Grewia polysaccharide gum as a pharmaceutical excipient

Grewia gum is obtained from the inner stem bark of the edible plant Grewia mollis Juss (Fam. Tiliaceae) which grows widely in the middle belt region of Nigeria, and is also cultivated. The dried and pulverised inner stem bark is used as a thickening agent in some food delicacies in that region of the country. This ability of the material to increase solution viscosity has generated a lot of interest and is the catalysing momentum for this research. Such materials have been used as stabilizers or suspending agents in cosmetics, foods and liquid medications, and as mucoadhesives and controlled release polymeric matrices in solid dosage forms. The physicochemical characterization of candidate excipients forms an essential step towards establishing suitability for pharmaceutical application. For natural gums, this usually requires isolation of the gum from the storage site by extraction processes. Grewia polysaccharide gum was extracted and dried using techniques such as air-drying, freeze-drying or spray-drying. Component analysis of the gum showed that it contains five neutral sugars: glucose, galactose, rhamnose, arabinose and xylose. The gum contains traces of elements such as zinc, magnesium, calcium and phosphorus. At low substance weight, the gum hydrates in aqueous medium swelling and dispersing to give a highly viscous dispersion with pseudoplasmic flow behaviour. The method by which drying is achieved can have significant effect on some physicochemical properties of the gum. Consequently, the intrinsic viscosity and molecular weight, and parameters of powder flow were shown to differ with the method of drying. The gum has good thermal stability. In comparison with established excipients, grewia gum may be preferable to gum Arabic or sodium carboxymethylcellulose as a suspending agent in ibuprofen suspension formulations. The release retardant property of the gum was superior to guar and Metolose® in ibuprofen matrices. Similarly, carboxy methylcellulose, Methocel®, gum Arabic or Metolose® may not be preferable to grewia gum when controlled release of a soluble drug like cimetidine is indicated. The mucoadhesive performance of the gum compared favourably with excellent mucoadhesives such as hydroxypropyl methylcellulose, carboxymethylcellulose, guar and carbopol 971 P.

Novel formulation strategies for the fabrication of lyophilised orally disintegrating tablets

Orally disintegrating Tablets (ODTs), also known as fast-disintegrating, fast-melt or fast-dissolving tablets, are a relatively novel dosage technology that involves the rapid disintegration or dissolution of the dosage form into a solution or suspension in the mouth without the need for water. The solution containing the active ingredients is swallowed, and the active ingredients are then absorbed through the gastrointestinal epithelium to reach the target and produce the desired effect. Formulation of ODTs was originally developed to address swallowing difficulties of conventional solid oral dosage forms (tablets and capsules) experienced by wide range of patient population, especially children and elderly. The current work investigates the formulation and development of ODTs prepared by freeze drying. Initial studies focused on formulation parameters that influence the manufacturing process and performance of lyophilised tablets based on excipients used in commercial products (gelatin and saccharides). The second phase of the work was followed up by comprehensive studies to address the essential need to create saccharide free ODTs using naturally accruing amino acids individually or in combinations. Furthermore, a factorial design study was carried out to investigate the feasibility of delivering multiparticulate systems of challenging drugs using a novel formulation that exploited the electrostatic associative interaction between gelatin and carrageenan. Finally, studies aimed to replace gelatin with ethically and morally accepted components to the end users were performed and the selected binder was used in factorial design studies to investigate and optimise ODT formulations that incorporated drugs with varies physicochemical properties. Our results show that formulation of elegant lyophilised ODTs with instant disintegration and adequate mechanical strength requires carful optimisation of gelatin concentration and bloom strength in addition to saccharide type and concentration. Successful formulation of saccharides free lyophilised ODTs requires amino acids that crystallise in the frozen state or display relatively high Tg', interact and integrate completely with the binder and, also, display short wetting time with the disintegrating medium. The use of an optimised mixture of gelatin, carrageenan and alanine was able to create viscous solutions to suspend multiparticulate systems and at the same time provide tablets with short disintegration times and adequate mechanical properties. On the other hand, gum arabic showed an outstanding potential for use as a binder in the formulation of lyophilised ODTs. Compared to gelatin formulations, the use of gum arabic simplified the formulation stages, shortened the freeze drying cycles and produced tablets with superior performance in terms of the disintegration time and mechanical strength. Furthermore, formulation of lyophilised ODTs based on gum arabic showed capability to deliver diverse range of drugs with advantages over commercial products.

The Single drop drying of heat-sensitive materials

The literature relating to the principles and practice of drying of materials, particularly those susceptible to thermal degradation or undesirable loss of volatile components, has been reviewed. Single droplets of heat-sensitive materials were dried whilst suspended in a horizontal wind tunnel from a specially-designed, rotating thermocouple which enabled direct observation of drying behaviour and continuous measurement of droplet temperature as drying progressed. The effects of drying air temperature and initial solids concentration on the potency of various antibiotics, viz. ampicillin, chloramphenicol, oxytetracycline, streptomycin and tetracycline, were assessed using a modified Drug Sensitivity Testing technique. Only ampicillin was heat-sensitive at temperatures above 100°C, e.g. at an air temperature of 115°C its zone diameter was reduced from 100% to 45%. Selected enzymes, viz. dextran sucrase and invertase, were also dried and their residual activities determined by High Performance Liquid Chromatography. The residual activity of dextran sucrase was rapidly reduced at temperatures above 65°C, and the residual activity of invertase reduced rapidly at temperatures above 65°C; but drying with short residence times will retain most of its activity. The performance of various skin-forming encapsulants, viz. rice and wheat starch, dextrin, coffee, skim milk, fructose, gelatine 60 and 150 Bloom, and gum arabic, was evaluated to determine their capabilities for retention of ethanol as a model volatile, under different operating conditions. The effects of initial solids concentration, air velocity and temperature were monitored for each material tested. Ethanol content was analysed by Gas Liquid Chromatography and in some cases dried crusts were removed for examination. Volatiles retention was concluded to depend in all cases upon the rate and nature of the skin formation and selective diffusion phenomena. The results provided further insight into the inter-relationship between temperature, residence time and thermal degradation of heat-sensitive materials. They should also assist in selection of the preferred dryer for such materials, and of the operating parameter to enable maximum retention of the required physico-chemical characteristics in the dried materials.

Relating two simultaneous events in discourse: the role of on-goingness devices in L1 Tunisian Arabic, L1 French and L2 French by Tunisian learners

Our PhD study focuses on the role of aspectual marking in expressing simultaneity of events in Tunisian Arabic as a first language, French as a first language, as well as in French as a second language by Tunisian learners at different acquisitional stages. We examine how the explicit markers of on-goingness qa:’id and «en train de» in Tunisian Arabic and in French respectively are used to express this temporal relation, in competition with the simple forms, the prefixed verb form in Tunisian Arabic and the présent de l’indicatif in French. We use a complex verbal task of retelling simultaneous events sharing an interval on the time axis based on eight videos presenting two situations happening in parallel. Two types of simultaneity are exploited: perfect simultaneity (when the two situations are parallel to each other) and inclusion (one situation is framed by the second one). Our informants in French and in Tunisian Arabic have two profiles, highly educated and low educated speakers. We show that the participants’ response to the retelling task varies according to their profiles, and so does their use of the on-goingness devices in the expression of simultaneity. The differences observed between the two profile groups are explained by the degree to which the speakers have developed a habit of responding to tasks. This is a skill typically acquired during schooling. We notice overall that the use of qa:’id as well as of «en train de» is less frequent in the data than the use of the simple forms. However, qa:’id as well as «en train de» are employed to play discursive roles that go beyond the proposition level. We postulate that despite the shared features between Tunisian Arabic and French regarding marking the concept of on-goingness, namely the presence of explicit lexical, not fully grammaticalised markers competing with other non-marked forms, the way they are used in the discourse of simultaneous events shows clear differences. We explain that «en train de» plays a more contrastive role than qa:’id and its use in discourse obeys a stricter rule. In cases of the inclusion type of simultaneity, it is used to construe the ‘framing’ event that encloses the second event. In construing perfectly simultaneneous events, and when both «en train de» and présent de l’indicatif are used, the proposition with «en train de» generally precedes the proposition with présent de l’indicatif, and not the other way around. qa:id obeys, but to a less strict rule as it can be used interchangeably with the simple form regardless of the order of propositions. The contrastive analysis of French L1 and L2 reveals learners’ deviations from natives’ use of on-goingness devices. They generalise the use of «en train de» and apply different rules to the interaction of the different marked and unmarked forms in discourse. Learners do not master its role in discourse even at advanced stages of acquisition despite its possible emergence around the basic and intermediate varieties. We conclude that the native speakers’ use of «en train de» involves mastering its role at the macro-structure level. This feature, not explicitly available to learners in the input, might persistently present a challenge to L2 acquisition of the periphrasis.

Computer-aided categorisation and quantification of connectives in English and Arabic (based on newspaper text corpora).

This study presents a detailed contrastive description of the textual functioning of connectives in English and Arabic. Particular emphasis is placed on the organisational force of connectives and their role in sustaining cohesion. The description is intended as a contribution for a better understanding of the variations in the dominant tendencies for text organisation in each language. The findings are expected to be utilised for pedagogical purposes, particularly in improving EFL teaching of writing at the undergraduate level. The study is based on an empirical investigation of the phenomenon of connectivity and, for optimal efficiency, employs computer-aided procedures, particularly those adopted in corpus linguistics, for investigatory purposes. One important methodological requirement is the establishment of two comparable and statistically adequate corpora, also the design of software and the use of existing packages and to achieve the basic analysis. Each corpus comprises ca 250,000 words of newspaper material sampled in accordance to a specific set of criteria and assembled in machine readable form prior to the computer-assisted analysis. A suite of programmes have been written in SPITBOL to accomplish a variety of analytical tasks, and in particular to perform a battery of measurements intended to quantify the textual functioning of connectives in each corpus. Concordances and some word lists are produced by using OCP. Results of these researches confirm the existence of fundamental differences in text organisation in Arabic in comparison to English. This manifests itself in the way textual operations of grouping and sequencing are performed and in the intensity of the textual role of connectives in imposing linearity and continuity and in maintaining overall stability. Furthermore, computation of connective functionality and range of operationality has identified fundamental differences in the way favourable choices for text organisation are made and implemented.

Cohesion in text differentiation : a study of English and Arabic

This thesis sets out to investigate the role of cohesion in the organisation and processing of three text types in English and Arabic. In other words, it attempts to shed some light on the descriptive and explanatory power of cohesion in different text typologies. To this effect, three text types, namely, literary fictional narrative, newspaper editorial and science were analysed to ascertain the intra- and inter-sentential trends in textual cohesion characteristic of each text type in each language. In addition, two small scale experiments which aimed at exploring the facilitatory effect of one cohesive device (i.e. lexical repetition) on the comprehension of three English text types by Arab learners were carried out. The first experiment examined this effect in an English science text; the second covered three English text types, i.e. fictional narrative, culturally-oriented and science. Some interesting and significant results have emerged from the textual analysis and the pilot studies. Most importantly, each text type tends to utilize the cohesive trends that are compatible with its readership, reader knowledge, reading style and pedagogical purpose. Whereas fictional narratives largely cohere through pronominal co-reference, editorials and science texts derive much cohesion from lexical repetition. As for cross-language differences English opts for economy in the use of cohesive devices, while Arabic largely coheres through the redundant effect created by the high frequency of most of those devices. Thus, cohesion is proved to be a variable rather than a homogeneous phenomenon which is dictated by text type among other factors. The results of the experiments suggest that lexical repetition does facilitate the comprehension of English texts by Arab learners. Fictional narratives are found to be easier to process and understand than expository texts. Consequently, cohesion can assist in the processing of text as it can in its creation.

Organizational and textual structuring of radio news discourse in English and Arabic.

The present work studies the overall structuring of radio news discourse via investigating three metatextual/interactive functions: (1) Discourse Organizing Elements (DOEs), (2) Attribution and (3) Sentential and Nominal Background Information (SBI & NBI). An extended corpus of about 73,000 words from BBC and Radio Damascus news is used to study DOEs and a restricted corpus of 38,000 words for Attribution and S & NBI. A situational approach is adopted to assess the influence of factors such as medium and audience on these functions and their frequence. It is found that: (1) DOEs are organizational and their frequency is determined by length of text; (2) Attribution Function in accordance with the editor's strategy and its frequency is audience sensitive; and (3) BI provides background information and is determined by audience and news topics. Secondly, the salient grammatical elements in DOEs are discourse deictic demonstratives, address pronouns and nouns referring to `the news'. Attribution is realized in reporting/reported clauses, and BI in a sentence, a clause or a nominal group. Thirdly, DOEs establish a hierarchy of (1) news, (2) summary/expansion and (3) item: including topic introduction and details. While Attribution is generally, and SBI solely, a function of detailing, NBI and proper names are generally a function of summary and topic introduction. Being primarily addressed to audience and referring metatextually, the functions investigated support Sinclair's interactive and autonomous planes of discourse. They also shed light on the part(s) of the linguistic system which realize the metatextual/interactive function. Strictly, `discourse structure' inevitably involves a rank-scale; but news discourse also shows a convention of item `listing'. Hence only within the boundary of variety (ultimately interpreted across language and in its situation) can textual functions and discourse structure be studied. Finally, interlingual variety study provides invaluable insights into a level of translation that goes beyond matching grammatical systems or situational factors, an interpretive level which has to be described in linguistic analysis of translation data.

The release of nicotine from chewing gum formulations

The first clinically proven nicotine replacement product to obtain regulatory approval was Nicorette® gum. It provides a convenient way of delivering nicotine directly to the buccal cavity, thus, circumventing 'first-pass' elimination following gastrointestinal absorption. Since launch, Nicorette® gum has been investigated in numerous studies (clinical) which are often difficult to compare due to large variations in study design and degree of sophistication. In order to standardise testing, in 2000 the European Pharmacopoeia introduced an apparatus to investigate the in vitro release of drug substances from medical chewing gum. With use of the chewing machine, the main aims of this project were to determine factors that could affect release from Nicorette® gum, to develop an in vitro in vivo correlation and to investigate formulation variables on release of nicotine from gums. A standard in vitro test method was developed. The gum was placed in the chewing chamber with 40 mL of artificial saliva at 37'C and chewed at 60 chews per minute. The chew rate, the type of dissolution medium used, pH, volume, temperature and the ionic strength of the dissolution medium were altered to investigate the effects on release in vitro. It was found that increasing the temperature of the dissolution media and the rate at which the gums were chewed resulted in a greater release of nicotine, whilst increasing the ionic strength of the dissolution medium to 80 mM resulted in a lower release. The addition of 0.1 % sodium Jauryl sulphate to the artificial saliva was found to double the release of nicotine compared to the use of artificial saliva and water alone. Although altering the dissolution volume and the starting pH did not affect the release. The increase in pH may be insufficient to provide optimal conditions for nicotine absorption (since the rate at which nicotine is transported through the buccal membrane was found to be higher at pH values greater than 8.6 where nicotine is predominately unionised). Using a time mapping function, it was also possible to establish a level A in vitro in vivo correlation. 4 mg Nicorette® gum was chewed at various chew rates in vitro and correlated to an in vivo chew-out study. All chew rates used in vitro could be successfully used for IVIVC purposes, however statistically, chew rates of 10 and 20 chews per minute performed better than all other chew rates. Finally a series of nicotine gums was made to investigate the effect of formulation variables on release of nicotine from the gum. Using a directly compressible gum base, in comparison to Nicorette® the gums crumbled when chewed in vitro, resulting in a faster release of nicotine. To investigate the effect of altering the gum base, the concentration of sodium salts, sugar syrup, the form of the active drug, the addition sequence and the incorporation of surfactant into the gum, the traditional manufacturing method was used to make a series of gum formulations. Results showed that the time of addition of the active drug, the incorporation of surfactants and using different gum base all increased the release of nicotine from the gum. In contrast, reducing the concentration of sodium carbonate resulted in a lower release. Using a stronger nicotine ion-exchange resin delayed the release of nicotine from the gum, whilst altering the concentration of sugar syrup had little effect on the release but altered the texture of the gum.

Metaphor in (Arabic-into-English) translation with specific reference to metaphorical concepts and expressions in political discourse

Cognitive linguistics scholars argue that metaphor is fundamentally a conceptual process of mapping one domain of experience onto another domain. The study of metaphor in the context of Translation Studies has not, unfortunately, kept pace with the discoveries about the nature and role of metaphor in the cognitive sciences. This study aims primarily to fill part of this gap of knowledge. Specifically, the thesis is an attempt to explore some implications of the conceptual theory of metaphor for translation. Because the study of metaphor in translation is also based on views about the nature of translation, the thesis first presents a general overview of the discipline of Translation Studies, describing the major models of translation. The study (in Chapter Two) then discusses the major traditional theories of metaphor (comparison, substitution and interaction theories) and shows how the ideas of those theories were adopted in specific translation studies of metaphor. After that, the study presents a detailed account of the conceptual theory of metaphor and some hypothetical implications for the study of metaphor in translation from the perspective of cognitive linguistics. The data and methodology are presented in Chapter Four. A novel classification of conceptual metaphor is presented which distinguishes between different source domains of conceptual metaphors: physical, human-life and intertextual. It is suggested that each source domain places different demands on translators. The major sources of the data for this study are (1) the translations done by the Foreign Broadcasting Information Service (FBIS), which is a translation service of the Central Intelligence Agency (CIA) in the United Sates of America, of a number of speeches by the Iraqi president Saddam Hussein during the Gulf Crisis (1990-1991) and (2) official (governmental) Omani translations of National Day speeches of Sultan Qaboos bin Said of Oman.

An initial evaluation of gellan gum as a material for tissue engineering applications

Alpha-modified minimum essential medium (αMEM) has been found to cross-link a 1% gellan gum solution, resulting in the formation of a self-supporting hydrogel in 1:1 and 5:1 ratios of polysaccharide: αMEM. Rheological data from temperature sweeps confirm that in addition to orders of magnitude differences in G' between 1% gellan and 1% gellan with αMEM, there is also a 20°C increase in the temperature at which the onset of gelation takes place when αMEM is present. Frequency sweeps confirm the formation of a true gel; mechanical spectra for mixtures of gellan and αMEM clearly demonstrate G' to be independent of frequency. It is possible to immobilize cells within a three-dimensional (3D) gellan matrix that remain viable for up to 21 days in culture by adding a suspension of rat bone marrow cells (rBMC) in αMEM to 1% gellan solution. This extremely simple approach to cell immobilization within 3D constructs, made possible by the fact that gellan solutions cross-link in the presence of millimolar concentrations of cations, poses a very low risk to a cell population immobilized within a gellan matrix and thus indicates the potential of gellan for use as a tissue engineering scaffold. © 2007 Sage Publications.

Verbal negation in the inter-language of Arabic-speaking women acquiring English as a second language

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Translation and peace:Arabic, English and Hebrew versions of Israeli-Palestinian peace initiatives

The present thesis examines Palestinian-Israeli peace initiatives as politically negotiated texts and their different Arabic, English and Hebrew language versions. Its aim is to make a contribution to a deeper understanding of the role of translation and recontextualization of politically negotiated texts in situations of ongoing contemporary conflict. In modern Translation Studies, although research exists on the translation of political texts following functional (e.g. Schäffner 2002) or systemic-linguistic (e.g. Calzada-Pérez 2001) approaches or applying narrative theory (Baker 2006), peace initiatives and politically negotiated texts are still a largely under-researched genre of political texts. The thesis – which takes 31 Arabic, English and Hebrew language versions of 5 different Palestinian-Israeli peace initiatives as its corpus – operates within the framework of product-oriented Descriptive Translation Studies (Lambert and Van Gorp 1985) and Critical Discourse Analysis (Fairclough 1992). For all of the peace initiatives analysed, there exist several language versions which were made available in different contexts by different institutions and for different readerships and purposes. The thesis pursues a top-down approach. It begins with presenting the socio-cultural and political contexts of the production of the original versions of the respective peace initiatives (the source texts) and their different language versions (target texts), focusing on their underlying functions and principles of audience design. It then moves to examine how the textual profiles of the language versions of peace initiatives reflect aspects of ideology, political affiliation and power relations at both the macro- and micro-structural levels. The final step is to account for these aspects in terms of socio-political and institutional conditions of the production of the translations. The overall textual analysis demonstrates that when translated, peace initiatives can be interpreted differently by different institutions in their attempt to promote their respective political interests and narratives. Also, it is very frequently that translations produced in one specific institutional context are recontextualised for use in another one. Such recontextualisation goes hand in hand with further textual amendments. To summarize, the thesis demonstrates how these translations – as products – are (re)framed and (re)contextualized in different institutional settings in order to serve different purposes. These texts, thus, play different roles in situations of ongoing contemporary conflict depending on the institutional context in which they are presented and the purposes they set to serve. These main findings make an original contribution to the discipline of Translation Studies in respect of emphasizing the need to study translations in their socio-political, historical and institutional contexts.

Preformulation studies on grewia gum as a formulation excipient

Grewia gum is a naturally occurring polysaccharide which has potential as a pharmaceutical excipient. Differential scanning calorimetry and Fourier transform infrared (FT-IR) spectroscopy techniques were used to examine the thermal and molecular behaviours, respectively, of mixtures of grewia gum with cimetidine, ibuprofen or standard excipients, to assess potential interactions. No disappearance or broadening of the melting endotherm was seen with cimetidine or ibuprofen. Similarly, there was no interaction between grewia gum and the standard excipients tested. The results obtained using thermal analyses were supported by FT-IR analysis of the material mixtures. Grewia gum is an inert natural polymer which can be used alone or in combination with other excipients in the formulation of pharmaceutical dosage forms. © 2011 Akadémiai Kiadó, Budapest, Hungary.