Challenges and emerging solutions in the development of compressed orally disintegrating tablets

Areas covered: The review discusses the main challenges of ODT manufacturing process and the emerging solutions featured at early drug development stages. The research specifically describes the methods reported for taste masking/assessment and solubilisation of unpalatable and poorly soluble drugs, respectively. Furthermore, this review highlights the techniques used for developing modified-release ODTs, an emerging area in the field. In addition, it also discusses the poor flowability and segregation problems of directly compressed powders. Moreover, the review describes the tests reported in the literature for ODT disintegration time assessment since a universal technique is still non-existent. Expert opinion: The approaches used to overcome the manufacturing challenges often have a bearing on the price of the end product. However, despite the technical and regulatory challenges, ODTs can offer many advantages over the conventional dosage forms if accompanied by suitable adjuvant technologies and in vitro analytical tools. © 2014 Informa UK, Ltd. Introduction: Orally disintegrating tablets (ODTs) provide several advantages over conventional tablets such as suitability for patients with swallowing difficulties and faster onset of action. The manufacture of ODTs by compression/tableting offers a practical and cost-effective strategy over the freeze drying (lyophilisation) method. Nonetheless, the FDA recommends a disintegration time of 30 s and a maximum weight of 500 mg for a tablet to be labelled as an ODT. These requirements, alongside other desirable product properties, have created a number of challenges for the formulator to overcome while developing compressed ODTs.

Adoption of e-business solutions in food supply chains

The aim of this chapter is to increase understanding of e-business adoption in the food supply chain. In the first part of the paper an analysis of the concept and the context of e-business are presented along with a classification of the various e-business applications based on the dimensions of involvement and complexity. Next emphasis is given to the issue of e-business adoption. In particular an analysis of the factors that influence the adoption process is provided by exploring the specific characteristics of the food industry as well as the potential impact of the use of e-business solutions. These factors are not only related to the company but also to the supply chain of each company and the actual value of e-business applications. The chapter concludes that in many cases e-business is wrongly considered as a sole application and its adoption as mainly an intra-firm issue. Finally future trends are considered and discussed. © 2010 Woodhead Publishing Limited All rights reserved.

Comments on multiple oscillatory solutions in systems with time-delay feedback

A complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms is considered. In particular, multiple oscillatory solutions and their properties are studied. We present novel results regarding the disappearance of limit cycle solutions, derive analytical criteria for frequency degeneration, amplitude degeneration, frequency extrema. Furthermore, we discuss the influence of the phase shift parameter and show analytically that the stabilization of the steady state and the decay of all oscillations (amplitude death) cannot happen for global feedback only. Finally, we explain the onset of traveling wave patterns close to the regime of amplitude death.

The application of fixed hydrophobic patterns for confinement of aqueous solutions in proteomic microarrays

A protein microarray hybridisation system has been implemented by employing patterned hydrophobic thin films on hydrophilic substrates as a means of confinement for aqueous samples. This approach has the ability to handle, and keep separate, small sample volumes of just a few microlitres. In addition, the system is more straightforward to use than the existing multi-well gasket solution. The paper describes the fabrication method and the system is demonstrated for a model protein microarray assay. © 2011 American Institute of Physics.

Stokes waves revisited:exact solutions in the asymptotic limit

The Stokes perturbative solution of the nonlinear (boundary value dependent) surface gravity wave problem is known to provide results of reasonable accuracy to engineers in estimating the phase speed and amplitudes of such nonlinear waves. The weakling in this structure though is the presence of aperiodic “secular variation” in the solution that does not agree with the known periodic propagation of surface waves. This has historically necessitated increasingly higher-ordered (perturbative) approximations in the representation of the velocity profile. The present article ameliorates this long-standing theoretical insufficiency by invoking a compact exact n-ordered solution in the asymptotic infinite depth limit, primarily based on a representation structured around the third-ordered perturbative solution, that leads to a seamless extension to higher-order (e.g., fifth-order) forms existing in the literature. The result from this study is expected to improve phenomenological engineering estimates, now that any desired higher-ordered expansion may be compacted within the same representation, but without any aperiodicity in the spectral pattern of the wave guides.

A study of magnetic non-linearity and finite length effects in solid iron subjected to a travelling MMF wave

This thesis describes an experimental and analytic study of the effects of magnetic non-linearity and finite length on the loss and field distribution in solid iron due to a travelling mmf wave. In the first half of the thesis, a two-dimensional solution is developed which accounts for the effects of both magnetic non-linearity and eddy-current reaction; this solution is extended, in the second half, to a three-dimensional model. In the two-dimensional solution, new equations for loss and flux/pole are given; these equations contain the primary excitation, the machine parameters and factors describing the shape of the normal B-H curve. The solution applies to machines of any air-gap length. The conditions for maximum loss are defined, and generalised torque/frequency curves are obtained. A relationship between the peripheral component of magnetic field on the surface of the iron and the primary excitation is given. The effects of magnetic non-linearity and finite length are combined analytically by introducing an equivalent constant permeability into a linear three-dimensional analysis. The equivalent constant permeability is defined from the non-linear solution for the two-dimensional magnetic field at the axial centre of the machine to avoid iterative solutions. In the linear three-dimensional analysis, the primary excitation in the passive end-regions of the machine is set equal to zero and the secondary end faces are developed onto the air-gap surface. The analyses, and the assumptions on which they are based, were verified on an experimental machine which consists of a three-phase rotor and alternative solid iron stators, one with copper end rings, and one without copper end rings j the main dimensions of the two stators are identical. Measurements of torque, flux /pole, surface current density and radial power flow were obtained for both stators over a range of frequencies and excitations. Comparison of the measurements on the two stators enabled the individual effects of finite length and saturation to be identified, and the definition of constant equivalent permeability to be verified. The penetration of the peripheral flux into the stator with copper end rings was measured and compared with theoretical penetration curves. Agreement between measured and theoretical results was generally good.

Characterization of a volume-sensitive chloride current in rat osteoblast-like (ROS 17/2.8) cells

1. During osmotic swelling, cultured osteoblastic cells (ROS 17/2.8) exhibited activation of large amplitude Cl- currents in the whole-cell configuration of the patch-clamp technique. Effects of hypotonic shock on cell volume and membrane conductance were rapidly reversed on return to isotonic conditions. 2. Voltage command pulses in the range -80 to +50 mV produce instantaneous activation of Cl- currents. At potentials more positive than +50 mV the current exhibited time-dependent inactivation. The instantaneous current-voltage relationship was outwardly rectifying. 3. The anion permeability sequence of the induced current was SCN- (2.2) > I- (1.9) > Br- (1.5) > Cl- (1.0) > F- (0.8) > gluconate- (0.2). This corresponds to Eisenman's sequence I. 4. The volume-sensitive Cl- current was effectively inhibited by the Cl- channel blockers 4,4'-diisothiocyanatostilbene-2,2-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). Outward currents were more effectively suppressed by DIDS than inward currents. The concentrations for 50% inhibition (IC50) of outward and inward currents were 81 and 298 μM, respectively. NPPB was equally effective at inhibiting outward and inward currents (IC50 of 64 μM). The current was relatively insensitive to diphenylamine-2-carboxylate (DPC), 500 μM producing only 22.5 ± 4.0% inhibition. 5. Inhibitors of protein kinase A (H-89, 1 μM) and tyrosine kinase (tyrphostin A25, 200 μM) were without effect upon activation of Cl- currents in response to hypotonic shock. Under isotonic conditions, elevation of intracellular Ca2+ by ionomycin (1 μM) or activation of protein kinase C by 12-O-tetradecanoylphorbol 13-acetate (TPA, 0.1 μM) failed to evoke increases in basal Cl- conductance levels. 6. It is concluded that an outwardly rectifying Cl- conductance is activated upon osmotic swelling and may be involved in cell volume regulation of ROS 17/2.8 cells.

Premium e-grocery:exploring value in logistics integrated service solutions

E-grocery is gradually becoming viable or a necessity for many families. Yet, most e-supermarkets are seen as providers of low value "staple" and bulky goods mainly. While each store has a large number of SKU available, these products are mainly necessity goods with low marginal value for hedonistic consumption. A need to acquire diverse products (e.g., organic), premium priced products (e.g., wine) for special occasions (e.g., anniversary, birthday), or products just for health related reasons (e.g., allergies, diabetes) are yet to be served via one-stop e-tailers. In this paper, we design a mathematical model that takes into account consumers' geo-demographics and multi-product sourcing capacity for creating critical mass and profit. Our mathematical model is a variant of Capacitated Vehicle Routing Problem with Time Windows (CVRPTW), which we extend by adding intermediate locations for trucks to meet and exchange goods. We illustrate our model for the city of Istanbul using GIS maps, and discuss its various extensions as well as managerial implications.

A CFD approach on the effect of particle size on char entrainment in bubbling fluidised bed reactors

The fluid – particle interaction inside a 41.7 mg s-1 fluidised bed reactor is modelled. Three char particles of sizes 500 µm, 250 µm, and 100 µm are injected into the fluidised bed and the momentum transport from the fluidising gas and fluidised sand is modelled. Due to the fluidising conditions and reactor design the char particles will either be entrained from the reactor or remain inside the bubbling bed. The particle size is the factor that differentiates the particle motion inside the reactor and their efficient entrainment out of it. A 3-Dimensional simulation has been performed with a completele revised momentum transport model for bubble three-phase flow according to the literature as an extension to the commercial finite volume code FLUENT 6.2.

Use of computational fluid dynamics in the design of bubble column reactors

Investigations into the modelling techniques that depict the transport of discrete phases (gas bubbles or solid particles) and model biochemical reactions in a bubble column reactor are discussed here. The mixture model was used to calculate gas-liquid, solid-liquid and gasliquid-solid interactions. Multiphase flow is a difficult phenomenon to capture, particularly in bubble columns where the major driving force is caused by the injection of gas bubbles. The gas bubbles cause a large density difference to occur that results in transient multi-dimensional fluid motion. Standard design procedures do not account for the transient motion, due to the simplifying assumptions of steady plug flow. Computational fluid dynamics (CFD) can assist in expanding the understanding of complex flows in bubble columns by characterising the flow phenomena for many geometrical configurations. Therefore, CFD has a role in the education of chemical and biochemical engineers, providing the examples of flow phenomena that many engineers may not experience, even through experimentation. The performance of the mixture model was investigated for three domains (plane, rectangular and cylindrical) and three flow models (laminar, k-e turbulence and the Reynolds stresses). mThis investigation raised many questions about how gas-liquid interactions are captured numerically. To answer some of these questions the analogy between thermal convection in a cavity and gas-liquid flow in bubble columns was invoked. This involved modelling the buoyant motion of air in a narrow cavity for a number of turbulence schemes. The difference in density was caused by a temperature gradient that acted across the width of the cavity. Multiple vortices were obtained when the Reynolds stresses were utilised with the addition of a basic flow profile after each time step. To implement the three-phase models an alternative mixture model was developed and compared against a commercially available mixture model for three turbulence schemes. The scheme where just the Reynolds stresses model was employed, predicted the transient motion of the fluids quite well for both mixture models. Solid-liquid and then alternative formulations of gas-liquid-solid model were compared against one another. The alternative form of the mixture model was found to perform particularly well for both gas and solid phase transport when calculating two and three-phase flow. The improvement in the solutions obtained was a result of the inclusion of the Reynolds stresses model and differences in the mixture models employed. The differences between the alternative mixture models were found in the volume fraction equation (flux and deviatoric stress tensor terms) and the viscosity formulation for the mixture phase.

The temperature dependence of the electro-optic kerr effect in solutions

A novel Kerr cell of greater optical path length and temperature stability has been designed and built. The Kerr effect experimental has been substantially automated using an Apple IIe computer. Software has been written allowing the computer to partially control the Kerr effect equipment and to acquire and analyse the relevant data.The temperature dependent electro-optic Kerr effect of 2-methyl-4-nitroaniline, p-nitroaniline, nitrobenzene, aniline, and toluene as solutions in 1, 4-dioxane has been studied. The Kerr effect measurements combined with dipole moment, depolarisation ratio, dielectric, and electronic polarisation measurements have been used to calculate the first hyperpolarisability of the solute.Although first hyperpolarisabilities for the compounds studied have been measured in various physical states using a variety of experimental techniques, it is gratifying to find that the values presented in this thesis have a linear relationship with values reported by other workers.

Comparative performance of analytical techniques for polyhexamethylene biguanide (PHMB) in ophthalmic solutions

Purpose: The use of PHMB as a disinfectant in contact lens multipurpose solutions has been at the centre of much debate in recent times, particularly in relation to the issue of solution induced corneal staining. Clinical studies have been carried out which suggest different effects with individual contact lens materials used in combination with specific PHMB containing care regimes. There does not appear to be, however, a reliable analytical technique that would detect and quantify with any degree of accuracy the specific levels of PHMB that are taken up and released from individual solutions by the various contact lens materials. Methods: PHMB is a mixture of positively charged polymer units of varying molecular weight that has maximum absorbance wavelength of 236 nm. On the basis of these properties a range of assays including capillary electrophoresis, HPLC, a nickelnioxime colorimetric technique, mass spectrophotometry, UV spectroscopy and ion chromatography were assessed paying particular attention to each of their constraints and detection levels. Particular interest was focused on the relative advantage of contactless conductivity compared to UV and mass spectrometry detection in capillary electrophoresis (CE). This study provides an overview of the comparative performance of these techniques. Results: The UV absorbance of PHMB solutions, ranging from 0.0625 to 50 ppm was measured at 236 nm. Within this range the calibration curve appears to be linear however, absorption values below 1 ppm (0.0001%) were extremely difficult to reproduce. The concentration of PHMB in solutions is in the range of 0.0002–0.00005% and our investigations suggest that levels of PHMB below 0.0001% (levels encountered in uptake and release studies) can not be accurately estimated, in particular when analysing complex lens care solutions which can contain competitively absorbing, and thus interfering, species in the solution. The use of separative methodologies, such as CE using UV detection alone is similarly limited. Alternative techniques including contactless conductivity detection offer greater discrimination in complex solutions together with the opportunity for dual channel detection. Preliminary results achieved by TraceDec1 contactless conductivity detection, (Gain 150%, Offset 150) in conjunction with the Agilent capillary electrophoresis system using a bare fused silica capillary (extended light path, 50 mid, total length 64.5 cm, effective length 56 cm) and a cationic buffer at pH 3.2, exhibit great potential with reproducible PHMB split peaks. Conclusions: PHMB-based solutions are commonly associated with the potential to invoke corneal staining in combination with certain contact lens materials. However this terminology ‘PHMBbased solution’ is used primarily because PHMB itself has yet to be adequately implicated as the causative agent of the staining and compromised corneal cell integrity. The lack of well characterised adequately sensitive assays, coupled with the range of additional components that characterise individual care solutions pose a major barrier to the investigation of PHMB interactions in the lenswearing eye.

Protein-protein interactions in ovalbumin solutions studied by small angle scattering: effect of ionic strength, and the chemical nature of cations

The influence of ionic strength and of the chemical nature of cations on the protein-protein interactions in ovalbumin solution was studied using small-angle X-ray and neutron scattering (SAXS/SANS). The globular protein ovalbumin is found in dimeric form in solutions as suggested by SANS/SAXS experiments. Due to the negative charge of the proteins at neutral pH, the protein-protein interactions without any salt addition are dominated by electrostatic repulsion. A structure factor related to screened Coulombic interactions together with an ellipsoid form factor was used to fit the scattering intensity. A monovalent salt (NaCl) and a trivalent salt (YCl3) were used to study the effect of the chemical nature of cations on the interaction in protein solutions. Upon addition of NaCl, with ionic strength below that of physiological conditions (150 mM), the effective interactions are still dominated by the surface charge of the proteins and the scattering data can be understood using the same model. When yttrium chloride was used, a reentrant condensation behavior, i.e., aggregation and subsequent redissolution of proteins with increasing salt concentration, was observed. SAXS measurements reveal a transition from effective repulsion to attraction with increasing salt concentration. The solutions in the reentrant regime become unstable after long times (several days). The results are discussed and compared with those from bovine serum albumin (BSA) in solutions.

Intermediate asymptotics in nonlinear optical systems

Using a fiber laser system as a specific illustrative example, we introduce the concept of intermediate asymptotic states in finite nonlinear optical systems. We show that intermediate asymptotics of nonlinear equations (e.g., coherent structures with a finite lifetime or distance) can be used in applications similar to those of truly stable asymptotic solutions, such as, e.g., solitons and dissipative nonlinear waves. Applying this general idea to a particular, albeit practically important, physical system, we demonstrate a novel type of nonlinear pulse-shaping regime in a mode-locked fiber laser leading to the generation of linearly chirped pulses with a triangular distribution of the intensity.

Intermediate asymptotics in nonlinear optical systems

Using a fiber laser system as a specific illustrative example, we introduce the concept of intermediate asymptotic states in finite nonlinear optical systems. We show that intermediate asymptotics of nonlinear equations (e.g., coherent structures with a finite lifetime or distance) can be used in applications similar to those of truly stable asymptotic solutions, such as, e.g., solitons and dissipative nonlinear waves. Applying this general idea to a particular, albeit practically important, physical system, we demonstrate a novel type of nonlinear pulse-shaping regime in a mode-locked fiber laser leading to the generation of linearly chirped pulses with a triangular distribution of the intensity.