Design and Evaluation of Matrix Diffusion Controlled Transdermal Patches of Diltiazem Hydrochloride

Se desarrolló un sistema matricial de tipo dispersivo para la administración transdérmica de clorhidrato de Diltiazem usando diferentes proporciones de colofonia con Eudragit RL PM y polivinil pirrolidona. El parche preparado con colofonia y polivinil pirrolidona no era transparente y muestra una distribución irregular de polivinil pirrolidona, lo que puede ser debido al carácter hidrófi lo de ésta. Se investigó el efecto de los polímeros sobre las propiedades tecnológicas; es decir, la liberación del fármaco, la velocidad de transmisión del vapor de agua, la pérdida porcentual de humedad y el grosor. El parche con colofonia: Eudragit RL PM (6:4) dio como resultado una liberación de 2651 mcg en 24 horas. Con el objeto de mejorar la liberación, se incluyeron distintas proporciones de alcanfor en la formulación. El parche con colofonia: Eudragit RL PM (6:4) y un 5% p/v de alcanfor dio como resultado una liberación constante del fármaco a lo largo de un período de 24 horas. La formulación F8 resultó ser la más satisfactoria en lo que a las propiedades tecnológicas se refi ere. Se llevaron a cabo estudios posteriores de permeación e irritación de la piel en ratas y conejos respectivamente. Por lo tanto, se puede concluir que con el parche de colofonia: Eudragit RL PM en proporción 6:4 con un 5% p/v de alcanfor, se alcanzan los objetivos deseables en sistemas de administración transdérmica de fármacos tales como anular el efecto de primer paso, una amplia liberación y una frecuencia de administración reducida.A matrix dispersion type transdermal drug delivery system of Diltiazem Hydrochloride was developed using different ratios of rosin with Eudragit RL PM and polyvinyl pyrrolidone. The patch prepared by the combination of rosin and polyvinyl pyrrolidone was not transparent one, and shows an uneven distribution of polyvinyl pyrrolidone, which may be due to the hydrophilic nature of polyvinyl pyrrolidone. The effect of the polymers on the technological properties, i.e., drug release, water vapor transmission rate, percentage moisture loss and thickness were investigated. The patch containing rosin: Eudragit RL PM (6:4) showed a release of 2651 mcg in 24 h. In order to improve the release various proportions of camphor was included in the formulation. The patch containing rosin: Eudragit RL PM (6:4) with 5% w/v of camphor showed a sustained release of the drug extending over a period of 24 h. Formulation F8 emerged as the most satisfactory formulation as far as the technological properties were concerned. Further skin permeation and skin irritation studies were carried out on rat skin and rabbit respectively. Therefore it can be concluded that the patch containing rosin: Eudragit RL PM in the ratio 6:4 with 5%w/v of camphor achieved the desired objectives of transdermal drug delivery systems, such as overcoming of fi rst pass effect, extended release and reduced frequency of administration

Formulation and evaluation of oral sustained release of Diltiazem Hydrochloride using rosin as matrix forming material

Rosin, a natural resin, was used as a hydrophobic matrix material for the controlled release, using diltiazem HCl as model drug. Matrix tablets were prepared by direct compression method using rosin as matrix forming material in different proportions and with different diluent combinations. The tablets prepared were flat faced, retained their shape throughout. The method of preparation of matrix system and its concentration were found to have pronounced effect on the release of diltiazem HCl. The release was found to follow both the first order kinetics and fickian diffusion. The drug delivery was analyzed using the paddle method according to USP XXIII. All the studies were done in phosphate buffer pH 7.4. The matrix tablets were evaluated for its thickness, hardness, friability, weight variation, drug content and invitro release studies. The results suggest that the rosin is useful in developing sustained release matrix tablets, prolong release of water soluble drug for up to 24h. Rosin thus promises considerable utility in the development of oral sustained release drug delivery systems

Competition of Mesoscales and Crossover to Tricriticality in Polymer Solutions

We show that the approach to asymptotic fluctuation-induced critical behavior in polymer solutions is governed by a competition between a correlation length diverging at the critical point and an additional mesoscopic length-scale, the radius of gyration. Accurate light-scattering experiments on polystyrene solutions in cyclohexane with polymer molecular weights ranging from 200,000 up to 11.4 million clearly demonstrate a crossover between two universal regimes: a regime with Ising asymptotic critical behavior, where the correlation length prevails, and a regime with tricritical theta-point behavior determined by a mesoscopic polymer-chain length.Comment: 4 pages in RevTeX with 4 figure

Towards a quantitative phase-field model of two-phase solidification

We construct a diffuse-interface model of two-phase solidification that quantitatively reproduces the classic free boundary problem on solid-liquid interfaces in the thin-interface limit. Convergence tests and comparisons with boundary integral simulations of eutectic growth show good accuracy for steady-state lamellae, but the results for limit cycles depend on the interface thickness through the trijunction behavior. This raises the fundamental issue of diffuse multiple-junction dynamics.Comment: 4 pages, 2 figures. Better final discussion. 1 reference adde

The resistive state in a superconducting wire: Bifurcation from the normal state

We study formally and rigorously the bifurcation to steady and time-periodic states in a model for a thin superconducting wire in the presence of an imposed current. Exploiting the PT-symmetry of the equations at both the linearized and nonlinear levels, and taking advantage of the collision of real eigenvalues leading to complex spectrum, we obtain explicit asymptotic formulas for the stationary solutions, for the amplitude and period of the bifurcating periodic solutions and for the location of their zeros or "phase slip centers" as they are known in the physics literature. In so doing, we construct a center manifold for the flow and give a complete description of the associated finite-dimensional dynamics

Banning the bulb: institutional evolution and the phased ban of incandescent lighting in Germany

Much academic attention has been directed at analysing energy efficiency investments through the lens of ‘behavioural failure’. These studies have challenged the neoclassical framing of regulation which emphasises the efficiency benefits of price based policy, underpinned by the notion of rational individual self-mastery. The increasing use of a regulatory ban on electric lamps in many countries is one of the most recent and high profile flash points in this dialectic of ‘freedom-versus-the-state’ in the public policy discourse. This paper interrogates this debate through a study of electric lamp diffusion in Germany. It is argued that neoclassical theory and equilibrium analysis is inadequate as a tool for policy analysis as it takes the formation of market institutions, such as existing regulations, for granted. Further still, it may be prone to encourage idealistic debates around such grand narratives which may in practice simply serve those who benefit most from the status quo. Instead we argue for an evolutionary approach which we suggest offers a more pragmatic framing tool which focuses on the formation of market institutions in light of shifting social norms and political goals—in our case, progress towards energy efficiency and environmental goals

Relativistic description of electron scattering on the deuteron

Within a quasipotential framework a relativistic analysis is presented of the deuteron current. Assuming that the singularities from the nucleon propagators are important, a so-called equal time approximation of the current is constructed. This is applied to both elastic and inelastic electron scattering. As dynamical model the relativistic one boson exchange model is used. Reasonable agreement is found with a previous relativistic calculation of the elastic electromagnetic form factors of the deuteron. For the unpolarized inelastic electron scattering effects of final state interactions and relativistic corrections to the structure functions are considered in the impulse approximation. Two specific kinematic situations are studied as examples.Comment: (19 pages in revtex + 15 figures not included, available upon request.) report THU-93-10

Generation of defects and disorder from deeply quenching a liquid to form a solid

We show how deeply quenching a liquid to temperatures where it is linearly unstable and the crystal is the equilibrium phase often produces crystalline structures with defects and disorder. As the solid phase advances into the liquid phase, the modulations in the density distribution created behind the advancing solidification front do not necessarily have a wavelength that is the same as the equilibrium crystal lattice spacing. This is because in a deep enough quench the front propagation is governed by linear processes, but the crystal lattice spacing is determined by nonlinear terms. The wavelength mismatch can result in significant disorder behind the front that may or may not persist in the latter stage dynamics. We support these observations by presenting results from dynamical density functional theory calculations for simple one- and two-component two-dimensional systems of soft core particles.Comment: 25 pages, 11 figure

Red Queen Coevolution on Fitness Landscapes

Species do not merely evolve, they also coevolve with other organisms. Coevolution is a major force driving interacting species to continuously evolve ex- ploring their fitness landscapes. Coevolution involves the coupling of species fit- ness landscapes, linking species genetic changes with their inter-specific ecological interactions. Here we first introduce the Red Queen hypothesis of evolution com- menting on some theoretical aspects and empirical evidences. As an introduction to the fitness landscape concept, we review key issues on evolution on simple and rugged fitness landscapes. Then we present key modeling examples of coevolution on different fitness landscapes at different scales, from RNA viruses to complex ecosystems and macroevolution.Comment: 40 pages, 12 figures. To appear in "Recent Advances in the Theory and Application of Fitness Landscapes" (H. Richter and A. Engelbrecht, eds.). Springer Series in Emergence, Complexity, and Computation, 201