets. ACB allowed evaluating the gastrointestinal motility and the disintegration of hydroxipropylmethylcellulose (HPMC) coated capsules in human colon. Moreover, it was possible to investigate the gastric emptying and gastrointestinal transit of a magnetic multiparticulate system under influence of prandial state. All these studies have contributed to establish the ACB as an alternative method for pharmaceutical research and, despite some limitations, it was feasible to evaluate different pharmaceutical processes. In summary, ACB is a radiation free and non‐invasive technique with wide applicability in pharmaceutical, physiological and pharmacological researches. / Doutor

L’agence européenne du médicament (EMA) stipule que les entreprises pharmaceutiques se doivent d’améliorer continuellement le contrôle de leur production afin de garantir la qualité des médicaments et préserver la santé des patients. Les outils analytiques classiques sont, par exemple, capables d’examiner l’intégralité d’un comprimé pharmaceutique pour contrôler la qualité et la quantité des substances actives utilisées et estimer leurs profils de libération dans l’organisme. Ils ne permettent cependant pas de cartographier la distribution des composés chimiques pourtant considérée comme un critère important pour la qualité du médicament. Des techniques d’imagerie chimique comme la MSI MALDI sont donc utilisées afin de déterminer par une analyse unique la répartition spatiale et la structure des composés constituant les médicaments. Toutefois, la MSI MALDI nécessite une préparation des échantillons relativement complexe et génère des données de grande taille difficilement exploitables. Ces caractéristiques, ainsi que l’absence de spectromètre de masse adapté à l’analyse de formes pharmaceutiques solides, complexifient la mise en place de la MSI MALDI au sein de laboratoires industriels. Les travaux réalisés durant cette thèse ont eu pour objectifs d’améliorer le protocole de préparation des échantillons, d’optimiser le système d’acquisition et de mettre en place les outils chimiométriques et informatiques nécessaires à l’analyse des images MALDI au sein de l’entreprise Technologie Servier. Les développements réalisés et les résultats obtenus ont finalement permis la résolution de problématiques inexplicables jusqu’alors par les techniques analytiques classiques. / European Medicines Agency (EMA) recommendations stipulate that pharmaceutical companies have to continually improve manufacturing efficiency to ensure drug product quality. The commonly used analytical tools provide information about drug substance quality and dosage or the drug release profile by dissolving the whole tablet. However these analytical tools are not able to highlight the distribution of chemical compounds contained in the tablet. This is why chemical imaging such as MALDI MSI are used to extract the spatial and spectral information from pharmaceutical solid dosage forms. This hyperspectral imaging technique needs complex sample preparation and generates huge dataset. These two features, as well as the lack of optimized mass spectrometers to study tablets, make difficult the implementation of the MALDI MSI in industrial laboratories. During this thesis, the sample preparation protocol has been improved, the mass spectrometer has been optimized to analyze tablets and chemometrics tools has been developed in order to implement MALDI MSI within Technologie Servier company.

Made available in DSpace on 2014-06-11T19:23:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-10-30Bitstream added on 2014-06-13T18:09:06Z : No. of bitstreams: 1 bolognesi_l_me_botib.pdf: 259849 bytes, checksum: d7d575323f591bd0006aeb8a07bc7b2b (MD5) / Universidade Estadual Paulista (UNESP) / A administração oral de fármacos é uma prática comum na terapia e as formas farmacêuticas sólidas são amplamente utilizadas. O conhecimento sobre o trânsito de cápsulas e comprimidos no trato gastrointestinal é incompleto. Desse modo, avaliar o trânsito esofágico de farmacêuticas sólidas fornece um entendimento mais profundo sobre os mecanismos que desencadeiam a esofagite induzida por fármacos. Geralmente, os estudos de trânsito esofágico são realizados por meio da cintilografia, manometria e técnicas biomagnéticas, como o SQUID (Dispositivos Supercondutores de Interferência Quântica) e a Biosusceptometria de Corrente Alternada (BAC). A BAC é uma técnica que merece destaque por suas características, acurácia dos resultados obtidos e versatilidade. O objetivo do trabalho foi investigar a influência do tipo e peso da forma farmacêutica no tempo de trânsito esofágico e na velocidade de transporte no esôfago, além de estabelecer parâmetros comparativos entre os métodos cintilográfico e biomagnético empregados, para validar a BAC no estudo de trânsito esofágico de formas farmacêuticas sólidas. Cada um dos seis voluntários que participaram do estudo deglutiu com 50 ml de água cápsulas e comprimidos com 0,5, 0,8 e 1,0 gramas de ferrita, na cintilografia e na BAC. Para o estudo cintilográfico, a radiomarcação das formas farmacêuticas foi feita com 99mTc. Os resultados obtidos mostraram que o tipo e o peso da forma farmacêutica não influenciaram significativamente o tempo de trânsito esofágico e a velocidade de transporte no esôfago, embora os resultados estatísticos apontem para uma variação significativa para um número maior de voluntários. Além disso, uma comparação entre as técnicas permitiu validar a BAC como um método biomagnético para avaliar o trânsito... / Oral administration is a common practice in drug therapy and the solid dosage forms are widely used. Knowledge about esophageal transit of tablets and capsules is incomplete since it have been reported a number of injuries related to drug-induced esophageal damage. Esophageal transit time may be evaluated by employing gammascintigraphy, manometry, and biomagnetic techniques as SQUID and AC Biosusceptometry (ACB). ACB is a non-invasive and radiation free technique which enough versatility for a number of studies related to the gastrointestinal behavior of solid dosage forms. The aim of this work was to investigate the influence of different dosage forms (hard gelatin capsules and tablets) on the esophageal transit time and transport velocity in the esophagus upon to establish a comparison between the Scintigraphy and Biosusceptometry and to validate the ACB as a tool for esophageal transit studies. Six volunteers have participated in the study and they swallowed capsules and tablets with 0.5g, 0.8g and 1.0g of ferrite together 50 ml of water. For scintigraphic study, the dosage forms were labeled with 99mTc. The results showed that the parameters evaluated could not be significantly influenced by the different dosage forms administered. However, it could be observed that the results pointed out to a decrease in the transit time measured for dosage forms with lower weight. We have shown that ACB allowed investigating the influence of dosage forms parameters on the esophageal transit time in healthy volunteers with high spatiotemporal resolution. In summary, this study has allowed introducing the ACB as an alternative technique to investigate the esophageal transit of pharmaceutical dosage forms to understand the factors which could contribute to drug-induced esophageal damages.

Yes / Detailed design of pharmaceutical tablets is essential nowadays in order to produce robust tablets with tailor-made properties. Compressibility and compactibility are the main compaction properties involved in the design and development of solid dosage forms. The data obtained from measured forces and displacements of the punch are normally analysed using the Heckel model to assess the mechanical behaviour of pharmaceutical powders. In this paper, we present a technique for shape modelling of pharmaceutical tablets based on the PDE method. We extended the formulation of the PDE method to a higher dimensional space in order to generate a solid tablet and a cuboid mesh is created to represent the tablet’s components. We also modelled the displacement components of a compressed PDE-based representation of a tablet by utilising the solution of the axisymmetric boundary value problem for a finite cylinder subject to a uniform axial load. The experimental data and the results obtained from the developed model are shown in Heckel plots and a good agreement is found between both. / Available in full text since 5th Feb 2013 following the publisher's embargo period.

Foram analisados 84 lotes de especialidades fitoterápicas de uso oral, na forma de cápsula, comprimido e pó, contendo 17 drogas vegetais, produzidas por 20 fabricantes e comercializadas em farmácias, drogarias, lojas de produtos naturais e supermercados da cidade de são Paulo. O confronto da apresentação comercial das mesmas em relação à legislação nacional, indicou que a minoria (15/84) atendeu a tais exigências, além de ter demonstrado total falta de padronização de qualidade pelos produtores, inclusive com ausência de definição e conceituação, enquadrando-as indistintamente como medicamentos alopáticos, homeopáticos, produtos dietéticos ou alimentos. Efetuou-se a quantificação de bactérias aeróbias mesófilas (forma vegetativa e esporulada) e de fungos (bolores e leveduras), através da técnica de tubos múltiplos, bem como a pesquisa de Escherichia coli e Salmonella sp. pela metodologia oficial internacional. A contaminação fúngica, predominantemente de bolores, foi inferior em relação à bacteriana aeróbia mesófila, pois o máximo detectado para aquela foi de 4,6 X 105, enquanto que para esta 5,1 X 109/g. A incidência fúngica com carga maior ou igual a 102/g foi de 34,5%, contra 53,6% da carga bacteriana vegetativa com 104/g ou mais e 45,2% da bacteriana esporulada, com o mesmo nível. A determinação do Número Mais Provável de Escherichia coli indicou incidência de 6,0% com a carga maior igual a 1,5 X 102/g. Houve estreita relação entre a carga bacteriana vegetativa total e o número de esporos, assim como a presença de patogênicos específicos em produtos altamente contaminados. Amostras sob a forma de pó foram as mais afetadas, seguidas de cápsulas e comprimidos. Pelo confronto dos dados encontrados, com os diversos padrões microbianos aplicados para medicamentos não estéreis de uso oral, para insumos e produtos fitoterápicos, o índice de aprovação variou de 29,8 a 94,0%. Mesmo frente ao padrão da FIP, a rejeição especialidades fitoterápicas analisadas foi da ordem de 59,5%. Em vista da qualidade sanitária de muitos destes produtos ser imprópria para o consumo, e após análise crítica dos vários padrões microbianos, discutiu-se a necessidade de implantação de especificações nacionais, ainda que a caráter provisório, sugerindo-se limites de tolerância para medicamentos fitoterápicos de uso oral. / 84 samples of phytotherapic products of oral solid dosage forms (capsules, tablets and powders) containing 17 different crude drugs and produced by 20 laboratories, marketed in drugstores, herborist\'s and supermarkets at são Paulo-Brazil were analysed with regard to legal marketing requirements, only 15 samples were in accordance. A complete lack of quality standard was attributed to the manufacturers, including indefinition as to the classification of products among allopathic or homeopathic pharmaceuticals or foods or dietetics. The total aerobic bacterial (vegetative and sporulated forms) and fungal (moulds and yeasts) contents were determined by multiple tube technique; moreover tests were carried out for Escherichia coli and Salmonella sp. by official international methods. The fungal contamination was predominantly of moulds and lower than the aerobic bacterial one. The maximum counts were 4,6 X 105 and 5,1 X 109/g, respectively, for fungi and bacteria. The frequency of samples with or more than 102/g fungi/g was 34,5% that for vegetative and sporulated bacterial counts with or more than 104/g was respectively, 53,6 and 45,2%. The incidence of Escherichia coli was about 6,0% with the highest level at 1,5 X 102/g. There was a tight relation between the vegetative and sporulated bacterial counts as well as the presence of specific pathogenic microorganisms in highly contaminated samples. The highest contamination occured in powders followed by capsules and tablets. Comparing our experimental data with the corresponding microbial standards for oral non sterile pharmaceuticals, crude drugs and phytotherapic products, the index of approval varied between 29,8 and 94,0%. Even by FIP\'s standards 59,5% of the phytotherapic specialties analysed had to be rejected. As many of these products showed innadequate sanitary quality for consumption, coupled to a critical analysis of the different microbial standards, the discution was raised about the necessity of establishing national specifications, even if provisional. Suggestions are made as to the contamination limits of oral phytotherapic pharmaceuticals.

Foram analisados 84 lotes de especialidades fitoterápicas de uso oral, na forma de cápsula, comprimido e pó, contendo 17 drogas vegetais, produzidas por 20 fabricantes e comercializadas em farmácias, drogarias, lojas de produtos naturais e supermercados da cidade de são Paulo. O confronto da apresentação comercial das mesmas em relação à legislação nacional, indicou que a minoria (15/84) atendeu a tais exigências, além de ter demonstrado total falta de padronização de qualidade pelos produtores, inclusive com ausência de definição e conceituação, enquadrando-as indistintamente como medicamentos alopáticos, homeopáticos, produtos dietéticos ou alimentos. Efetuou-se a quantificação de bactérias aeróbias mesófilas (forma vegetativa e esporulada) e de fungos (bolores e leveduras), através da técnica de tubos múltiplos, bem como a pesquisa de Escherichia coli e Salmonella sp. pela metodologia oficial internacional. A contaminação fúngica, predominantemente de bolores, foi inferior em relação à bacteriana aeróbia mesófila, pois o máximo detectado para aquela foi de 4,6 X 105, enquanto que para esta 5,1 X 109/g. A incidência fúngica com carga maior ou igual a 102/g foi de 34,5%, contra 53,6% da carga bacteriana vegetativa com 104/g ou mais e 45,2% da bacteriana esporulada, com o mesmo nível. A determinação do Número Mais Provável de Escherichia coli indicou incidência de 6,0% com a carga maior igual a 1,5 X 102/g. Houve estreita relação entre a carga bacteriana vegetativa total e o número de esporos, assim como a presença de patogênicos específicos em produtos altamente contaminados. Amostras sob a forma de pó foram as mais afetadas, seguidas de cápsulas e comprimidos. Pelo confronto dos dados encontrados, com os diversos padrões microbianos aplicados para medicamentos não estéreis de uso oral, para insumos e produtos fitoterápicos, o índice de aprovação variou de 29,8 a 94,0%. Mesmo frente ao padrão da FIP, a rejeição especialidades fitoterápicas analisadas foi da ordem de 59,5%. Em vista da qualidade sanitária de muitos destes produtos ser imprópria para o consumo, e após análise crítica dos vários padrões microbianos, discutiu-se a necessidade de implantação de especificações nacionais, ainda que a caráter provisório, sugerindo-se limites de tolerância para medicamentos fitoterápicos de uso oral. / 84 samples of phytotherapic products of oral solid dosage forms (capsules, tablets and powders) containing 17 different crude drugs and produced by 20 laboratories, marketed in drugstores, herborist\'s and supermarkets at são Paulo-Brazil were analysed with regard to legal marketing requirements, only 15 samples were in accordance. A complete lack of quality standard was attributed to the manufacturers, including indefinition as to the classification of products among allopathic or homeopathic pharmaceuticals or foods or dietetics. The total aerobic bacterial (vegetative and sporulated forms) and fungal (moulds and yeasts) contents were determined by multiple tube technique; moreover tests were carried out for Escherichia coli and Salmonella sp. by official international methods. The fungal contamination was predominantly of moulds and lower than the aerobic bacterial one. The maximum counts were 4,6 X 105 and 5,1 X 109/g, respectively, for fungi and bacteria. The frequency of samples with or more than 102/g fungi/g was 34,5% that for vegetative and sporulated bacterial counts with or more than 104/g was respectively, 53,6 and 45,2%. The incidence of Escherichia coli was about 6,0% with the highest level at 1,5 X 102/g. There was a tight relation between the vegetative and sporulated bacterial counts as well as the presence of specific pathogenic microorganisms in highly contaminated samples. The highest contamination occured in powders followed by capsules and tablets. Comparing our experimental data with the corresponding microbial standards for oral non sterile pharmaceuticals, crude drugs and phytotherapic products, the index of approval varied between 29,8 and 94,0%. Even by FIP\'s standards 59,5% of the phytotherapic specialties analysed had to be rejected. As many of these products showed innadequate sanitary quality for consumption, coupled to a critical analysis of the different microbial standards, the discution was raised about the necessity of establishing national specifications, even if provisional. Suggestions are made as to the contamination limits of oral phytotherapic pharmaceuticals.

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No. of bitstreams: 1 Dissertação - Jackeline de Souza Marinho.pdf: 2225410 bytes, checksum: 7a6f9be92271f2c88a3bc632cfead114 (MD5) Previous issue date: 2016-02-05 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Libidibia ferrea is an important plant species from Brazil, as pharmacology studies demonstrating potential therapeutic effects, such as anti-inflammatory and hypoglycemic associated with active substances, particularly in the stem bark and fruit. However, there are a few studies of the technological knowledge from transformation of the plant in a final dosage. Therefore, the aim of this study was to develop and assess the feasibility of obtaining solid dosage forms containing high spray dried product from fruit Libidibia ferrea. The plant material was collected, processed and characterized according to the quality control parameters. The spray dried extract (PSA) was produced from the optimization of the drying process of the extraction solution, which aimed to improve the yield and the physicochemical characteristics of the powder. The improved PSA was used to produce granulates, evaluating the efficiency of the method by wet and suitable granulating agent. The granules produced were characterized from a technological point of view and used as an intermediate for handling capsules. The influence of different flow regulators in the formulation of capsules (magnesium stearate, sodium lauryl sulfate and colloidal silicon dioxide) was studied by means of tests recommended by the Brazilian Pharmacopoeia (weight average, disintegration and liodisponibility). In order to evaluate the chemical stability during the production process it was determined content of total polyphenols in all process steps. The results obtained showed that the raw material is within the required quality standards and can be used for the production of pharmaceutical forms. The polyphenols content has not changed significantly during the drying process of the extraction solution, indicating that there was no degradation of constituents. The Eudragit E® proved to be a good granulation agent at a concentration of 15%, resulting in somewhat friable granules (1.68%) and high yield (80.6%) granulating the wet method. The presence of the flow regulators in the formulations did not cause significant differences in accordance with the tests performed demonstrate that the use thereof does not imply changes which impair the quality and efficacy of the product. The dissolution profile showed that the capsules did not suffer total dissolution (up 78.676%), which may be associated with several factors related to the formulation, dissolution medium, among others. Thus, the present study demonstrated that it is feasible the production of solid dosage forms, such as granules and capsules from the PSA given plant species, however further studies are still needed, particularly for the determination of chemical markers in order to analyze the stability of analytical method. / Libidibia ferrea é uma espécie vegetal de destaque no Brasil, uma vez que estudos farmacológicos demonstram potenciais efeitos terapêuticos, tais como anti-inflamatório e hipoglicemiante, atribuídos a substâncias ativas presentes, principalmente, na casca do caule e nos frutos. No entanto, os conhecimentos tecnológicos que propiciam a transformação da planta em uma forma farmacêutica final ainda são bastante incipientes. Por conseguinte, o objetivo desse estudo foi desenvolver e avaliar a viabilidade de obtenção de formas farmacêuticas sólidas contendo alto teor de produto seco por aspersão de frutos de Libidibia ferrea. O material vegetal foi obtido, processado e caracterizado de acordo com os parâmetros de controle de qualidade. O produto seco por aspersão (PSA) foi produzido a partir da otimização do processo de secagem da solução extrativa, que teve por finalidade melhorar o rendimento e as características físico-químicas do pó. O PSA otimizado foi utilizado para a produção de granulados, avaliando-se a eficiência do método por via úmida e o agente de granulação adequado. Os granulados produzidos foram caracterizados do ponto de vista tecnológico e utilizados como produto intermediário para a manipulação das cápsulas. Foi estudada a influência de diferentes reguladores de fluxo na formulação das cápsulas (estearato de magnésio, lauril sulfato de sódio e dióxido de silício coloidal) por meio de ensaios preconizados pela Farmacopeia Brasileira (peso médio, desintegração e liodisponibilidade). A fim de avaliar a estabilidade química durante o processo de produção, determinou-se o teor de polifenois totais em todas as etapas do processo. Os resultados obtidos permitiram verificar que a matéria-prima atende aos padrões de qualidade exigidos, podendo ser utilizada para a produção de formas farmacêuticas. O teor de polifenois não sofreu grandes alterações durante o processo de secagem da solução extrativa, indicativo de que não houve degradação de constituintes. O Eudragit E® demonstrou ser um bom agente de granulação na concentração de 15%, originando granulados pouco friáveis (1,68%) e de elevado rendimento (80,6%) pelo método de granulação por via úmida. A presença dos reguladores de fluxo nas formulações não ocasionou diferenças significativas de acordo com os ensaios realizados, demonstrando que a utilização destes não implica em alterações que comprometam a qualidade e eficácia do produto. O perfil de dissolução demonstrou que as cápsulas não sofreram dissolução total (máximo 78,676%), fato que pode estar associado a diversos fatores relacionados à formulação, meio de dissolução, entre outros. Dessa forma, o presente estudo demonstrou que é viável a produção de formas farmacêuticas sólidas, como granulados e cápsulas, a partir do PSA da dada espécie vegetal. No entanto, estudos mais aprofundados ainda são necessários, principalmente quanto ao doseamento de marcadores químicos, a fim de analisar a estabilidade por método analítico.

Thesis (M. Pharmacy ((Pharmaceutics)) -- University of Limpopo, 2022 / According to the biopharmaceutical classification system, Clarithromycin is considered a class II molecule with low solubility. Poorly soluble drugs result in low bioavailability. Various techniques have been studied to improve the solubility of drugs and subsequently bioavailability. Of these techniques, preparation of amorphous form is the preferred method because it is a more effortless and convenient way to improve the aqueous solubility and dissolution of poorly water soluble drugs. The only disadvantage of amorphous materials is that they are less thermodynamically stable and can recrystallize during processing and storage. Aim: The aim of this study is to prepare amorphous form of clarithromycin to improve its solubility, dissolution rate, and, subsequently, bioavailability. Methods: In this study, preparation of amorphous form of clarithromycin was conducted using the quench cooling method in which the purchased anhydrous crystalline clarithromycin was spread on an aluminum foil and heated to a melting point (217˚C - 220˚C) and then rapidly cooled. Various techniques were conducted to characterize the prepared amorphous clarithromycin, and these include Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and X-Ray Powder Diffraction (XRPD). In addition, tablets were formulated using the amorphous clarithromycin mixed with selected excipients from compatibility studies, and in vitro dissolution and stability studies were conducted over a period of 6 months. Results: The DSC thermogram results confirmed that the material prepared using the quench cooling process is an amorphous solid-state. Furthermore, the XRPD confirmed an amorphous solid-state with scattering halo peaks. The FTIR also depicted some broader and lower intensity peaks that indicated a formation of an amorphous material. The dissolution rate of amorphous clarithromycin tablets improved by more than 30% when compared to commercial crystalline clarithromycin tablets. The study revealed a drop in dissolution rate at months 3 to 6 under accelerated conditions due to recrystallization. The 6 monthly stability study at long term conditions showed no change in the integrity of the tablets and their contents. Conclusion: As indicated by the study, it can be concluded that the amorphous clarithromycin remained stable during processing and storage under long-term stability for 6 months. Furthermore, based on dissolution results, it can be concluded that amorphous solids have an improved dissolution rate. / Medical Research Council CHIETA

Hot-melt extruded solid dispersion technique is increasingly employed to improve the solubility of poorly water-soluble drugs. The technique relies on the enhanced solubility of the amorphous form of the drug compared to its crystalline counterpart. These systems however are thermodynamically unstable. This means that the drug crystallises with time. Therefore, efforts to measure the stability of these systems over the life span of the product are crucial. This study focused on investigating the use of Hansen Solubility Parameters to quantify polymer-drug interaction and to predict the stability of solid dispersions. This was achieved through a systematic review of hot-melt extruded solid dispersion literature. The study also investigated the use of a combined mechanical and rheological model to characterise the physicochemical and release behaviour of three solid dispersion immediately after preparation and after storage for one month at 40oC or three months at room temperature. Results revealed that the total solubility parameter |ΔбT| was able to predict the stability of the systems for more than 4 months using a cut-off point of 3 MPa-1 with a negative predictive value of 0.9. This was followed by ΔбD with a cut-off point of 1.5 MPa- 1. Moreover, Dynamic Mechanical Analyser and shear rheometry data were shown to be more sensitive than Differential Scanning Calorimetry, Powder X-Ray Diffraction, Scanning Electron Microscope and Fourier Transform Infrared in detecting crystallisation and the interaction between the drug and the polymer. The Dynamic Mechanical Analyser data were consistent with the dissolution behaviour of the samples when comparing the freshly prepared samples with those after storage. The results highlight the need for a unified characterisation approach and the necessity of verifying the homogeneity of mixing during the extrusion process.

Magister Pharmaceuticae - MPharm / Sutherlandia frutescens (tribe Galegeae, Fabaceae), is a popular medicinal plant traditionally used in South Africa. In 2000, a company called Phyto Nova (Pty) Ltd. initiated large-scale cultivation and contract manufacturing of tablets, made from the powdered herb (i.e. thin stems and leaves). Most of these commercial Sutherlandia solid dosage forms are made from the dried leaf powder but recently a new product, viz. Promune™ capsules, made from a freeze-dried aqueous extract, came on the market and was claimed to be “better” as it mimics the traditional tea. However, the pharmaceutical quality and stability of these preparations have not yet been investigated. The objectives of this study were firstly, to develop a validated stability-indicating HPLC assay for sutherlandioside B (SU-B); secondly, to compare the SU-B levels in the two commercially available Sutherlandia products viz, the Phyto Nova Sutherlandia SU1™ tablet and the Promune™ capsule, and, thirdly, to determine the effect of elevated temperature and humidity as well as acid hydrolysis on the SU-B levels in these two products. / South Africa