Preliminary Formulations Research Articles

APPLICATION OF 32 CENTRAL COMPOSITE DESIGN FOR THE FORMULATION OF RAPID SOLUBLE ORODISPERSIBLE FILM OF DIPYRIDAMOLE

Objective: The aim of this investigation is to formulate, design, optimize and to an evaluation of the rapid soluble orodispersible film (OTF) of dipyridamole (DPI) using the solvent casting method by 32 central composite designs. Methods: Statistical design was used to optimize the preliminary formulations by selecting independent variables such as a polymer (HPMC-E52V, X1) and plasticizer (PEG400, X2) concentration as film-forming polymer and as a plasticizer and the dependent variables such as the release of drug in percentage (Y1), time of disintegration (sec, Y2) and tensile strength (N/m2 Y3). Results: The content of the drug was resulted in the range of 95.05–101 %. The physical properties were found to be colorless and homogenously clear and smooth surface. The folding endurance shown as without any scratches with the pH ranges from 6.35 to 6.75 and the prepared film was not irritated to the oral mucosa. Conclusion: The prepared films showed an optimum time of disintegration that is 25 sec, 96.74% drug release in phosphate buffer of pH 6.8 at initial 5 min and 85.98 % ex-vivo permeation studies after 30 min.

Estudo preliminar da síntese de geopolímeros baseados em metacaulim, cinzas volantes e filito da Região Sudeste do Pará

Este trabalho apresenta um estudo preliminar da síntese de geopolímeros com matérias primas e coprodutos provenientes da região Sul e Sudeste do Pará, no qual foram definidas 4 formulações para avaliação da resistência mecânica através de ensaios de resistência à compressão. Os insumos inicialmente escolhidos foram: metacaulim, filito, cinza volante e escória de aciaria; estes dois últimos sendo coprodutos industriais. Na confecção das formulações preliminares foi utilizado como ativador alcalino a solução de NaOH 12M, bem como o silicato de sódio (Na2SiO3) como solução aditivadora. Entre as amostras ensaiadas, duas formulações obtiveram resistência à compressão da ordem de 20,5 e 21 MPa, com respectivamente 15 e 28 dias de cura, com adição do silicato de sódio.

Design and Characterization of Mucoadhesive Microspheres of Etodolac

Mucoadhesive microspheres are drug delivery system intended for drug targeting to a specific region. Etodolac is a Non-steroidal anti-inflammatory drug. Sustain released Etodolac loaded mucoadhesive microspheres were prepared to overcome the relatively short residence time of Etodolac in the GIT tract before elimination. Solvent evaporation method was used for preparation of mucoadhesive microspheres with the help of Carbopol 974P, HPMC K100M and HPMC K4M as the polymers. Central composite design was selected for the development of the formulation. The formulations were evaluated for their particle size, surface morphology, degree of swelling, entrapment efficiency, drug content and in-vitro drug release study was done. Based on the results obtained from the preliminary formulations three optimized formulations were designed. The percentage mucoadhesion and swelling index of these formulations were obtained in the range of 66-70% and 82.50-83.84% respectively. Optimized formulation releases 90.94% to 92.11% of drug after 10 hours and follows zero order kinetics.

A Computational Model of Immanent Accent Salience in Tonal Music.

Accents are local musical events that attract the attention of the listener, and can be either immanent (evident from the score) or performed (added by the performer). Immanent accents involve temporal grouping (phrasing), meter, melody, and harmony; performed accents involve changes in timing, dynamics, articulation, and timbre. In the past, grouping, metrical and melodic accents were investigated in the context of expressive music performance. We present a novel computational model of immanent accent salience in tonal music that automatically predicts the positions and saliences of metrical, melodic and harmonic accents. The model extends previous research by improving on preliminary formulations of metrical and melodic accents and introducing a new model for harmonic accents that combines harmonic dissonance and harmonic surprise. In an analysis-by-synthesis approach, model predictions were compared with data from two experiments, respectively involving 239 sonorities and 638 sonorities, and 16 musicians and 5 experts in music theory. Average pair-wise correlations between raters were lower for metrical (0.27) and melodic accents (0.37) than for harmonic accents (0.49). In both experiments, when combining all the raters into a single measure expressing their consensus, correlations between ratings and model predictions ranged from 0.43 to 0.62. When different accent categories of accents were combined together, correlations were higher than for separate categories (r = 0.66). This suggests that raters might use strategies different from individual metrical, melodic or harmonic accent models to mark the musical events.

An Application of Peircean Triadic Logic: Modelling Vagueness

Development of decision-support and intelligent agent systems necessitates mathematical descriptions of uncertainty and fuzziness in order to model vagueness. This paper seeks to present an outline of Peirce’s triadic logic as a practical new way to model vagueness in the context of artificial intelligence (AI). Charles Sanders Peirce (1839–1914) was an American scientist–philosopher and a great logician whose triadic logic is a culmination of the study of semiotics and the mathematical study of anti-Cantorean model of continuity and infinitesimals. After presenting Peircean semiotics within AI perspective, a mathematical formulation of a Peircean triadic set is given in relationship with classical and fuzzy sets. Using basic logical operators, all possible respective implication operators, bi-equivalence operators, valid rules of inference, and associative, distributive and commutative logical properties are derived and verified through the truth function approach. In order to suggest practical directions, aggregation operators for Peirce’s triadic logic have been formulated. A mathematical formulation of a medical diagnostic problem and ER diagram of a library management system using Peirce’s triadic relation show potential for further applications of the proposed triadic set and triadic logic. Alongside, a classical AI game—The Wumpus World—is implemented to show practical efficacy in comparison with binary implementation. Besides giving some preliminary formulations for trichotomous set theory and definition of finite automaton, development of hybrid architectures for intelligent agents and evolutionary computations are discussed as potential practical avenues for Peirce’s triadic logic.

Pharmacological Treatment of Schizophrenia in Light of Phenomenology

The contribution of phenomenology to the field of psychopathology should be treated as a living legacy. The singularities of the method, which have promoted the humanistic and deep understanding of mental suffering for over a century, still leave much to be explored by psychiatry especially within the therapeutic context. The phenomenological validity of the different meanings of treatment of mental disorders is one of the great challenges of our times. Within the domain of this vast research project, some preliminary formulations in the field of schizophrenia will be presented. Initially, a brief contextualization of the developments of phenomenological psychopathology as a whole will be made. Next, the legitimacy of the phenomenological investigation of pharmacological treatment will be defended as will be defended the pressing need for such investigation. Finally, based on anthropological principles, one essential property of antipsychotics in the constitutive disturbance of schizophrenia are proposed. Some direct implications in the clinical setting of this qualitative assessment of the pharmacological treatment of schizophrenia are also identified.

Efficacy of a Magnolia officinalis bark extract against grapevine downy mildew and apple scab under controlled and field conditions

In organic agriculture, the control of several diseases is largely depending on copper fungicides. Yet, copper can accumulate in the soil if the annual input exceeds annual uptake by plants, which can have a negative impact on soil fertility. Its use should thus be avoided or reduced. The aim of the present study was to evaluate the efficacy of a bark extract of Magnolia officinalis Rehder and Wilson to control three pathogens including Plasmopara viticola (Berk. & M.A. Curtis) Berl. & De Toni (causing grapevine downy mildew), Venturia inaequalis (Cooke) G. Winter (causing apple scab), and Phytophthora infestans (Mont.) De Bary (causing potato and tomato late blight) under controlled and field conditions, and to identify compounds responsible for the antifungal activity of the extract. Under controlled conditions, M. officinalis bark extract showed a mean efficacy of 97% (P. viticola) and 93% (V. inaequalis) at 1 mg mL−1, and EC50 between 0.14 and 0.20 mg mL−1. Efficacy against P. infestans was comparatively low (52% at 1 mg mL−1). Magnolol and honokiol were identified as the main active compounds, both with EC50 ≤ 0.08 mg mL−1 against P. viticola and V. inaequalis. Under field conditions, preliminary formulations reached efficacies up to 71% at 1–2 mg plant extract mL−1 against grapevine downy mildew, whereas activity against apple scab could not be confirmed. Magnolia officinalis is a promising candidate for the development of a sustainable plant protection product against grapevine downy mildew due to a combination of good efficacy, high availability of the raw material at affordable prices, reasonable extraction efficiency, and expected low human toxicity due to its longstanding use in traditional Chinese medicine.

Nanoencapsulation of Thymus capitatus essential oil: Formulation process, physical stability characterization and antibacterial efficiency monitoring

This work aimed to nanoencapsulate Thymus capitatus essential oil as natural food preservative. To fix ingredients type and concentrations, preliminary formulations were tested for their droplet size average and distribution. Emulsions stability was investigated for 12 days and the antibacterial activity of bulk and encapsulated essential oil were studied. Results showed that nanoemulsions containing 1% of SDS as emulsifier and 10% of dispersed phase containing 70% of the essential oil have an appropriate droplet diameter averages (around 110 nm). Stability tests demonstrated that nanoemulsions, stored at 4 °C, showed the highest stability. Moreover, antibacterial activity results exhibited the improvement of encapsulated T. capitatus essential oil efficiencies as compared to bulk one. In fact, nanoemulsion presented higher bacterial growth inhibition, lower minimum inhibitory and bactericidal concentrations, and better time kinetic results, as compared to bulk one. Gathered results provide useful information for designing effective natural preservatives that inhibit food bacterial spoilage.

Comparação entre os conceitos de self na FAP, na ACT e na obra de Skinner

Diversos autores da Análise do Comportamento debatem sobre o conceito de self, incluindo B. F. Skinner, os proponentes da Psicoterapia Analítica Funcional (FAP) e da Terapia de Aceitação e Compromisso (ACT). Entretanto, apesar da relevância dessas duas modalidades terapêuticas, as discussões a respeito do self têm carecido de uma integração entre as propostas. O presente artigo tem como objetivo fazer um breve levantamento sobre a noção de self na obra de Skinner e nos escritos da FAP e da ACT, apontando diferenças e semelhanças. Para isso, foi apresentado o processo de construção do conceito de self desde as formulações preliminares a respeito do Eu na obra Skinneriana, passando pelos textos da FAP e da ACT. A partir dessas definições, foram descritos padrões de interação entre o indivíduo e o ambiente em termos de relações funcionais e princípios comportamentais, culminando em três categorias diagnósticas funcionais que exemplificam os problemas psicológicos mais relatados nos consultórios.

Organizing principles as tools for bridging the gap between system theory and biological experimentation.

Twentieth-century theoretical efforts towards the articulation of general system properties came short of having the significant impact on biological practice that their proponents envisioned. Although the latter did arrive at preliminary mathematical formulations of such properties, they had little success in showing how these could be productively incorporated into the research agenda of biologists. Consequently, the gap that kept system-theoretic principles cut-off from biological experimentation persisted. More recently, however, simple theoretical tools have proved readily applicable within the context of systems biology. In particular, examples reviewed in this paper suggest that rigorous mathematical expressions of design principles, imported primarily from engineering, could produce experimentally confirmable predictions of the regulatory properties of small biological networks. But this is not enough for contemporary systems biologists who adopt the holistic aspirations of early systemologists, seeking high-level organizing principles that could provide insights into problems of biological complexity at the whole-system level. While the presented evidence is not conclusive about whether this strategy could lead to the realization of the lofty goal of a comprehensive explanatory integration, it suggests that the ongoing quest for organizing principles is pragmatically advantageous for systems biologists. The formalisms postulated in the course of this process can serve as bridges between system-theoretic concepts and the results of molecular experimentation: they constitute theoretical tools for generalizing molecular data, thus producing increasingly accurate explanations of system-wide phenomena.

Synthesis and biodegradation of di-vinyl monomers containing different antimicrobial agents for use in dental adhesive systems

Event Abstract Back to Event Synthesis and biodegradation of di-vinyl monomers containing different antimicrobial agents for use in dental adhesive systems Yasaman Delaviz1* and J Paul Santerre1, 2* 1 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada 2 University of Toronto, Faculty of Dentistry, Canada Introduction: More than 50% of dental restorations placed annually are resin composites[1]. However, these materials experience significant biological breakdown in the oral cavity that is believed to be facilitated by oral bacteria which migrate within the margin between the tooth and restorative material. Ciprofloxacin (CF) and Metronidazole (MN) are two antimicrobial agents with potential to manage oral bacterial in the margin environment[2],[3] Previous work reported on the synthesis of CF derived vinyl monomers for adhesives [4]. The objectives of the current work are to synthesize an antimicrobial di-vinyl monomer that will release MN upon hydrolytic degradation, and to formulate adhesive systems containing a combination of both MN and CF derived di-vinyl monomers. Methods: A lysine/hydroxyl-methyl methacrylate (HLH) derivative was synthesized [5]. Using carbodiimide chemistry, the hydroxyl moiety of MN was coupled to HLH acidified ester, yielding HLH-MN. The monomer was characterized by nuclear magnetic resonance. Biodegradation studies (0.1mM) of HLH, HLH-MN and commercial Bisphenol A-glycidyl methacrylate (BisGMA) (n=9, repeated 3 times) were carried out at 37⁰C in buffer or enzyme solution (containing cholesterol esterase activity and pseudocholinesterase activity) for 4 days and solutions characterized by high performance liquid chromatography (HPLC)[5],[6]. Preliminary formulations of CF and MN derived monomers were light cured (1min) using camphorquinone/2-(dimethyl-amino) ethyl methacrylate photo-initiator system, with commercial monomers BisGMA and 2-hydroxyethyl methacrylate (HEMA)[4]. Gel contents were determined and cell toxicity compared using human gingival fibroblasts. Results and Discussion: HLH-MN structure was confirmed by 1H-NMR (Fig 1). The amount of MN released was not significantly different between the buffer or enzyme condition (Fig 2a), whereas it was for BisGMA[7]. HLH-MN was more stable than BisGMA under enzymatic conditions (Fig 2b). The rate of MN released in buffer (4.091 µM/day, r2 = 0.99) was much greater than CF (0.039 µM/day, r2 = 0.86). The linkage between the backbone and MN is an ester while CF is coupled via a more stable amide. This will play to the advantage of each of the drugs relative to minimum inhibitory concentrations (MICs) for Streptococcus mutans, (0.7 µg/mL for CF vs 700 µg/mL for MN). The gel content for cured adhesives with weight percent values for MN:CF:Hema:BisGMA of 5:10:30:55; 10:5:30:55, and 15:15:15:55 were 99.2% (±0.5), 99.0% (±0.7) and 96.0% (±2.8), respectively. These high conversion states are anticipated to yield good cell compatibility in on-going work. Figure 1. 1H-NMR(CDCl3, 400MHz) of HLH-MN, the drug MN is highlighted in blue. Figure 2. Degradation (a) by-products MN and BisHPPP released and (b) remaining monomer in solution, under buffer (DPBS) or enzyme conditions. Conclusion: HLH-MN, which polymerizes with a high degree of cross-linking, is more hydrolytically stable in comparison to BisGMA and releases MN upon degradation. On-going work is assessing the efficacy of the drug release for the combination systems and determining an optimal formulation of the two drug monomer adhesive system with respect to mechanical, chemical and biological stability. The authors would like to thank Dr. Meilin Yang for his scientific input and expertise in chemistry; NSERC CGS and NSERC Discovery Grant #360520

Mucoadhesive polymers-based film as a carrier system for sublingual delivery of glutathione.

The sublingual mucosa provides a promising route for the delivery of glutathione (GSH). However, challenges are encountered in developing sublingual mucoadhesive drug delivery formulations such as: prolonging drug retention, uniform drug content, desirable drug release profiles, adequate drug permeation and efficient delivery of GSH. The aim of this study was to develop a suitable mucoadhesive polymer-based sublingual film. The mucoadhesive films were prepared by casting method. Several characterization studies including thickness, weight uniformity, surface pH, elongation, mucoadhesiveness, swelling and erosion were carried out on preliminary formulations to optimise formulations for in-vitro drug release and ex-vivo permeation studies. The optimal mucoadhesive polymer-based films showed acceptable physical properties and good mucoadhesion, and remained attached to excised porcine sublingual mucosa for sufficient time, providing a sustained delivery of GSH through the mucosal epithelial. The optimal mucoadhesive films may provide a promising drug delivery platform to develop commercial sublingual products of GSH as well as a wide range of protein and peptide drugs.

Sex is Blind: Some Preliminary Theoretical Formulations

Is the gender disparity in sexual experience the same for men and women who are blind? Perhaps being impervious to visual cues would generate restrained sexual appetites in both genders. Our ethnographic findings suggest otherwise; the gender disparity persists even among men and women who are blind. The findings are discussed in terms of the cross-species research on multiple cues underlying mate selection, the combined utility of mate selection traits, and the physiological significance of sexual pleasure. Brief excerpts from our interviews are also included.

Design and Characterization of Sustained Release Mucoadhesive Microspheres of Tolterodine Tartrate

The work was aim to design and characterize the sustained release mucoadhesive microspheres of Tolterodine tartrate prepared by non-aqueous solvent evaporation technique using ethyl cellulose based selected mucoadhesive polymers. Selected microspheres formulations of were found to be discrete, spherical and free flowing from the preliminary formulations. The microspheres exhibit good mucoadhesive property in in-vitro wash off test and showed high drug entrapment efficiency. Tolterodine tartrate release from these microspheres was slowed, extended and depended on the concentration of ethyl cellulose and type of mucoadhesive polymer used. In vitro drug release studies suggested that formulation F6c showed consistent drug release for up to 24 h time period. Among all the formulations, F6c containing ethyl cellulose with chitosan showed the reproducible results with best mucoadhesive profile and good surface morphology. The correlation value (r(2)) indicated that the drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all formulations at P < 0.05 level. Accelerated stability study of optimized formulation (F6c) up to 3 month showed there was no change in drug content and release characteristics during storage.

Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties

Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole

Consistent Parameterization of Roughness Length and Displacement Height for Sparse and Dense Canopies in Land Models

Abstract While progress has been made in the treatment of turbulence below, within, and above canopy in land models, not much attention has been paid to the convergence of canopy roughness length and displacement height to bare soil values as the above-ground biomass, or the sum of leaf and stem area indices, becomes zero. Preliminary formulations have been developed to ensure this convergence for the Community Land Model version 3 (CLM3) and are found to significantly improve the wintertime simulation of sensible heat flux (SH) compared with observational data over the Cabauw site in the Netherlands. The simulation of latent heat flux (LH) is also moderately improved. For global offline CLM3 simulations, the new formulations change SH by more than 5 W m−2 over many regions, while the change of LH is less than 1 W m−2 over most of the regions.

Glassform-Version 1: A Spreadsheet or an Algorithm for Generating Preliminary Glass Formulations for Waste Streams

AbstractGLASSFORM-Version 1, a spreadsheet or an algorithm software package, was developed for generating preliminary glass formulations for waste streams. A spreadsheet program on Microsoft Excel 97 for Windows 95 was also developed for predicting key glass properties for laboratory scale vitrification studies of simulated waste streams. The algorithm version based on Modula 2, which can be run on Windows-95 or NT, was developed to plot the glass component ratios versus the waste loading. At this time the algorithm was not developed for predicting the key glass properties. The spreadsheet or the algorithm version is an effective tool for developing preliminary glasses with a potential to be chemically durable, dense for volume reduction, of low viscosity for glass pouring, redox controlled, and resistant to corrosion of melter components such as Inconel 690. For a given solid waste stream oxide composition in wt.% or in grams or in ppm and waste loading in wt.%, the spreadsheet or the algorithm calculates glass component ratios that provide an empirical indication of the quality of a candidate glass. In addition to the component ratios for glass quality indicators, glass property composition relationships for glass durability and processability were incorporated into the spreadsheet version. These spreadsheet or algorithm versions can also be used for studying the effects of such actions as varying waste loadings or of varying individual waste components on glass properties and glass component ratios, provided specific glass property models are incorporated. As an example, the software was applied to candidate phosphate-containing glasses at the Idaho Nuclear Technology and Engineering Center (INTEC, previously Idaho Chemical Processing Plant) and also the borosilicate glasses such as the Savannah River Laboratory Environmental Assessment (EA) glass, the Hanford standard (ARM-1) glass, and the French R7T7 glass. Application of the software to new waste streams such as at Hanford, Fernald, and other countries is the most useful aspect of the GLASSFORM software during the early stages of glass waste form development.

Toward a preliminary macro theory of drug addiction

Currently, the drug addiction literature is replete with micro‐level theories of addiction that offer important insights into individual and small‐group processes leading to addiction. However, few offer much consideration of macro‐level matters (e.g., social structural and cultural). Macro theories of addiction are even more scarce. This inattention to macro‐level factors may ultimately impede the ability to reduce addiction and related social problems. The purpose of this article is to offer preliminary formulations for a macro theory of drug addiction. A critique of leading micro‐oriented theories, coupled with Hall and Jefferson's (1976) Cultural Studies school, helps facilitate this effort. The discussion centers on drug subcultures instead of individual addicts and brings macro‐level matters (e.g., economic and social inequality and cultural norms and values) to the center of the debate. Furthermore, the new theoretical formulations offer important insights into rates of addiction among population s...

An Attempt to Develop a New Fire-Resistant Hydraulic Fluid Based on Water-in-Oil Microemulsions

The strategy for the development of microemulsion-based fire-resistant hydraulic fluids has been expounded. Phase diagrams were constructed for mixtures of water, oil, and nonionic surfactants with and without cosurfactants. From these phase diagrams, the boundaries of the monophasic area were outlined. After the major components had thus been determined, several preliminary formulations were developed by incorporating suitable additives into the oleic ingredient of the hydraulic fluid. These carefully chosen additives considerably improve the performance of the hydraulic fluid. The resulting microemulsion-based compositions complied with most of the requirements set for fire-resistant hydraulic fluids. Model systems pertinent to such formulations were utilized in order to investigate structural factors, which induce enhanced water solubilization. The role played by alcohols in this context was elucidated in terms of an empirical equation. Sophisticated scattering and NMR methods have demonstrated the variations in the microstructure of a high water content model system. Sub-zero differential scanning calorimetry (DSC) techniques have revealed the existence of two types of water (free and bound) and determined their relative concentrations.

Multi-Fault Diagnosis and Recovery by On-Line Consultation of an Expert System

In the framework of a cooperation between the Pont-a-Mousson Resarch Center and the CRIN laboratory, we have designed an expert system for an optimal help in fault processing. The field of investigation concerns a certain category of boilers for central heating and warm water productionIn this paper, we present the general problem of troubleshooting, the expert knowledge transfer phase, the knowledge formalization and the design of the demonstrator, able to treat about fifty possible causes from twenty preliminary formulations of the failure pieces of evidence