Evaluation of drug physical form during granulation, tabletting and storage

An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated. Despite the spectral similarities between the two drug forms, low levels of API dissociation could be quantified in the tablets; the technique allowed discrimination of around 4% of the API content as the amorphous free base (i.e. less than 1% of the tablet compression weight). API dissociation was shown to be promoted by extended exposure to moisture. Aqueous granulating fluids and manufacturing delays between granulation and drying stages and storage of the tablets in open conditions at 40◦C/75% relative humidity (RH) led to dissociation. In contrast, non-aqueous granulating fluids, with no delay in processing and storage of the tablets in either sealed containers or at lower temperature/humidity prevented detectable dissociation. It is concluded that appropriate manufacturing process and storage conditions for the finished product involved minimising exposure to moisture of the API. Analysis of the drug using FT-Raman spectroscopy allowed rapid optimisation of the process whilst offering quantitative molecular information concerning the dissociation of the drug salt to the amorphous free base form.

Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen

Chitosan and its half-acetylated derivative have been compared as excipients in mucoadhesive tablets containing ibuprofen. Initially the powder formulations containing the polymers and the drug were prepared by either co-spray drying or physical co-grinding. Polymer–drug interactions and the degree of drug crystallinity in these formulations were assessed by infrared spectroscopy and differential scanning calorimetry. Tablets were prepared and their swelling and dissolution properties were studied in media of various pHs. Mucoadhesive properties of ibuprofen-loaded and drug-free tablets were evaluated by analysing their detachment from pig gastric mucosa over a range of pHs. Greater polymer–drug interactions were seen for spray-dried particles compared to co-ground samples and drug loading into chitosan-based microparticles (41%) was greater than the corresponding half-acetylated samples (32%). Swelling and drug release was greater with the half-acetylated chitosan tablets than tablets containing the parent polymer and both tablets were mucoadhesive, the extent of which was dependent on substrate pH. The results illustrate the potential sustained drug delivery benefits of both chitosan and its half-acetylated derivative as mucoadhesive tablet excipients.

Novel polyvinylpyrrolidones to improve delivery of poorly-water soluble drugs; from design to synthesis and evaluation

Polyvinylpyrrolidone is a widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant whereas the cross-linked form is a super-disintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties which have then be polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in most common solvents and in water; properties which suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly-water soluble drug. The results show that the novel PVPs induce the drug to become “X-ray amorphous”, which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks storage.

Interpreting at Vindolanda: commercial and linguistic mediation in the Roman army.

A fragmentary tablet from Vindolanda (Tab. Vindol. II, 213) contains an occurrence of the verb interpretari (‘interpret’, ‘explain’, ‘mediate’) in an apparently commercial context, relating to the grain supply for the Roman fort. This usage is paralleled in a text on a wooden stilus tablet from Frisia in the Netherlands. ‘Interpreters’ and their activities make rather infrequent appearances in the Latin epigraphic and documentary records. In the Danubian provinces, interpreters (interpretes) are attested as army officers and officials in the office of the provincial governor. ‘Interpreters’, in both Latin and Greek inscriptions and papyri, often, however, play more ambiguous roles, not always connected with language-mediation, but also, or instead, with mediation in commercial transactions

Homogeneous and heterogeneous distributed classification for pocket data mining

Pocket Data Mining (PDM) describes the full process of analysing data streams in mobile ad hoc distributed environments. Advances in mobile devices like smart phones and tablet computers have made it possible for a wide range of applications to run in such an environment. In this paper, we propose the adoption of data stream classification techniques for PDM. Evident by a thorough experimental study, it has been proved that running heterogeneous/different, or homogeneous/similar data stream classification techniques over vertically partitioned data (data partitioned according to the feature space) results in comparable performance to batch and centralised learning techniques.

Implementing ‘Site BIM’: a case study of ICT innovation on a large hospital project

Numerous Building Information Modelling (BIM) tools are well established and potentially beneficial in certain uses. However, issues of adoption and implementation persist, particularly for on-site use of BIM tools in the construction phase. We describe an empirical case-study of the implementation of an innovative ‘Site BIM’ system on a major hospital construction project. The main contractor on the project developed BIM-enabled tools to allow site workers using mobile tablet personal computers to access design information and to capture work quality and progress data on-site. Accounts show that ‘Site BIM’, while judged to be successful and actively supporting users, was delivered through an exploratory and emergent development process of informal prototyping. Technical IT skills were adopted into the construction project through personal relationships and arrangements rather than formal processes. Implementation was driven by construction project employees rather than controlled centrally by the corporate IT function.

Therapeutic benefit of low-dose clopidogrel in patients undergoing carotid surgery is linked to variability in the platelet adenosine diphosphate response and patients' weight

BACKGROUND AND PURPOSE: We have previously shown that a single 75-mg tablet of clopidogrel, taken before carotid endarterectomy, significantly reduces postoperative embolization, a marker of thromboembolic stroke. This study explores the antiplatelet effect of this submaximal dose. METHODS: Fifty-six patients on long-term aspirin (150 mg) were randomized to 75 mg clopidogrel or placebo before carotid endarterectomy. Blood samples were taken pre- and postdrug administration and at the end of surgery to measure platelet activation and adenosine diphosphate (ADP) response by flow cytometry and aggregometry. RESULTS: Surgery produced a significant rise in platelet activation in vivo as evidenced by a rise in the percentage of monocyte-platelet aggregates in patients given placebo, but this was not seen in patients receiving clopidogrel. Before surgery, clopidogrel produced a significant reduction in the platelet response to ADP; for example, with 10(-6)M ADP, 77.32+/-2.3% bound fibrinogen in placebo group compared with 67.16+/-3.1% after clopidogrel (P=0.01). This was accentuated after surgery when the percentage of platelets binding fibrinogen in response to ADP was 76.53+/-2.2% in patients given placebo and 62.84+/-3.3% in the clopidogrel group (P=0.002). Similar differences were seen over a range of ADP concentrations and by aggregometry. Platelet responsiveness before treatment was highly variable and was positively correlated with the inhibitory effect of clopidogrel; patients with the highest baseline response to ADP showed the greatest response to clopidogrel. A negative correlation was seen between the effect of clopidogrel and patients' weight (r=0.57; P=0.002). CONCLUSIONS: These results explain how a single 75-mg dose of clopidogrel produces a significant clinical impact on embolization.

Pocket data mining - big data on small devices

Owing to continuous advances in the computational power of handheld devices like smartphones and tablet computers, it has become possible to perform Big Data operations including modern data mining processes onboard these small devices. A decade of research has proved the feasibility of what has been termed as Mobile Data Mining, with a focus on one mobile device running data mining processes. However, it is not before 2010 until the authors of this book initiated the Pocket Data Mining (PDM) project exploiting the seamless communication among handheld devices performing data analysis tasks that were infeasible until recently. PDM is the process of collaboratively extracting knowledge from distributed data streams in a mobile computing environment. This book provides the reader with an in-depth treatment on this emerging area of research. Details of techniques used and thorough experimental studies are given. More importantly and exclusive to this book, the authors provide detailed practical guide on the deployment of PDM in the mobile environment. An important extension to the basic implementation of PDM dealing with concept drift is also reported. In the era of Big Data, potential applications of paramount importance offered by PDM in a variety of domains including security, business and telemedicine are discussed.

iPad use in fieldwork: formal and informal use to enhance pedagogical practice in a bring your own technology world

We report on use of iPads (and other IOS devices) for student fieldwork use and as electronic field notebooks and to promote active. We have used questionnaires and interviews of tutors and students to elicit their views and technology and iPad use for fieldwork. There is some reluctance for academic staff to relinquish paper notebooks for iPad use, whether in the classroom or on fieldwork, as well as use them for observational and measurement purposes. Students too are largely unaware of the potential of iPads for enhancing fieldwork. Apps can be configured for a wide variety of specific uses that make iPads useful for educational as well as social uses. Such abilities should be used to enhance existing practice as well as make new functionality. For example, for disabled students who find it difficult to use conventional note taking. iPads can be used to develop student self-directed learning and for group contributions. The technology becomes part of the students’ personal learning environments as well as at the heart of their knowledge spaces – academic and social. This blurring of boundaries is due to iPads’ usability to cultivate field use, instruction, assessment and feedback processes. iPads can become field microscopes and entries to citizen science and we see the iPad as the main ‘computing’ device for students in the near future. As part of the Bring Your Own Technology/Device (BYOD) the iPad has much to offer although, both staff and students need to be guided in the most effective use for self-directed education via development of Personal Learning Environments. A more student-oriented pedagogy is suggested to correspond to the increasing use of tablet technologies by students

Using mobile devices to enhance undergraduate field research

Mobile devices can enhance undergraduate research projects and students’ research capabilities. The use of mobile devices such as tablet computers will not automatically make undergraduates better researchers, but their use should make investigations, writing, and publishing more effective and may even save students time. We have explored some of the possibilities of using “tablets” and “smartphones” to aid the research and inquiry process in geography and bioscience fieldwork. We provide two case studies as illustration of how students working in small research groups use mobile devices to gather and analyze primary data in field-based inquiry. Since April 2010, Apple’s iPad has changed the way people behave in the digital world and how they access their music, watch videos, or read their email much as the entrepreneurs Steve Jobs and Jonathan Ive intended. Now with “apps” and “the cloud” and the ubiquitous references to them appearing in the press and on TV, academics’ use of tablets is also having an impact on education and research. In our discussion we will refer to use of smartphones such as the iPhone, iPod, and Android devices under the term “tablet”. Android and Microsoft devices may not offer the same facilities as the iPad/iphone, but many app producers now provide versions for several operating systems. Smartphones are becoming more affordable and ubiquitous (Melhuish and Falloon 2010), but a recent study of undergraduate students (Woodcock et al. 2012, 1) found that many students who own smartphones are “largely unaware of their potential to support learning”. Importantly, however, students were found to be “interested in and open to the potential as they become familiar with the possibilities” (Woodcock et al. 2012). Smartphones and iPads could be better utilized than laptops when conducting research in the field because of their portability (Welsh and France 2012). It is imperative for faculty to provide their students with opportunities to discover and employ the potential uses of mobile devices in their learning. However, it is not only the convenience of the iPad or tablet devices or smartphones we wish to promote, but also a way of thinking and behaving digitally. We essentially suggest that making a tablet the center of research increases the connections between related research activities.

Ciprofibrate quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry for pharmacokinetic studies

A rapid, sensitive and specific method for quantifying ciprofibrate in human plasma using bezafibrate as the internal standard (IS) is described. The sample was acidified prior extraction with formic acid (88%). The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (diethyl ether/dichloromethane 70/30 (v/v)). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed using Genesis C18 4 mu m analytical column (4.6 x 150 mm i.d.) and a mobile phase consisting of acetonitrile/water (70/30, v/v) and 1 mM acetic acid. The method had a chromatographic run time of 3.4 min and a linear calibration curve over the range 0.1-60 mu g/mL (r > 0.99). The limit of quantification was 0.1 mu g/mL. The intra- and interday accuracy and precision values of the assay were less than 13.5%. The stability tests indicated no significant degradation. The recovery of ciprofibrate was 81.2%, 73.3% and 76.2% for the 0.3, 5.0 and 48.0 ng/mL standard concentrations, respectively. For ciprofibrate, the optimized parameters of the declustering potential, collision energy and collision exit potential were -51 V, -16 eV and -5 V, respectively. The method was also validated without the use of the internal standard. This HPLC-MS/MS procedure was used to assess the bioequivalence of two ciprofibrate 100 mg tablet formulations in healthy volunteers of both sexes. The following pharmacokinetic parameters were obtained from the ciprofibrate plasma concentration vs. time curves: AUC(last), AUC(0-168 h), C(max) and T(max). The geometric mean with corresponding 90% confidence interval (CI) for test/reference percent ratios were 93.80% (90% CI = 88.16-99.79%) for C(max), 98.31% (90% CI = 94.91-101.83%) for AUC(last) and 97.67% (90% CI = 94.45-101.01%) for AUC(0-168 h). Since the 90% Cl for AUC(last), AUC(0-168 h) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that ciprofibrate (Lipless (R) 100 mg tablet) formulation manufactured by Biolab Sanus Farmaceutica Ltda. is bioequivalent to the Oroxadin (R) (100 mg tablet) formulation for both the rate and the extent of absorption. (C) 2011 Published by Elsevier B.V.

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers

Objective: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (Sao Paulo, Brazil); Reference formulation (1): ibuprofen (Advil (R); 2 x 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (Alivium (R); 8 ml x 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax) AUC(inf) and C-max. Results: The limit of quantification for ibuprofen was 0.1 mu g x ml(-1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C-max, 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUCinf. The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% Cl = 100.195, 117.25%) for C-max, 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 x 200 mg Reference (1) tablets (p < 0.002). Conclusion: Since the 90% CI for AUC(last), AUC(inf) and C-max ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the Advil (R) and Alivium (R) formulations with regard to both the rate and the extent of absorption.

Compatibility studies between captopril and pharmaceutical excipients used in tablets formulations

Captopril (CAP) was the first commercially available angiotensine-converting enzyme (ACE) inhibitor. In the anti-hypertensive therapy is considered the selected drug has to be therapeutically effective together with reduced toxicity. CAP is an antihypertensive drug currently being administered in tablet form. In order to investigate the possible interactions between CAP and excipients in tablets formulations, differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis completed by X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) were used for compatibility studies. A possible drug-excipient interaction was observed with magnesium stearate by DSC technique.

A interatividade na aprendizagem: uma perspectiva cognitiva utilizando conteúdo multimídia

A migração de materiais educacionais para dispositivos portáteis, tais como computadores do tipo tablet, torna possível oferecer altos níveis de interatividade na apresentação de animações e, dessa forma, pesquisas são necessárias para avaliar o valor pedagógico de incorporar recursos sofisticados de interatividade em lições para dispositivos portáteis. Estudantes de Engenharia (no Experimento 1) e estudantes de nível superior de outras áreas (no Experimento 2) estudaram por 5 minutos uma animação mostrando, em um computador do tipo tablet, os seis passos de um procedimento de manutenção para um dispositivo mecânico chamado Tomada de Força. A animação envolveu um baixo nível de interatividade, no qual os estudantes eram capazes de reproduzir, pausar, avançar e voltar a animação por meio de botões acionados em tela sensível ao toque (touch screen); um alto nível de interatividade, no qual os estudantes podiam também tocar e deslizar um dedo na tela para rotacionar a animação ou ainda tocar a tela com dois dedos abrindo-os ou fechando-os para ampliar ou reduzir a animação; ou nenhuma interatividade (apenas no Experimento 2). De forma geral, em ambos os experimentos, os estudantes que utilizaram alto nível de interatividade reportaram maior interesse, mas não mostraram melhor aprendizagem, comparados aos grupos de baixa ou nenhuma interatividade. Entretanto, no Experimento 2, estudantes que se classificaram como alunos verbais demonstraram maior interesse e obtiveram pontuações mais altas de aprendizagem com alta interatividade, em vez de baixa ou nenhuma interatividade. Esse padrão, contudo, não foi encontrado entre os alunos visuais. Também no Experimento 2, os alunos verbais e os alunos com baixo nível de autorregulação de aprendizagem, que manifestaram alto nível de interesse, obtiveram pontuações mais altas de aprendizagem do que os alunos visuais e os alunos com alto nível de autorregulação de aprendizagem, que manifestaram baixo nível de interesse, respectivamente.