Modeling the drug release from hydrogel-based matrices

In this work the behavior of hydrogel-based matrices, the most widespread systems for oral controlled release of pharmaceuticals, has been mathematically described. In addition, the calculations of the model have been validated against a rich set of experimental data obtained working with tablets made of hydroxypropyl methylcellulose (a hydrogel) and theophylline (a model drug). The model takes into account water uptake, hydrogel swelling, drug release, and polymer erosion. The model was obtained as an improvement of a previous code, describing the diffusion in concentrated systems, and obtaining the erosion front (which is a moving boundary) from the polymer mass balance (in this way, the number of fitting parameters was also reduced by one). The proposed model was found able to describe all the observed phenomena, and then it can be considered a tool with predictive capabilities, useful in design and testing of new dosage systems based on hydrogels

Influence of a knot on the strength of a polymer strand

Many experiments have been done to determine the relative strength of different knots, and these show that the break in a knotted rope almost invariably occurs at a point just outside the `entrance' to the knot. The influence of knots on the properties of polymers has become of great interest, in part because of their effect on mechanical properties. Knot theory applied to the topology of macromolecules indicates that the simple trefoil or `overhand' knot is likely to be present with high probability in any long polymer strand. Fragments of DNA have been observed to contain such knots in experiments and computer simulations. Here we use {\it ab initio} computational methods to investigate the effect of a trefoil knot on the breaking strength of a polymer strand. We find that the knot weakens the strand significantly, and that, like a knotted rope, it breaks under tension at the entrance to the knot.Comment: 3 pages, 4 figure

Parallel Excluded Volume Tempering for Polymer Melts

We have developed a technique to accelerate the acquisition of effectively uncorrelated configurations for off-lattice models of dense polymer melts which makes use of both parallel tempering and large scale Monte Carlo moves. The method is based upon simulating a set of systems in parallel, each of which has a slightly different repulsive core potential, such that a thermodynamic path from full excluded volume to an ideal gas of random walks is generated. While each system is run with standard stochastic dynamics, resulting in an NVT ensemble, we implement the parallel tempering through stochastic swaps between the configurations of adjacent potentials, and the large scale Monte Carlo moves through attempted pivot and translation moves which reach a realistic acceptance probability as the limit of the ideal gas of random walks is approached. Compared to pure stochastic dynamics, this results in an increased efficiency even for a system of chains as short as $N = 60$ monomers, however at this chain length the large scale Monte Carlo moves were ineffective. For even longer chains the speedup becomes substantial, as observed from preliminary data for $N = 200$

The electric double layer has a life of its own

Using molecular dynamics simulations with recently developed importance sampling methods, we show that the differential capacitance of a model ionic liquid based double-layer capacitor exhibits an anomalous dependence on the applied electrical potential. Such behavior is qualitatively incompatible with standard mean-field theories of the electrical double layer, but is consistent with observations made in experiment. The anomalous response results from structural changes induced in the interfacial region of the ionic liquid as it develops a charge density to screen the charge induced on the electrode surface. These structural changes are strongly influenced by the out-of-plane layering of the electrolyte and are multifaceted, including an abrupt local ordering of the ions adsorbed in the plane of the electrode surface, reorientation of molecular ions, and the spontaneous exchange of ions between different layers of the electrolyte close to the electrode surface. The local ordering exhibits signatures of a first-order phase transition, which would indicate a singular charge-density transition in a macroscopic limit

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses

The stability inequality for Ricci-flat cones

In this article, we thoroughly investigate the stability inequality for Ricci-flat cones. Perhaps most importantly, we prove that the Ricci-flat cone over CP^2 is stable, showing that the first stable non-flat Ricci-flat cone occurs in the smallest possible dimension. On the other hand, we prove that many other examples of Ricci-flat cones over 4-manifolds are unstable, and that Ricci-flat cones over products of Einstein manifolds and over Kähler-Einstein manifolds with h^{1,1}>1 are unstable in dimension less than 10. As results of independent interest, our computations indicate that the Page metric and the Chen-LeBrun-Weber metric are unstable Ricci shrinkers. As a final bonus, we give plenty of motivations, and partly confirm a conjecture of Tom Ilmanen relating the lambda-functional, the positive mass theorem and the nonuniqueness of Ricci flow with conical initial data

Mathematical models for estimating effective diffusion parameters of spherical drug delivery devices

Mathematical modeling of drug delivery is of increasing academic and industrial importance in manyaspects. In this paper, we propose an optimization approach for the estimation of the parameters characterizing the diffusion process of a drug from a spherical porous polymer device to an external finite volume. The approach is based on a nonlinear least-squares method and a novel mathematical model which takes into consideration both boundary layer effect and initial burst phenomenon. Ananalytical solution to the model is derived and a formula for the ratio of the mass released in a given time interval and the total mass released in infinite time is also obtained. The approach has been tested using experimental data of the diffusion of prednisolone 21-hemisuccinate sodium saltfrom spherical devices made of porous poly(2-hydroxyethyl methacrylate) hydrogels. The effectiveness and accuracy of the method are well demonstrated by the numerical results. The model was used to determine the diffusion parameters including the effective diffusion coefficient of the drug from a series of devices that vary in both the porous structure and the drug loading levels. The computed diffusion parameters are discussed in relation to the physical properties of the devices

Cyclodextrin/cellulose hydrogel with gallic acid to prevent wound infection

Cyclodextrin-based hydrogels have been described as suitable for the controlled-release of bioactive molecules to be used as wound dressing. These materials have major advantages, since they gather the hydrogel properties (high degree of swelling and easy manipulation) and the encapsulation ability of cyclodextrins. β-cyclodextrin (β) or hydroxypropyl-β-cyclodextrin (HPβ) was cross-linked (1,4-butanediol diglycidyl ether) with hydroxypropyl methylcellulose under mild conditions. The hydrogels were chemically characterized by swelling degree, FTIR, DSC and contact angle. The gallic acid loading and release was also analysed, as well the antibacterial activity and cytotoxicity of the polymeric networks. The hydrogels obtained were firm and transparent, with good swelling ability. The gel-HPβ had a surface more hydrophilic when compared with the gel-β. Nevertheless, both hydrogels were capable to incorporate gallic acid and sustain the release for 48 h. The antibacterial activity of gallic acid was maintained after its adsorption within the polymeric matrix, as well as, gallic acid effect on fibroblast proliferation. Therefore, gel-β and gel-HPβ conjugated with gallic acid were shown to be a viable option for antibacterial wound dressing.The authors thank the FCT Strategic Projects PEst-OE/EQB/LA0023/2013, PEst-C/CTM/UI0264/2011, the Project "BioHealth-Biotechnology and Bioengineering approaches to improve health quality'', Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional doNorte (ON.2-ONovoNorte), QREN, FEDER, and E. Pinho grant (SFRH/BD/62665/2009)

Bioadhesive Controlled Metronidazole Release Matrix Based on Chitosan and Xanthan Gum

Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole Cmax and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole