Biomedical subjects

Ashutosh Sharma

Publications and source records attributed to Ashutosh Sharma.

At least 19 recordsLinked to original sources

PubMed2006

In vitro and in vivo evaluation of the transdermal iontophoretic delivery of sumatriptan succinate.

The objective was to evaluate the transdermal delivery of the 5-HT(1B/1D) agonist, sumatriptan from an iontophoretic patch system, in vivo. Initial in vitro experiments were conducted to optimize formulation parameters prior to iontophoretic delivery in Yorkshire swine. It was found in vitro that increasing drug load in the patch from 9.7 to 39 mg had no statistically significant effect on cumulative delivery (cf. 305.6+/-172.4 vs. 389.4+/-80.4 microg cm(-2), respectively). However, for a given drug load (39 mg) increasing formulation pH from pH 4.7 to 6.8 significantly increased the cumulative amount of sumatriptan delivered across the skin (389.4+/-80.4 vs. 652.4+/-94.2 microg cm(-2)). A biphasic current profile comprising intensities of 1.8 mA from t=0 to t=180 min and 0.8 mA from t=181 min to t=360 min was used for the in vivo experiments. Drug levels in the blood were 13.7+/-4.5 and 53.6+/-10.2 ng ml(-1) at the 30 and 60 min time-points, rising to 90-100 ng ml(-1) during the 90-180 min time-period. The in vivo results show that the pharmacokinetics following transdermal iontophoretic delivery are comparable to those after oral, nasal or rectal administration, but do not match those upon subcutaneous injection.

Administration, Cutaneous↗

PubMed2006

Nonlinear instabilities and pathways of rupture in thin liquid bilayers.

A long-wave nonlinear analysis of dewetting of thin (<100 nm) liquid bilayers on solid substrates is presented. The short and the long time dynamics, interfacial morphologies, and the pathways of rupture and dewetting are studied to assess the roles of interfacial energies, film thicknesses, and viscosities. The twin interfaces (liquid-liquid and liquid-air) of bilayers under the influence of attractive van der Waals forces show a variety of dewetting pathways which, depending on the interfacial energies and film thicknesses, initially start with one of the two basic modes of instability--in-phase bending and out-of-phase squeezing. These short time modes of evolution and the extent of relative deformations at the interfaces are predicted from the linear stability analysis and verified by the nonlinear simulations. Simulations also show that in the later nonlinear regime, the intermolecular and viscous forces can profoundly modify the initial mode of instability and its growth rate leading to different pathways of dewetting and late stage morphologies. The complex late time patterns such as embedded droplets, inversion of top and bottom phases, and encapsulation of one fluid into the other are also engendered by tuning the intermolecular forces.

Chemistry, Physical↗

PubMed2006

Control of self-organized contact instability and patterning in soft elastic films.

The surface of a soft elastic film becomes unstable and forms a labyrinth pattern when a rigid flat plate is brought into adhesive contact, without application of any external pressure. These isotropic undulations have a characteristic wavelength, lambda approximately 3H, where H is the film thickness. We present here technique of ordering, aligning, and modulating these micro-labyrinth structures by using a patterned stamp, by varying the stamp-film inter-surface distance, by a lateral confinement of the instability and even by a simple shear motion of a flat stamp. Many complex structures, such as an array of femto-liter beakers and doubly periodic channels, are generated from a simple stamp consisting of parallel channels. The elastic nature of the patterns allows an in-situ tuning, manipulation, and reconfiguration of the microstructures. Regardless of their precise morphology, the structures continue to have the elastic length scale, lambda approximately 3H. The structures can also be made permanent as required by UV-ozone-induced oxidation of the structures. The underlying principles of the elastic contact instability presented here have the potential to develop into a new soft lithography technique-elastic contact lithography (ECL), allowing a simple, rapid and large area patterning of soft solids.

Journal Article↗

PubMed2006

Contact instability in adhesion and debonding of thin elastic films.

Based on experiments and 3D simulations, we show that a soft elastic film during adhesion and debonding from a rigid flat surface undergoes morphological transitions to pillars, labyrinths, and cavities, all of which have the same lateral pattern length scale, lambda close to lambda/H approximately 3 for thick films, H > 1 microm . The linear stability analysis and experiments show a new thin film regime where lambda/H approximately equal to 3 + 2pi(lambda/3 muH)1/4 (gamma is surface tension, mu is shear modulus) because of a significant surface energy penalty (for example, lambda/H approximately equal to 6 for H = 200 nm; mu = 1 MPa).

Adhesiveness↗

PubMed2006

Microprocessor controlled transdermal drug delivery.

Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

Administration, Cutaneous↗

PubMed2005

Spinodal instability and pattern formation in thin liquid films confined between two plates.

The instability, morphology and pattern formation engendered by the van der Waals force in a thin liquid film of thickness h confined between two closely placed solid surfaces (at distance d > h) are investigated based on nonlinear 3D simulations. The initial and the final stages of dewetting and pattern formation are found to be crucially dependent on the volumetric (thickness) ratio of air and liquid and its deviation from the location of the maximum of the spinodal parameter versus volumetric ratio curve. On a low energy surface, relatively thinner films and wider air gaps favor initial dewetting of the lower plate by the formation of holes, whereas thicker films with thinner air gaps initially evolve by the formation of columns/bridges that join the upper plate. In the later stage of evolution, the initial holes in thinner films evolve into columns/drops, while a rapid coalescence of columns in the thicker films eventually causes formation of holes. Thus, a phase inversion, either from liquid-in-air to air-in-liquid dispersion or vice versa, occurs during the final stages of evolution. A thin film confined between two high-energy solid surfaces forms columns (bridges) only when its mean thickness, h0, is greater than a critical thickness (hc) or the air gap is smaller than a critical distance. The patterns can be aligned by using a topographically patterned confining surface. Conditions on pattern periodicity, amplitude, and the volumetric ratio of air and liquid in the gap are explored for the formation of various types of ordered patterns including annular rings of columns, concentric ripples, parallel channels and a rectangular array of complex features. The results are of significance in soft lithographies such as LISA, soft stamping and capillary force lithography.

Journal Article↗

PubMed2005

Electric field induced instability and pattern formation in thin liquid films.

Electrostatic field induced instability, morphology, and patterning of a thin liquid film confined between two electrodes with an air gap are studied on the basis of nonlinear 3D simulations, both for spatially homogeneous and heterogeneous fields. In addition to the spinodal flow resulting from the variation of field because of local thickness changes, a heterogeneous imposed field also moves the liquid from the regions of low field to high field, thus allowing a more precise control of pattern. Hexagonal packing of liquid columns is observed for a spatially homogeneous electric field, which is in accord with the e-field experiments on thin polymer films (Schaffer et al. Nature 2000, 403, 874). For a large liquid volume fraction in the gap, varphi > or = 0.75, the coalescence of columns causes a phase inversion, leading to the formation of air columns or cylindrical holes trapped in the liquid matrix (air-in-liquid dispersion). Locally ordered aligned patterns are formed by imposing a spatial variation of the electrostatic field by using a topographically patterned electrode. For example, multiple rows/lines of liquid columns are formed near the edge of a step-like heterogeneity of the electrode and annular rings of ordered columns or concentric ripples are formed around a heterogeneous circular patch. Simulations predict that the electrode pattern is replicated in the film only when the pattern periodicity, L(p), exceeds the instability length scale on the basis of the minimum interelectrode separation distance, L(p) > or = lambda(m)-d(min). Thus, the formation of secondary structures can be suppressed by employing an electrode with deep grooves and stronger field gradients, which produces almost ideal templating. The number density of the electric field induced patterns can be altered by tuning the mean film thickness (or the volume fraction of liquid in the gap), periodicity and depth (amplitude) of the grooves on the top electrode, and the applied voltage. The implications are in electrostatic lithography, pattern replication in soft materials, and the design and interpretation of thin film experiments involving electric fields.

Computer Simulation↗

PubMed2005

Adhesion and debonding of soft elastic films: crack patterns, metastable pathways, and forces.

We study the phenomenon of debonding in a thin soft elastic film sandwiched between two rigid plates as one of the plates is brought into intimate contact and then pulled away from contact proximity by application of a normal force. Nonlinear simulations based on minimization of total energy (composed of stabilizing elastic strain energy and destabilizing adhesive interaction energy) are employed to address the problems of contact hysteresis, cavitation, crack morphology, variation of contact area, snap-off distance, pull-off force, work done, and energy loss. Below a critical distance (d(c)) upon approach, simulations show the formation of columnar structures and nonrandom, regularly arranged nanocavities at the soft interface at a length scale of approximately 3h (h being the thickness of the film). The persistence of such instability upon withdrawal (distance >>d(c)) indicates a contact hysteresis, which is caused by an energy barrier that separates the metastable states of the patterned configuration and the global minimum state of the flat film. The energy and the pull-off force are found to be nonequilibrium and nonunique properties depending on the initial contact, defects, noise, etc. Three broad pathways of debonding leading to adhesive failure of the interface, depending on the stiffness of the film, step size of withdrawal, and the imposed noise, are identified: a catastrophic column collapse mode, a peeling mode involving a continuous decrease in the contact area, and a column splitting mode. The first two modes are caused by a very high stress concentration near the cavity edges. These metastable patterned configurations engender pull-off forces that are orders of magnitude smaller than that required to separate two flat surfaces from contact.

Journal Article↗

PubMed2004

Pattern formation and dewetting in thin films of liquids showing complete macroscale wetting: from "pancakes"to "swiss cheese".

Based on the complete 3D numerical solutions of the nonlinear thin film equation, we address the problems of surface instability, dynamics, morphological diversity and evolution in unstable thin films of the liquids that display complete macroscale wetting. The twin constraints of complete macroscale wettability and nanoscale instability produce a variety of microscopic morphological phases approximating sharp crystal surfaces with flat tops resembling a mesa or a micro "pancake" or a slice of Swiss cheese. While the maximum thickness of flat regions is found to be independent of the initial film thickness, the precise lateral morphology of microdomains formed depends on the film thickness. As the film thickness is increased, the initial pathway of evolution changes from the formation of small spherical droplets, to long mesas (parapets) and islands, to circular holes, all of which eventually resolve by ripening into a collection of round pancakes at equilibrium. However, beyond a certain transition thickness, a novel metastable honeycombed morphology, resembling a membrane or a slice of Swiss cheese, is uncovered, which is produced by an abrupt "freezing" of the evolution during hole growth. In contrast, the spinodal dewetting in thin films of partially wettable systems always engenders spherical droplets at equilibrium. The equilibrium dewetted area from simulations, as well as from simple mass balance, is shown to decline linearly with the initial film thickness.

Journal Article↗

PubMed2004

Influenza and the winter increase in mortality in the United States, 1959-1999.

In economically developed countries, mortality increases distinctly during winter. Many causes have been suggested, including light-dark cycles, temperature/weather, and infectious agents. The authors analyzed monthly mortality in the United States during the period 1959-1999 for four major disease classes. The authors isolated the seasonal component of mortality by removing trends and standardizing the time series. They evaluated four properties: coincidence in mortality peaks, autocorrelation structure and autoregressive integrated moving average (ARIMA) models, magnitude, and age distribution. Peak months of mortality for ischemic heart disease, cerebrovascular disease, and diabetes mellitus coincided appropriately with peaks in pneumonia and influenza, and coefficients of autocorrelation and ARIMA models were essentially indistinguishable. The magnitude of the seasonal component was highly correlated with traditional measures of excess mortality and was significantly larger in seasons dominated by influenza A(H2N2) and A(H3N2) viruses than in seasons dominated by A(H1N1) or B viruses. There was an age shift in mortality during and after the 1968/69 pandemic in each disease class, with features specific to influenza A(H3N2). These findings suggest that the cause of the winter increase in US mortality is singular and probably influenza. Weather and other factors may determine the timing and modulate the magnitude of the winter-season increase in mortality, but the primary determinant appears to be the influenza virus.

Aged↗

PubMed2004

Instability of the interface between thin fluid films subjected to electric fields.

The effect of an externally applied electric field on the stability of the interface between two thin leaky dielectric fluid films of thickness ratio and viscosity ratio ris analyzed using a linear stability analysis in the long-wave limit. A systematic asymptotic expansion is employed in this limit to derive the coupled nonlinear differential equations describing the evolution of the position of the interface between the fluids and the interfacial free charge distribution. The linearized stability of these equations is determined and the effect of the ratio of the conductivities, dielectric constants, thicknesses, and viscosities on the wavenumber of the fastest growing mode, kmax, and the growth rate of the most unstable mode, smax, is examined in detail. Specific configurations considered in previous studies, such as a perfect dielectric-air interface, leaky dielectric-air interface, etc., emerge as limiting cases from the general formulation developed in this paper. Our results show that the viscosity ratio, mur, does not have any significant effect on kmax for the interface between perfect and leaky dielectric fluids. In marked contrast, however, mur is shown to have a significant effect on the interface between two leaky dielectrics. Increasing mur from 0.1 to 10 could decrease kmax up to a factor of 5. In general, our results show that the presence of nonzero conductivity in either one or both of the fluids has a profound influence on the length-scale characteristic of the linear instability: a reduction even by a factor of 1/50 in the length scale can be effected when compared to the interface between two perfect dielectrics. These predictions could have important implications in pattern formation applications in thin fluid films that employ electric fields. The variation of kmax and smax on the thickness ratio, beta, indicates in general that kmaxalpha(beta-apha), and smaxalpha(beta-theta), where the exponents alpha and theta (both >0) are found to depend only on the ratio of conductivities, and are largely independent of other system parameters.

Journal Article↗

PubMed2004

Pervaporation from a dense membrane: roles of permeant-membrane interactions, Kelvin effect, and membrane swelling.

Dense polymeric membranes with extremely small pores in the form of free volume are used widely in the pervaporative separation of liquid mixtures. The membrane permeation of a component followed by its vaporization on the opposite face is governed by the solubility and downstream pressure. We measured the evaporative flux of pure methanol and 2-propanol using dense membranes with different free volumes and different affinities (wettabilities and solubilities) for the permeant. Interestingly, the evaporative flux for different membranes vanished substantially (10-75%) below the equilibrium vapor pressure in the bulk. The discrepancy was larger for a smaller pore size and for more wettable membranes (higher positive spreading coefficients). This observation, which cannot be explained by the existing (mostly solution-diffusion type) models ofpervaporation, suggests an important role for the membrane-permeant interactions in nanopores that can lower the equilibrium vapor pressure. The pore sizes, as estimated from the positron annihilation, ranged from 0.2 to 0.6 nm for the dry membranes. Solubilities of methanol in different composite membranes were estimated from the Flory-Huggins theory. The interaction parameter was obtained from the surface properties measured by the contact angle goniometry in conjunction with the acid-base theory of polar surface interactions. For the membranes examined, the increase in the "wet" pore volume due to membrane swelling correlates almost linearly with the solubility of methanol in these membranes. Indeed, the observations are found to be consistent with the lowering of the equilibrium vapor pressure on the basis of the Kelvin equation. Thus, a higher solubility or selectivity of a membrane also implies stronger permeant-membrane interactions and a greater retention of the permeant by the membrane, thus decreasing its evaporative flux. This observation has important implications for the interpretation of existing experiments and in the separation of liquid mixtures by pervaporation.

Journal Article↗

PubMed2004

Polymer patterns in evaporating droplets on dissolving substrates.

Self-organized polymer patterns resulting from the evaporation of an organic solvent drop on a soluble layer of polymer are investigated. The patterns can be modulated by changing the rate of evaporation and also the rate of substrate dissolution controlled by its solubility. Both of these affect the contact zone motion and its instabilities, leading to spatially variable rates of substrate etching and redeposition that result from a complex interplay of several factors such as Rayleigh-Benard cells, thermocapillary flow, solutal Marangoni flow, flow due to differential evaporation, osmotic-pressure-induced flow, and contact-line pinning-depinning events. The most complex novel pattern, observed at relatively low rates of evaporation, medium solubility, and without macroscopic contact-line stick-slip, consists of a regularly undulating ring made up of a bundle of parallel spaghetti-like threads or striations and radially oriented fingerlike ridges. Increased rate of evaporation obliterates the polymer threads, producing more densely packed fingers and widely separated multiple rings due to a frequent macroscopic pinning-depinning of the contact line. Near-equilibrium conditions such as slow evaporation or increased solubility of the substrate engender a wider and less undulating single ring.

Journal Article↗

PubMed2004

Instability, dynamics, and morphology of thin slipping films.

Based on the linear stability and nonlinear simulations, we show that the surface instability, dynamics, and morphology of supported thin liquid films are profoundly altered by the presence of slippage on the substrate. A general dispersion equation for flow in slipping thin films is derived and simplified to identify three different regimes of slippage (weak, moderate, and strong) and obtain the length and time scales of instability in them. For illustration, the ubiquitous van der Waals interactions have been employed. Different regimes of slip-flow can be predicted based on a nondimensional parameter, xi, which is a function of slip length, film thickness, intermolecular potential, and interfacial tension. Two distinct transitions from weak to moderate slip and from moderate to strong slip occur at xiT1 approximately 0.01 and xiT2 approximately 500, respectively. More specifically, a decrease in film thickness causes transitions from weak to moderate to strong slip regime. Even a weak slippage causes faster breakup of a thin film, whereas slippage beyond a transition value (slip length, bT1) increases the length scale of instability and reduces the number density of holes compared to the nonslipping case. Strong slippage produces holes faster, and the holes are fewer in number and have less developed rims. The exponents for the length scale (lambdam infinity h0n; h0 is film thickness) and time scale of instability (tr infinity h0m) change nonmonotonically with slippage (for nonretarded van der Waals instability, n E (1.25, 2), m E (3, 6)). Retardation in van der Waals potential increases the exponents (n E (1.5, 2.5), m E (5, 8)). The initial stage of evolution of a slipping film, simulated based on nonlinear equations, follows the length scale and time scale of instability, close to the prediction of linear analysis. It is hoped that the present analysis will help in better interpretation of thin film experiments, in estimation of slippage, and in the determination of intermolecular forces from the length and time scales of the instability.

Computer Simulation↗

PubMed2003

Thermodynamics of critical strange nonchaotic attractors.

The thermodynamic formalism is applied to dynamical attractors which have fractal geometry and on which all Lyapunov exponents are exactly zero. Such critical strange nonchaotic attractors (SNAs) which arise, for example, in the Harper system exhibit a static phase transition in the free energy. The Tsallis nonextensive entropy which is known to characterize the thermodynamics of systems with leading Lyapunov exponent zero is found to be subadditive for the critical states. These properties are shared by other quasiperiodic systems with critical SNAs.

Journal Article↗

PubMed2003

Spontaneous surface roughening induced by surface interactions between two compressible elastic films.

The surfaces of soft thin elastic films bonded to two rigid substrates become spontaneously rough due to the attractive intersurface interactions when the intersurface distance declines sufficiently to produce a critical force. The effects of compressibility on the conditions for surface roughening and its length scale are investigated. For highly compressible films (nu less than 0.25), surface roughening is not possible. The critical force required for the onset of instability and its wave number both decline with increased compressibility. The wavelength of the instability is influenced much more by the properties of the more compliant film [compliance equals (1-2nu)h/2mu(1-nu)]. There is an abrupt change in the wavelength as the compliances of the two films become nearly equal.

Journal Article↗

PubMed2002

Instability of thin liquid films by density variations: a new mechanism that mimics spinodal dewetting.

Based on the linear stability analysis and nonlinear simulations, conditions are established under which instability and dewetting of a thin liquid film can be engendered solely by the density variations (for example, due to confinement, layering, defects, and restructuring) related to changes in the local film thickness. An increase in the density with the increasing film thickness can stabilize a thermodynamically unstable film, and, equally interesting, a decrease in the density with increasing film thickness can render a thermodynamically stable film unstable. Morphological characteristics of this novel density variation induced instability closely resemble the well-known spinodal dewetting.

Journal Article↗

PubMed2002

Spatiotemporal intermittency and scaling laws in inhomogeneous coupled map lattices.

We study the phenomenon of intermittency in an inhomogeneous lattice of coupled maps where the inhomogeneity appears in the form of different values of the map parameter at adjacent sites. This system exhibits spatiotemporal intermittency as well as purely spatial intermittency accompanied by temporal periodicity in different regions of the parameter space. Both types of intermittency appear as a result of bifurcations of codimension two in such systems. We identify the types of bifurcations that are seen. The intermittency near the bifurcation points and lines is associated with power-law distributions for the laminar lengths. The scaling laws for the laminar length distributions are obtained. Two distinct types of scaling behavior characterized by power laws with exponents that fall in two distinct ranges can be seen in the neighborhood of codimension-two bifurcation points. Additionally we find two crossover exponents.

Journal Article↗