The focus in the field of machine learning has increasingly shifted towards data-centric approaches, recognizing that the quality of data is crucial for the effectiveness of the models developed. One significant challenge that can degrade data quality is the presence of outliers. Therefore, this study investigates the impact of various outlier detection algorithms on the performance of machine learning models applied to QSAR datasets. Utilizing methods such as Isolation Forest (IF), Local Outlier Factor (LOF), and One-Class Support Vector Machine (OCSVM), the aim was to explore these methods and evaluate them, identify potential outliers, and assess their influence on model predictions. The study incorporated both synthetic data and real-world datasets, including those obtained from a pharmaceutical company and benchmark datasets. The methodology involved preprocessing the data, applying outlier detection algorithms, and evaluating the models using traditional metrics like Mean Squared Error (MSE) and conformal prediction for uncertainty estimation. Results indicated that no major improvements were observed using the different algorithms and that excessive data removal led to a decline. While OCSVM showed inconsistent performance across different datasets, LOF demonstrated promising potential as a method worth further investigation. This study has even highlighted different challenges including high dimensionality, the need for hyperparameter tuning, and the limitations of current outlier detection methods. It also underscores the complexity of outlier detection in QSAR data and suggests directions for future research to improve model robustness and accuracy.

In the world of business there are few industries that have challenged and overcome the world's economic troubles, that industry is pharmaceuticals. This industry has managed to stay one of the most lucrative businesses in the world because of its ability to adapt and the marketing skill to boost profits. This is achieved primarily through the pharmaceutical company's pharmaceutical representatives. These salespeople visit doctors and make them aware of their company's products and benefits. Since 1997, pharmaceutical companies have approached their business in a new way. The FDA approved Direct-to-Consumer advertising seen on T.V. and various other forms of media allowed these pharmaceutical companies to reach a whole new consumer. This reached their ultimate consumer, which had not been targeted before. As will be seen in this research, this advertising has had an affect on its target, whether that be the patient, the doctor, or the pharmaceutical salesperson. This is considered a pilot study because it is the beginning of research that will be done on the effects of Direct-to-Consumer advertising on the pharmaceutical salesperson's relationship and marketing approach with the doctor. This study was designed to research and determine the effects, if any, that this new form of advertising has had on how these pharmaceutical reps and their techniques have adjusted to this additional factor. The purpose is to determine if this advertising has had any degree of affect on the pharmaceutical rep and if their parent company has adapted.

Background: In health status assessment, patient-reported outcome (PRO) measures are tools used to elicit important and measurable information from patients to better understand the impact of health conditions on their lives. Such impacts are considered latent constructs, or variables that cannot be observed or measured directly. Instruments intended to assess latent constructs must satisfy certain development, psychometric, and scaling standards through the generation of both qualitative and quantitative evidence to demonstrate the adequacy of its measurement properties. Health-related quality of life (HRQOL), or the subjective perception of health, is a core concept within the field of PROs. The Short Form 36 (SF-36) is one of the most commonly used PROs used to assess health-related quality of life (HRQOL).Objectives: To provide a better understanding of the performance and dimensionality of the SF-36 version 2 in a cross-sectional sample of patients with multiple sclerosis (MS) on an item, subscale, and higher-order factor structure level using different measurement methods grounded in classical test theory (CTT), factor analysis, and item response theory (IRT).Methods: This was a post hoc analysis of a cross-sectional dataset. Patients with MS were recruited to participate in an online survey asking a variety of questions related to their health and treatment seeking behaviors. The SF-36 was one of the questionnaires included in the survey. Items and individual subscales were evaluated using a multi-trait/multi-item correlation matrix to assess item-to-subscale relationships, including item discriminant validity with other subscales. Unidimensionality for select SF-36 subscales was assessed through confirmatory factor analysis (CFA). Internal consistency reliability (Cronbach's alpha) was evaluated for each subscale. Patient-reported disability, depression, and current symptom exacerbation status were evaluated relative to SF-36 subscale scores to assess convergent validity, discriminant validity, and known-groups validity. Higher-order factor models of the SF-36 were tested to evaluate dimensionality of the instrument, including a two-factor second-order factor model, a bifactor model, and a statistical comparison between the bifactor model and its corresponding nested model. Unidimensionality was further evaluated through the use of graded response IRT models. The relative fit of traditional versus discrimination-constrained models was tested using a -2 loglikelihood ratio test, followed by an evaluation of item-level properties for fit (S-X² statistics), local dependence, and further assessment of model parameters (discrimination parameters, location parameters, option response functions, and test information curves). Person location parameters were also estimated to compare scale information to the location of patients along the latent construct. Results: A total of 1,052 respondents completed the survey. Unidimensionality of individual subscales evaluated via CFA all had confirmatory fit indices (CFI)>0.90, butroot mean square error of approximation [RMSEA] values all exceeded 0.08. All IRT graded response models showed a statistically significant improvement in model fit when item discrimination was freely estimated. Each subscale from the IRT models had at least one mis-fitting item across all unidimensional scales tested (S-X² p-value>0.05), and nearly all subscales tested showed item pairs with signs of local dependence. Cronbach's alpha was>0.80 for all subscales except for General Health [GH] (alpha = 0.78). SF-36 subscales most closely related to physical aspects of health status had the strongest relationship to disability status (physical functioning [PF], r = -0.82, and role physical [RP], r = -0.57). Subscales more closely related to mental health had the largest effect sizes between patients with versus without depression (0.88 for mental health [MH] subscale) and the smallest effect sizes between patients reporting currently experiencing versus not experiencing an exacerbation of their symptoms (0.48 for role emotional [RE]subscale). Both CFA and IRT analyses showed lack of compelling evidence supporting unidimensionality upon combining items from the PF, RP, bodily pain [BP], and GH subscales to form the Physical-21, and upon combining items from the VT, role emotional (RE), social functioning (SF), and MH subscales to form the Mental-14. Higher-order factor models showed good model fit, with CFI>0.90 in all cases and lower RMSEA values than seen for the individual subscales (0.077 to 0.107). The bifactor model fit significantly better than its nested second-order version, however, the best-fitting (i.e., highest CFI and lowest RMSEA) higher-order factor model was the preliminary first-order model with eight first-order factors consistent with the eight subscales of the SF-36 (CFI=0.996, RMSEA=0.077, X² = 3872.14, p<0.001). Conclusions: The SF-36 version 2 performed well when evaluated within the CTT framework, but both CFA and IRT methods revealed several limitations at the item and factor level across all subscales, due to item wording (i.e., positive versus negative), items not being sufficiently related to its latent construct, and local dependence of items within and across subscales. The appropriateness of equal weighting of responses to produce a single summary score for each subscale, as well as their further aggregation into the Physical Component Summary and Mental Component Summary scores should be reevaluated.

This thesis is focused on a private brand of food supplements called IPC COMPLEX. IPC COMPLEX is produced by company Pharmaceutical Corporaration, a.s., and has been freshly introduced in the Czech market. The paper aims to assess production costs and sales in 2013, to calculate mark-up, margin and total gross profit. A comparison of sales with the rival products in each category follows. The evaluation is also subjected to meet the balance sheet established before entering the market. Moreover, the aims of the management are assessed together with return on investments and presumed positive impact on management of the society. The research focuses on monitoring the private brand. The data - provided exclusively for this research, were collected in 2013 and represent all 42 pharmacies owned by the chain IPC in the Czech Republic. The thesis tries to evaluate economic impacts of private brand on the pharmaceutical market for food supplements. These consequences are compared with impacts of private brands in other fields. Generally, the impact is believed to be positive and to be beneficial for powerful retail chains. Despite the minor failures, this thesis proved that a private brand of food supplements can have the very same positive impact on the Czech pharmaceutical market. The private brand has...

The increase in use and distribution of pharmaceuticals on a global scale has caused pharmaceuticals to play an integral role in the notions of quality of health. This study is concerned with how Western medication is transacted and interpreted in explicit and implicit contrast to the other context. I observe the commercial trade of medicines, specifically the effects of regulation of pharmaceutical drug trade in a suburb of Johannesburg (Yeoville) a low income area where many migrant groups have found long and short term refuge. A Policing and Mobility Project (Hornberger & Cossa 2010) centred on tracing paths of medication and the level of policing thereof in Johannesburg revealed that clandestine sale of medication occurs in the suburb’s local market. This prompted a comparison between the formal and informal pharmaceutical trade spaces. Simon (a pharmacist) and Teresa (a former nurse turned market trader) sell pharmaceutical drugs in seemingly contrasting contexts. Despite their expertise in health care, Simon and Teresa were flung to opposite ends of the trade spectrum by regulation. In the weeks I spent with Teresa and Simon it became abundantly clear that the spaces which had been initially presented as the opposite of one another may have had a few layers of common ground. At first it seems as though only regulation has the ability to produce authority, trust and accountability. But later it becomes evident that such aspects can be reproduced through manipulation of everyday practices. Roger Cotterrell’s (1999) interpretation of Emile Durkheim’s view of the law as a ‘Social Fact’ (1999:9), demonstrates how the collective experience of regulation (an aspect of the law) affects the individual. But De Certeau (1984) claims that the same individual can tacitly undermine this collective experience (the dominant form) through everyday practices. The findings suggest that the assumed roles of regulated and unregulated pharmaceutical trading spaces are not as static as they appear. The study concluded that authority, trust and accountability can be reproduced outside of regulation. And secondly thus the formal and informal trade of pharmaceuticals in Yeoville have more in common than perceived since both Simon and Teresa, had authority in health, their customer’s trust and loyalty and were accountable within the trade.

A profissão farmacêutica vive momento de busca de novas práticas baseadas na atenção farmacêutica. O objetivo deste estudo foi conhecer a prática profissional de farmacêuticos que atuavam em farmácias com ênfase em atividades relacionadas à prática da atenção farmacêutica. Material e métodos. Trata-se de um estudo descritivo tipo survey transversal; os dados foram coletados em entrevistas com farmacêuticos do município de Jundiaí/SP. Resultados. Entrevistou-se 93 farmacêuticos, sendo a maioria jovem (31,7 anos em média), do sexo feminino (62,4%), graduada em instituições privadas (90,1%) e não proprietária do estabelecimento (86,0%); desenvolviam na farmácia atividades administrativas, técnicas e de atenção ao usuário, em especial, orientações e dispensação de medicamentos; 67,7% acompanhavam o tratamento farmacoterapêutico dos usuários, mas sem registro de informações, e 77,8% já haviam detectado algum problema com a medicação. Muitos farmacêuticos (91,4%) consideravam necessário realizar um trabalho de maior proximidade com os usuários, porém apontaram como principais dificuldades a falta de: tempo, apoio dos proprietários, interesse dos usuários e conhecimento. A compreensão que 62,3% tinha sobre atenção farmacêutica estava relacionada à orientação e ao atendimento dispensados. Conclusões. A prática da atenção farmacêutica, como preconizada na literatura, não foi observada entre os entrevistados. Estudos futuros para conhecer como os farmacêuticos realizam suas atividades são importantes ao aprimoramento dos serviços farmacêuticos e melhorar a compreensão sobre atenção farmacêutica poderá ajudar na sua implementação. / The pharmaceutical profession is searching for new practices based on pharmaceutical care. The purpose of this study was to get to know the professional practice of the pharmacists who worked in pharmacies, with emphasis placed on the activities related to the pharmaceutical care practice. Material and methods. This is a transversal survey descriptive study; the data were collected among pharmacists of the municipality of Jundiaí/SP. Results. In total, 93 pharmacists were interviewed, most of whom were young (31.7 years of age on average), female (62.4%), private institution graduates (90.1%), and were not pharmacy owners (86.0%); at the pharmacy, they carried out administrative, technical, and attention to patient activities, particularly providing guidance and dispensing medications; 67.7% followed-up on their patient's pharmacotherapeutic treatment, but did not record any information regarding it, while 77.8% had already detected some type of problem with medications. Many pharmacists (91.4%) considered it necessary to work more closely with their patients; however, the main difficulties they mentioned to in order to do so included the lack of time, pharmacy owner support, patient interest, and knowledge. The understanding 62.3% had about pharmaceutical care was related to providing guidance and customer service. Conclusions. The pharmaceutical care practice among the interviewees was not observed as in the literature. Future studies aimed at getting to know how the pharmacists perform their activities are important in order to improve the pharmaceutical services and to improve the understanding about pharmaceutical care can help implanting.

A hipertensão arterial sistêmica é uma doença crônica em que a pressão arterial do indivíduo permanece acima de 140/90 mmHg. Ela afeta aproximadamente 70 milhões de pessoas nos EUA e 1 bilhão de pessoas em todo o mundo (ONG et al, 2007). Essa enfermidade pode levar a complicações, das quais se pode destacar o infarto agudo do miocárdio e o acidente vascular cerebral. Estudos têm demonstrado que a atenção farmacêutica pode auxiliar na obtenção de resultados clínicos importantes, como a redução da pressão arterial (ERICKSON; SLAUGHTER; HALAPY, 1997; ZILLICH et al. 2005), entretanto os recursos limitados impedem a garantia de um atendimento farmacêutico adequado a todo paciente que utiliza medicamentos. Diante do exposto, o presente estudo tem como finalidade desenvolver e avaliar um formulário para a seleção de pacientes hipertensos e inclusão destes junto a um serviço de AtenFar, bem como analisar a efetividade deste durante o período de acompanhamento e após a alta desses pacientes. Esse estudo foi dividido em quatro fases, sendo elas: fase de desenvolvimento do INSAFHAS, fase de seleção, fase de acompanhamento, e fase de alta. Em adição, os sujeitos da pesquisa foram divididos de acordo com a pontuação obtida no instrumento (G1 - maior pontuação, G2- menor pontuação) e os usuários de cada grupo foram randomizados em outros dois grupos, sendo eles, Controle (C) e Experimental (E). Com isso, obteve-se um total de quatro grupos (G1C, G1E, G2C, G2E), sendo que os sujeitos dos grupos experimentais foram incluídos em um serviço de atenção farmacêutica e acompanhados em atendimentos mensais por doze meses. Observou-se que os sujeitos do grupo 1 apresentavam idade superior, menor escolaridade, valores superiores de pressão arterial sistólica e de glicemia de jejum e menor conhecimento relativo ao tratamento medicamentoso. Verificou-se ainda, ao final da fase de acompanhamento, redução da pressão arterial no G1E e redução no IMC, aumento da adesão ao tratamento medicamentoso e do conhecimento relativo ao tratamento medicamentoso no G2E. Na fase de alta houve aumento da pressão arterial em todos os grupos, porém não foram observadas evidências científicas de que esse aumento era significativo. Sendo assim, pode-se concluir que o instrumento elaborado foi adequado para a seleção de indivíduos para um serviço de atenção farmacêutica, e que o mesmo promoveu melhoras clínicas nos hipertensos. Porém novos estudos a respeito da alta dos usuários precisam ser realizados. / Hypertension is a chronic disease in which blood pressure remains above 140/90 mmHg. It affects approximately 70 million people in the United States and 1 billion people worldwide (ONG et al, 2007). This disease may lead to complications, such as, we can highlight acute myocardial infarction and stroke. Studies have shown that pharmaceutical care can help to achieve important clinical outcomes, such as reduced blood pressure (ERICKSON; SLAUGHTER; HALAPY, 1997; ZILLICH et al 2005). However limited resources hinder the assurance of an appropriate pharmaceutical service to every patient who uses drugs. Therefore this study aims to develop and evaluate a form for selection of hypertensive patients and inclusion of these patients into a pharmaceutical care service as well as analyzing the effectiveness of this service during the follow-up period and after discharge. This study was divided into four phases, namely: development of the INSAF-HAS phase, selection phase, follow-up phase, and discharge phase. Subjects were divided according to the score obtained in the form (G1 - highest score, G2 - lowest score). Patients in each group were randomized into two groups, namely, Control (C) and Experimental (E), so we obtained a total of four groups (G1C, G1E, G2C, G2E). By the way subjects in experimental groups were included in a pharmaceutical care service and followed-up at monthly visits for twelve months. We found higher age, lower education, higher systolic blood pressure and fasting glucose, slightest knowledge on the medical treatment in Group 1 than Group 2. At the end of follow-up phase it was found lowering blood pressure in G1E and reduction in BMI, increased adherence to drug therapy and knowledge relating to drug therapy at G2E. In the discharge phase there was increased BP in all groups, but evidence was not observed that this increase was significant. Thus, it could be conclude that the instrument was appropriate for screening individuals for a pharmaceutical care service, and the pharmaceutical care service promoted clinical improvement in hypertensive patients. Even so new studies about the discharge are required.

O polimorfismo é um fenômeno relativamente comum entre os compostos farmacêuticos, e um dos principais problemas na produção e desenvolvimento de medicamentos. Sua presença pode acarretar prejuízos para a saúde da população e forte impacto econômico para as indústrias farmacêuticas ao influenciar diretamente nas propriedades mecânicas e biofarmacêuticas de insumos e produtos acabados. A investigação de polimorfismo associado aos oxicans, grupo pertencente à classe dos fármacos anti-inflamatórios não esteróides (AINEs), sofreu um incremento nos últimos anos, e para o fármaco tenoxicam relata-se a existência de quatro formas polimórficas na literatura. O objetivo deste trabalho foi caracterizar a presença de diferentes formas polimórficas de tenoxicam em insumos farmacêuticos ativos e formulações farmacêuticas orais e avaliar a influência sobre a dissolução in vitro. Com base na literatura, a análise inicial com a substância química de trabalho (SQT) demonstrou padrão difratométrico forma III. Diferentes condições para formação de formas polimórficas de tenoxicam foram aplicadas conforme Cantera et al. (2002), contudo, os diferentes processos de preparação de polimorfos do tenoxicam não conduziram a modificações na estrutura cristalina original da SQT. Dados complementares foram obtidos através da espectrofotometria no IV e DSC, que indicaram a inexistência de modificações no espectro original e ausência de eventos térmicos atípicos. A caracterização dos insumos farmacêuticos do tenoxicam, provenientes de diferentes fornecedores, por IV, DRX e perfil de dissolução indicou presença da estrutura cristalina (forma III), sem apresentar diferenças significativas entre os perfis de dissolução in vitro. As especialidades farmacêuticas do tenoxicam disponíveis no mercado nacional, ao serem submetidas à análise por DRX, também apresentaram estruturas cristalinas forma III. Apesar de ocorrer perfis de dissolução diferentes entre as formulações, estas não apresentaram comprometimento em sua qualidade. Contudo, muitas vezes as transformações pós-processamento podem induzir a alterações na estrutura cristalina e por consequência, problemas biofarmacêuticos. Tal fato demonstra a importância do estudo do polimorfismo, ao avaliar e correlacionar a presença de estruturas cristalinas com alterações na qualidade e desempenho de insumos e produtos farmacêuticos. / Polymorphism is a relatively common phenomenon among pharmaceutical compounds, and one of the main problems in producing and developing drugs. Its presence may harm people’s health and have a strong economic impact on the pharmaceutical industries by directly influencing the mechanical and biopharmaceutical properties of inputs and finished products. The investigation of polymorphism associated with oxycans, a group belonging to the class of non-steroidal anti-inflammatory drugs (NSAIDs), has grown in recent years, and it is reported that there are four polymorphic forms for tenoxycam the literature. The purpose of this study was to characterize the presence of different polymorphic forms in active pharmaceutical inputs and oral pharmaceutical formulations and evaluate their influence on in vitro dissolution. Based on the literature, the initial analysis with the reference standard showed a form III diphractometric pattern. Polymorphic forms of tenoxycam were prepared according to Cantera et al. (2002), but the different preparation processes of tenoxycam polymorphs did not lead to modifications of the original crystalline structure of the reference standard. Complementary data were obtained by spectrophotometry in IV and DSC, indicating that there were no modifications in the original spectrum and no atypical thermal events. The characterization of the pharmaceutical inputs of tenoxycam, from different suppliers, as IV, DRX and dissolution profile indicated the presence of a crystalline structure (Form III), without presenting significant differences between the in vitro dissolution profiles. The pharmaceutical specialties of tenoxycam available on the national market, on being analyzed by DRX also presented crystalline structures Form III. Although there was different dissolution profiles between the formulations, they showed no impairment in their quality. However, often the post-processing transformations can induce alterations in the crystalline structure and, consequently, biopharmaceutical problems. This shows the importance of the study of polymorphism with the evaluation and correlation of the presence of crystalline structures with alterations in the quality and performance of pharmaceutical inputs and products.

A profissão farmacêutica vive momento de busca de novas práticas baseadas na atenção farmacêutica. O objetivo deste estudo foi conhecer a prática profissional de farmacêuticos que atuavam em farmácias com ênfase em atividades relacionadas à prática da atenção farmacêutica. Material e métodos. Trata-se de um estudo descritivo tipo survey transversal; os dados foram coletados em entrevistas com farmacêuticos do município de Jundiaí/SP. Resultados. Entrevistou-se 93 farmacêuticos, sendo a maioria jovem (31,7 anos em média), do sexo feminino (62,4%), graduada em instituições privadas (90,1%) e não proprietária do estabelecimento (86,0%); desenvolviam na farmácia atividades administrativas, técnicas e de atenção ao usuário, em especial, orientações e dispensação de medicamentos; 67,7% acompanhavam o tratamento farmacoterapêutico dos usuários, mas sem registro de informações, e 77,8% já haviam detectado algum problema com a medicação. Muitos farmacêuticos (91,4%) consideravam necessário realizar um trabalho de maior proximidade com os usuários, porém apontaram como principais dificuldades a falta de: tempo, apoio dos proprietários, interesse dos usuários e conhecimento. A compreensão que 62,3% tinha sobre atenção farmacêutica estava relacionada à orientação e ao atendimento dispensados. Conclusões. A prática da atenção farmacêutica, como preconizada na literatura, não foi observada entre os entrevistados. Estudos futuros para conhecer como os farmacêuticos realizam suas atividades são importantes ao aprimoramento dos serviços farmacêuticos e melhorar a compreensão sobre atenção farmacêutica poderá ajudar na sua implementação. / The pharmaceutical profession is searching for new practices based on pharmaceutical care. The purpose of this study was to get to know the professional practice of the pharmacists who worked in pharmacies, with emphasis placed on the activities related to the pharmaceutical care practice. Material and methods. This is a transversal survey descriptive study; the data were collected among pharmacists of the municipality of Jundiaí/SP. Results. In total, 93 pharmacists were interviewed, most of whom were young (31.7 years of age on average), female (62.4%), private institution graduates (90.1%), and were not pharmacy owners (86.0%); at the pharmacy, they carried out administrative, technical, and attention to patient activities, particularly providing guidance and dispensing medications; 67.7% followed-up on their patient's pharmacotherapeutic treatment, but did not record any information regarding it, while 77.8% had already detected some type of problem with medications. Many pharmacists (91.4%) considered it necessary to work more closely with their patients; however, the main difficulties they mentioned to in order to do so included the lack of time, pharmacy owner support, patient interest, and knowledge. The understanding 62.3% had about pharmaceutical care was related to providing guidance and customer service. Conclusions. The pharmaceutical care practice among the interviewees was not observed as in the literature. Future studies aimed at getting to know how the pharmacists perform their activities are important in order to improve the pharmaceutical services and to improve the understanding about pharmaceutical care can help implanting.

引子: 共晶技術和納米沉澱技術於近年被廣泛討論能改進藥物性質和提高體內性能。本論文研究旨在將該兩種技術嘗試應用於五種模型藥物中，分別是薑黃素(CUR)，氟比洛芬(FLU)，布洛芬(IBU)，酮洛芬(KET) 和環氧洛芬(LOX)。這些藥物均難溶於水，擁有較差機械性質，相對高的親油性和潛在治療腦退化症的功用。在共晶技術中，藥物將會與煙酰胺(NCT)先溶於在溶劑中，透過蒸發以誘發共晶產生。另一方面，瞬時納米沉澱(FNP)技術會將藥物溶液(包含穩定劑)與反溶劑在封閉衝擊射流混合器(CIJM)或多入口渦旋混合器(MIVM)快速混合，生成納米藥物。 / 方法: 將藥物和NCT溶於乙醇中，應用旋轉蒸發或簡單蒸發生成共晶。透過不同的檢測方法，包括X射線衍射，差示掃描量熱法，熱重分析，吸濕分析，傅立葉變化紅外線光譜，特性溶出速率量度法和壓實分析將共晶檢定。另一方面，利用CIJM或MIVM，藥物在不同的混合速率，溶劑性質，聚乙二醇-聚乳酸(穩定劑)分子重量或藥物對聚合物比的工藝環境下載入於納米粒子中。生產出來的納米藥物會利用動態光散射測定粒徑; 電泳光散射法測定zeta電位; 掃描電子顯微鏡和原子力顯微鏡測定粒子形貌和其表面性質; X-射線光電子能譜測定表面成分; 高效液相色層分析測定載藥量和包封率。 / 結果: 利用旋轉蒸發，高純度的1:1 IBU-NCT 和FLU-NCT 的共晶能成功生成，但KET-NCT和LOX-NCT 共晶則不能獲得。低純度的CUR-NCT 共晶可根據相同技術取得。相比原來藥物而言，IBU-NCT 和FLU-NCT 共晶均有較好的機械性質，抗吸水性和溶解速度。而在FNP研究中，証實了混合速率，溶劑性質，聚乙二醇-聚乳酸(穩定劑)分子重量或藥物對聚合物比均對生產出來的納米粒子的粒徑有重要影響。另外，納米粒子的穩定性可籍添加輔助穩定劑(如PVA)大幅提高。XPS分析証實輔助穩定劑能與在粒子表面的聚乙二醇起相互作用，更佳地保護粒子。而在一系列對四種不同的洛芬藥物的實驗中，多次線性回歸分析指出三種有關藥物的溶液性質(即溶解度，分配係數和酸度系數)會對生成的納米粒子的粒徑和包封率有顯著影響。 / 結論: 將IBU和FLU與NCT結成共晶能同時提高其機械性質，抗吸水性和溶解速度。而在FNP中，優化不同工藝參數能有效控制納米藥物的粒徑，形態，表面性質和穩定性。 / Introduction: In recent years, cocrystallization and nanoprecipitation have gained increasing popularity as viable strategies for improving the pharmaceutical properties and in vivo performance of drugs. The present thesis was aimed at assessing these two approaches for potential applications in pharmaceutical formulation and manufacture with five model drugs, viz. curcumin (CUR), flurbiprofen (FLU), ibuprofen (IBU), ketoprofen (KET) and loxoprofen (LOX). Selection of these drugs for the study was guided mainly by their poor water solubility, poor compactibility, typical drug‘s lipophilicity (log P =3-5), and potential for treatment of Alzheimer‘s disease. Cocrystallization was induced by the attainment of a sufficient supersaturation level through rapid solvent removal from a solution containing the drug and the coformer, nicotinamide (NCT), while flash nanoprecipitation (FNP) was achieved by rapid and homogenous mixing of drug solution (with stabilizer and co-stabilizer if required) with antisolvent in the mixing chamber of a specially designed confined impinging jet mixer (CIJM) or multi-inlet vortex mixer (MIVM). / Methods: Cocrystals were prepared by rotary solvent evaporation or slow evaporation of a solution of drug and NCT in ethanol, and characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, moisture sorption analysis, Fourier transform infrared spectroscopy, intrinsic dissolution rate (IDR) measurement and compaction analysis. Polymer-stabilized drug nanoparticles were prepared by FNP using a two-stream CIJM or four-stream MIVM under defined conditions of varying flowrate, solvent type, molecular weight of amphiphilic diblock (PEG-PLA) copolymer (stabilizer), or drug-to-copolymer ratio. The resulting nanoparticles were characterized for particle size by dynamic light scattering; zeta potential by electrophoretic light scattering; particle morphology and surface properties by scanning electron microscopy and atomic force microscopy; surface composition by X-ray photoelectron spectroscopy (XPS); and drug loading and encapsulation efficiency (EE) by high performance liquid chromatography. / Results: Phase-pure 1:1 cocrystals of IBU and FLU with NCT were obtainable by rotary solvent evaporation, but not slow evaporation. Similar solvent removal failed to cause any cocrystal formation for KET and LOX while inducing partial cocrystal conversion for CUR. Both IBU-NCT and FLU-NCT cocrystals displayed enhanced IDR, reduced moisture sorption and improved tabletability compared with the individual profen crystals. FNP studies using the MIVM confirmed the flowrate, solvent type, molecular weight of PEG-PLA copolymer, and drug-to-copolymer mass ratio being important process variables for controlling particle size and particle stability. Particle stability could be enhanced with a hydrophilic co-stabilizer (e.g., PVA). Such co-stabilizers possibly act by binding to the PEG corona at the particle surface to reinforce the protective steric barrier, as substantiated by XPS data. Comparative studies on nanoparticle production by FNP for the four profens indicated that three structure-related intrinsic solution properties of the profens, namely, water solubility, log P and pKa, were important determinants of the particle size and EE of nanoparticles, as determined by multiple linear regression analysis. / Conclusion: Cocrystallization with NCT can simultaneously improve the tableting behavior, hygroscopicity, and dissolution performance of IBU and FLU. Proper optimization of the process variables in FNP is critical to the controlled production of polymer-stabilized drug nanoparticles with consistent properties and storage stability. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chow, Shing Fung. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 224-247). / Abstracts also in Chinese.