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At least 919 records · Page 51Linked to original sources
PubMed2000

Multivariate methods in developing an evolutionary strategy for tablet formulation.

The aim of this study was to develop a new strategy for choosing excipients in tablet formulation. Multivariate techniques such as principal component analysis (PCA) and experimental design were combined in a multivariate design for screening experiments. Of a total 87 investigated excipients, the initial screening experiments contained 5 lubricants, 9 binders, and 5 disintegrants, and 35 experiments were carried out. Considering a reduced factorial design was used, the resulting PCA and partial least squares (PLS) models offered good insight into the possibilities of tablet formulation. It also offered solutions to the problems and clearly gave directions for optimum formulations. Further, it offered several alternatives for achieving quality formulations. Additional experiments conducted to validate and verify the usefulness of the model were successful, resulting in several tablets of good quality. The conclusion is that a multivariate strategy in tablet of formulation is efficient and can be used to reduce the number of experiments drastically. Combining multivariate characterization, physicochemical properties, experimental design, multivariate design, and PLS would lead to an evolutionary strategy for tablet formulation. Since it includes a learning strategy that continuously incorporates data for new compounds and from conducted experiments, this would be an even more powerful tool than expert systems.

Chemistry, Pharmaceutical↗
PubMed2002

Lipid formulation as a drug carrier for drug delivery.

In recent years, a Drug Delivery System (DDS), a preparative approach attracts the attention in the development of new drugs. DDS focuses on the regulation of the in vivo dynamics, such as absorption, distribution, metabolism, and elimination, thereby improving the effectiveness and the safety of the drugs by an applicable use of drug preparation technologies. A conventional intravenous dosage form of Amphotericin B (AmB), Fungizone, is the most effective clinically available for treating fungal infections. However, the clinical efficacy of AmB is limited by its adverse effects. Several lipid formulations, such as Liposomal AmB (L-AmB), AmB lipid complex (ABLC), and AmB colloidal dispersion (ABCD), with reduced side effects have been developed. These formulations are reported to have excellent safety and efficacy. However, comparable efficacy can be achieved only when they are administered at high doses than AmB. One of the problems of using these formulations is that they are easily taken up by the reticuloendothelial system (RES). An artificial lipoprotein-like particles, a novel drug carrier Lipid Nano-Sphere (LNS), which is 25 - 50 nm in size and is composed of phospholipids and simple lipid. LNS show a higher plasma concentration of drugs and lower uptake by RES-tissue different forms other lipid base drug carriers. In vitro and in vivo, LNS incorporating AmB, NS-718, shows reduced toxicity, while maintaining activity against fungi. LNS have a unique characteristic as an effective carrier of AmB for treatment of fungal infection.

Amphotericin B↗
PubMed1977

Bioavailability of digoxin: some pitfalls and problems.

The bioavailability of tablet formulations averages about 60% for digoxin, 75% for beta-acetyldigoxin, and 75% for beta-methyldigoxin. Bioavailability as a measure of the absolute amount reaching the systemic circulation should be calculated from steady state data. Only in steady state does the retarding effect of absorption disappear which diminishes the p.o./i.v. relation of data. For a screening test bioavailability may be calculated from 24-hour renal excretion values after a single dose, performing absolute and relative studies consecutively in cross-over arrangements. The absorption rate constant of digoxin and its derivatives is approximately 0.7 (h-1) which corresponds to an absorption half life of about 1 hour. The absorption rate constant can be calculated from plasma concentration values as well as from renal excretion rates 1 or 2 hours after dosing.

Biological Availability↗
PubMed2002

Quantitative elasticity imaging: what can and cannot be inferred from strain images.

We examine the inverse problem associated with quantitative elastic modulus imaging: given the equilibrium strain field in a 2D incompressible elastic material, determine the elastic stiffness (shear modulus). We show analytically that a direct formulation of the inverse problem has no unique solution unless stiffness information is known a priori on a sufficient portion of the boundary. This implies that relative stiffness images constructed on the assumption of constant boundary stiffness are in error, unless the stiffness is truly constant on the boundary. We show further that using displacement boundary conditions in the forward incompressible elasticity problem leads to a nonunique inverse problem. Indeed, we give examples in which exactly the same strain field results from different elastic modulus distributions under displacement boundary conditions. We also show that knowing the stress on the boundary can, in certain configurations, lead to a well-posed inverse problem for the elastic stiffness. These results indicate what data must be taken if the elastic modulus is to be reconstructed reliably and quantitatively from a strain image.

Computer Simulation↗
PubMed2006

Shapeme histogram projection and matching for partial object recognition.

Histograms of shape signature or prototypical shapes, called shapemes, have been used effectively in previous work for 2D/3D shape matching and recognition. We extend the idea of shapeme histogram to recognize partially observed query objects from a database of complete model objects. We propose representing each model object as a collection of shapeme histograms and match the query histogram to this representation in two steps: 1) compute a constrained projection of the query histogram onto the subspace spanned by all the shapeme histograms of the model and 2) compute a match measure between the query histogram and the projection. The first step is formulated as a constrained optimization problem that is solved by a sampling algorithm. The second step is formulated under a Bayesian framework, where an implicit feature selection process is conducted to improve the discrimination capability of shapeme histograms. Results of matching partially viewed range objects with a 243 model database demonstrate better performance than the original shapeme histogram matching algorithm and other approaches.

Algorithms↗
PubMed1999

Some misconceptions in the kinetic analyses of pharmaceutical systems.

Some problems encountered during the formulation of reaction mechanisms, by the interpretation of kinetic and other experimental observations, in studies of reactions that occur on heating reactants that are initially solid, are critically reviewed. The representative chemical changes selected for inclusion here appear to be relatively simple. It has been found, however, that the provision of acceptable representational models is less straight-forward than might have been anticipated. Accordingly, it is concluded that, when interpreting kinetic data, it is essential to consider most carefully the significance of all experimental measurements in the context of the overall change. Interpretational difficulties, recognised in the literature, that identify inconsistencies that may complicate kinetic analysis are illustrated through consideration of the following systems (and other examples): characterisation of the changes in reaction stoichiometry that result from the presence of a gaseous atmosphere during NiSO4.6H2O dehydration; the sensitivity of kinetic behaviour to reaction conditions during the dehydration of NiC2O4.2H2O and in the dissociation of CaCO3; the formation of intermediates and the possibility of melting during the decompositions of KMnO4 and of copper(II) malonate. It is concluded that the formulation of reaction models through the interpretation of kinetic (with other) data for solid-state decomposition is more difficult than is sometimes acknowledged. It is not known how widely problems of the types described in this short review apply. These are mentioned here as types of behaviour that require more general consideration in kinetic and mechanistic studies of the changes that occur on heating reactants that are originally solid.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Dynamic map labeling.

We address the problem of filtering, selecting and placing labels on a dynamic map, which is characterized by continuous zooming and panning capabilities. This consists of two interrelated issues. The first is to avoid label popping and other artifacts that cause confusion and interrupt navigation, and the second is to label at interactive speed. In most formulations the static map labeling problem is NP-hard, and a fast approximation might have O(nlogn) complexity. Even this is too slow during interaction, when the number of labels shown can be several orders of magnitude less than the number in the map. In this paper we introduce a set of desiderata for "consistent" dynamic map labeling, which has qualities desirable for navigation. We develop a new framework for dynamic labeling that achieves the desiderata and allows for fast interactive display by moving all of the selection and placement decisions into the preprocessing phase. This framework is general enough to accommodate a variety of selection and placement algorithms. It does not appear possible to achieve our desiderata using previous frameworks. Prior to this paper, there were no formal models of dynamic maps or of dynamic labels; our paper introduces both. We formulate a general optimization problem for dynamic map labeling and give a solution to a simple version of the problem. The simple version is based on label priorities and a versatile and intuitive class of dynamic label placements we call "invariant point placements". Despite these restrictions, our approach gives a useful and practical solution. Our implementation is incorporated into the G-Vis system which is a full-detail dynamic map of the continental USA. This demo is available through any browser.

Journal Article↗
PubMed1990

[Histopathology of malignant lymphomas].

Histopathological features of malignant lymphomas were described and discussed. For the standard classification of malignant lymphomas, the Rye classification for Hodgkin's disease and the International Working Formulation for the non-Hodgkin's lymphoma were recommended. Recent advances in immunology make immunophenotyping of lymphoma cells possible. The usefulness of immunophenotyping in routine paraffin sections was suggested. Some problems of the Working Formulation in classifying T-cell lymphomas were also discussed. A significant difference in the 5-year survival between the different histological grades of Working Formulation and between T and B phenotypes was found in a survey using 604 non-Hodgkin's lymphoma cases of our own. It is concluded that precise histological typing and immunophenotyping of lymphomas are mandatory in the diagnosis, treatment and prediction of the prognosis of patients with malignant lymphomas.

B-Lymphocytes↗
PubMed1999

Shape-based nonrigid correspondence with application to heart motion analysis.

A common problem in many biomedical imaging studies is that of finding a correspondence between two plane curves which aligns their shapes. A mathematical formulation and solutions to this problem is proposed in this paper. The formulation exhibits desirable properties. It allows for one-to-one as well as non-one-to-one correspondences, it consistently compares shape, even in nonrigid situations, and it is completely symmetric with respect to the two curves. A numerical implementation of the algorithm for finding the optimal correspondence is also reported. The algorithm is used to estimate nonrigid motion of the endocardium in MRI image sequences of normal and post-infarct dog hearts. The return error (the difference between the starting and ending positions of a point) is used as a performance measure to evaluate the technique. Since heart motion is periodic, the return error is a measure of consistency of the algorithm. Preliminary applications to other data sets are reported as well.

Algorithms↗
PubMed1995

Approximating the effects of diffusion on reversible reactions at the cell surface: ligand-receptor kinetics.

We consider the problem of determining the time dependence of the bound ligand concentration for the reversible binding of a diffusing monovalent ligand to receptors uniformly distributed over the surface of a spherical cell. We start by formulating a boundary value problem that captures the essential physics of this situation. We then introduce a systematic approximation scheme based on the method of weighted residuals. By this means we convert the initial boundary value problem into a simpler problem that requires solving only a small number of ordinary differential equations. We show how, at the lowest order of approximation, the method can be used to obtain modified chemical rate equations where, in place of fundamental rate constants, effective rate coefficients appear. These rate coefficients are functions of the ligand diffusion coefficient, the cell radius, the receptor density and other variables. We compare exact and approximate solutions and discuss under what conditions the approximate equations can be used. We also apply the method of weighted residuals to obtain approximate descriptions of the binding kinetics when (1) there are two different cell surface receptor populations that bind the ligand and (2) the cell secretes a ligand that can bind back to receptors on the cell (autocrine binding).

Biophysical Phenomena↗
PubMed2003

Fast two-frame multiscale dense optical flow estimation using discrete wavelet filters.

A multiscale algorithm with complexity O(N) (where N is the number of pixels in one image) using wavelet filters is proposed to estimate dense optical flow from two frames. Hierarchical image representation by wavelet decomposition is integrated with differential techniques in a new multiscale framework. It is shown that if a compactly supported wavelet basis with one vanishing moment is carefully selected, hierarchical image, first-order derivative, and corner representations can be obtained from the wavelet decomposition. On the basis of this result, three of the four components of the wave let decomposition are employed to estimate dense optical flow with use of only two frames. This overcomes the "flattening-out" problem in traditional pyramid methods, which produce large errors when low-texture regions become flat at coarse levels as a result of blurring. A two-dimensional affine motion model is used to formulate the optical flow problem as a linear system, with all resolutions simultaneously (i.e., coarse-and-fine) rather than the traditional coarse-to-fine approach, which unavoidably propagates errors from the coarse level. This not only helps to improve the accuracy but also makes the hardware implementation of our algorithm simple. Experiments on different types of image sequences, together with quantitative and qualitative comparisons with several other optical flow methods, are given to demonstrate the effectiveness and the robustness of our algorithm.

Journal Article↗
PubMed1986

Pain cocktails: survey of formulations used in US hospitals.

Brompton's cocktail is an oral formulation used widely for intractable pain associated with cancer. In the United States, however, formulations are not standard, and questions concerning the efficacy and safety of some ingredients have been raised. Hospitals were surveyed to determine the formulation of Brompton's cocktail used, how the cocktail is compounded, and who is responsible for deciding on the pain cocktail formula. Controversy surrounding the use of cocaine as an ingredient is discussed, and problems with dating of formulations are described. P & T Committees are encouraged to review the literature concerning pain cocktail formulations and reevaluate the use of pain cocktails within their own institutions.

Analgesics↗
PubMed2001

A virtual classroom for undergraduate periodontology: a pilot study.

The Integrated Distributed Learning Environments or virtual classrooms constitute a new promising structure in education of health care personnel. A virtual classroom was developed aiming to teach periodontology to an international group of 28 dental students using a problem-based learning (PBL) approach. The course was web-based and included synchronous and asynchronous communication, on-line libraries and multimedia material. Students were organised in 4 independent groups and each group was appointed a tutor. The results of the study indicate that one of the most positive effects students experienced was competence in using the computer. They also rated highly the use of multimedia for learning of clinical procedures. It was found that web boards and email were too slow to allow group work in the virtual classroom. Real time communication programs were found to be superior for problem discussion and hypothesis formulation. However, email and the web board played a significant role during certain steps of the PBL method. The students expressed a positive attitude for the combined use of network-based learning and problem-based education. Our present experience suggests that distance learning should be organised with a mixture of different media, allowing communication of knowledge and skills between the resources and the students, as well as cooperation between the students. Computer literacy among teachers and students is limited and should be enhanced. Finally, personal contact between the resource persons and the students before the distant learning course commences helps the learning process.

Attitude↗
PubMed2006

Multivariate methods in the development of a new tablet formulation: excipient mixtures and principal properties.

A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material. The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents). As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.

Chemistry, Pharmaceutical↗
PubMed2004

Towards multifunctional synthetic vectors.

Recent progress on the fronts of design, formulation and delivery with synthetic vectors has increased the potential of non-viral approaches to attain therapeutic applications. However, a number of hurdles remain to be cleared. On the one hand, we have the problem of producing and formulating stable, diffusible complexes and on the other hand, we have to face the fact that in vivo delivery is probably too complex and multifaceted to be achieved successfully with a single carrier molecule in most instances. This review concentrates on this latter aspect and the design of artificial multi-component vectors aimed at providing solutions to membrane crossing, endosomal escape and navigation through the nuclear pore. In many instances the solutions proposed have been inspired by natural mechanisms exploited by bacteria and viruses. However, entirely novel chemical approaches such as monomolecular DNA condensation via detergent dimerization, or endosome disruption by osmotic swelling, are also being investigated and developed. The combination of these naturally inspired and chemically-originated approaches is bringing us continually closer to the concept of constructing an artificial virus capable of delivering viable nucleic acid-based pharmaceuticals to defined cells in vivo. This review considers the most successful current solutions to the main biological barriers to gene delivery including appropriate DNA compaction, cell targeting and entry, vacuole escape, nuclear import and in vivo delivery. In the latter section, emphasis is placed on one of the most versatile non-viral vectors currently available, linear polyethylenimine.

Active Transport, Cell Nucleus↗
PubMed1984

Calculation of absorbed power in tissue for various hyperthermia devices.

Recently, there has been increased interest in the use of hyperthermia (temperatures, 42 to 45 degrees) as an adjuvant modality to radiation therapy or chemotherapy for the treatment of cancer. This paper discusses the use of the finite element method as a technique for calculating the power deposited per unit volume of tissue for two regional-type hyperthermia devices. The two types of devices investigated are inductive concentric coils and annular phased arrays. The mathematical basis for the finite element method and its advantages when dealing with problems involving irregular boundaries and nonhomogeneous tissue are reviewed. Specific examples are shown for the calculations of the electromagnetic fields and the resulting absorbed power density. Furthermore, it is shown how the basic finite element formulation for the electromagnetic problem can be extended to solving the temperature distribution problem. Temperature distributions for both types of devices are illustrated. Finally, the limitations of the finite element method are reviewed, and possible implications of the specific results for the efficacy of regional devices are raised.

Body Temperature↗
PubMed1994

Biopharmaceutical aspects of tolfenamic acid.

The pharmacokinetics of tolfenamic acid is well described by a two-compartment model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid is highly protein-bound with small volumes of distribution. It is cleared relatively fast (150-200 ml/min), mainly by hepatic metabolism and the metabolites are renally cleared as glucuronic acid conjugates. The peroral absorption is good and the peroral bioavailability is about 75%, as first pass metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the second dose is observed. The bioavailability in dependence of age and disease has been studied and only in the case of severe liver or kidney impairment, a change in dosage regimen seems warranted. The development of different formulations will be outlined, mainly on rectal delivery, on sustained release and rapid release oral formulations, on topical ointment, and on parenteral delivery. The problems with tolfenamic acid in pharmaceutical formulation caused mainly by poor solubility will be discussed. Formulations ready for the market now or very soon are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral formulations need further development to be ready for marketing in the years to come.

Absorption↗