Modification permeation

The chemical modification of poly (2,6-dimethyl-l,4-phenylene oxide) (PPO) by several polymer analogous reactions is presented. The chemical modification was accomplished by the electrophilic substitution reactions such as bromination, sulfonylation and acylation. The permeability to gases of the PPO and of the resulting modified polymers is discussed. Very good permeation properties to gases, better than for PPO were obtained for the modified structures. The thermal behavior of the substituted polymers resembled more or less the properties of the parent polymer while their solution behavior exhibited considerable differences. 

In our research, three chemical modification approaches were investigated bromination, sulfonylation, and acylation on the aromatic ring. The specific objective of this paper is to present the chemical modification on the PPO backbone by a variety of electrophilic substitution reactions and to examine the features that distinguish modified PPO from unmodified PPO with respect to gas permeation properties, polymer solubility and thermal behavior. 

Chemical modifications of PPO by electrophilic substitution of the aromatic backbone provided a variety of new structures with improved gas permeation characteristics. It was found that the substitution degree, main chain rigidity, the bulkiness and flexibility of the side chains and the polarity of the side chains are major parameters controlling the gas permeation properties of the polymer membrane. The broad range of solvents available for the modified structures enhances the possibility of facile preparation of PPO based membrane systems for use in gas separations. 

The ex vivo methods lend themselves easily for the performance of mechanistic investigations. In order to optimize selection of drug candidates prior to further clinical development, it is important to decipher the contributive roles of permeation, metabolism, efflux, and toxicity. This will then make it possible to properly channel the optimization process, for instance, by permeation enhancement, mucoadhesion, modification of the physicochemical characteristics of the drug, or even change in the route of administration in case the drug and/or formulation turns out to be too toxic. Regarding permeability studies, it is possible not only to quantify passive diffusion but also to identify and characterize (compound)-specific carrier-mediated transport routes. These tools have been used to identify and characterize the relative contribution of... 

The major strategies to enhance transmucosal peptide and other drug absorption include (a) coadministration with protease inhibitors, (b) the use of membrane permeation enhancers, (c) coadministration with a combination of absorption enhancers and protease inhibitors, (d) modification of peptide structure to improve metabolic stability or membrane permeation, and (e) use of nano- or microparticles [27], Some of these strategies have been investigated using the in situ rat model. 

In a second approach, Sugano et al. [138] tried to consider paracellular transport in addition to transcellular permeation. The prediction of the paracellular transport potential was based on size and charge parameters together with artificial membrane permeability in relation to known human absorption values. Other groups have focused on the paracellular route by modification of the assay [26],... 

Yazawa, T., H. Nakamichi, H. Tanaka and K. Eguchi. 1988. Permeation of liquid through a porous glass membrane with surface modification. Nippon Seramikkusu Kyokai Gakujutsu Ronbunshi 96(1) 18-23. 

Although descriptions of chemical change are permeated with the terms and language of molecular theory, the concepts of classic thermodynamics are independent of molecular theory thus, these concepts do not require modification as our knowledge of molecular structure changes. This feature is an advantage in a formal sense, but it is also a distinct limitation because we cannot obtain information at a molecular level from classic thermodynamics. 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

The approach applies to repeated observations pertinent to each treatment, or to observations in two-dimensional arrays, if one factor (which could serve as the block in a two-factor analysis) is considered as a replicate entity. The idea is illustrated in the case of permeation fluxes through a membrane [15] with pertinent calculations given in Table 3. If the effect of the k = 6 salts is considered as a replicate (random) phenomenon, and the observed and calculated values (N= 2) are ranked according to the flux observations, the probability computed by an appropriate modification of Eq.(3) as... 

Membrane permeability is one of the most important determinants of pharmacokinetics, not only for oral absorption, but also for renal re-absorption, biliary excretion, skin permeation, distribution to a specific organ and so on. In addition, modification of membrane permeability by formulation is rarely successful. Therefore, membrane permeability should be optimized during the structure optimization process in drug discovery. In this chapter, we give an overview of the physiology and chemistry of the membranes, in vitro permeability models and in silica predictions. This chapter focuses on progress in recent years in intestinal and blood-brain barrier (BBB) membrane permeation. There are a number of useful reviews summarizing earlier work [1-5]. 

Seeded polymerization using a slight amount of monomer leads to the surface modification without changing particle size. The resulting particles are a kind of core-shell particles or, more exactly, core-skin particles (Fig. 12.2.4C). Seeded polymerization of sugar-units-containing styrene derivative on polystyrene seed particle was carried out to obtain latex particles covered with sugar units (17). A necessary condition for this is that the monomer is more hydrophilic than the seed polymer. If not, the monomer permeates into the seed particle and only a small fraction remains on the... 

As described above, the modification of the polyamide membrane with pendant polar groups effectively improved their permeation characteristics. 

Modification of the sensor structure. The above amperometric sensor has a rather complicated construction, because the sample gas (H2 + air) is separated from the reference air. So, we tried to simplify the sensor structure as shown in Figure 9. As proton conductor we used a thin antimonic acid membrane (mixed with Teflon powder) of 0.2 mm thickness. This membrane is thin and porous enough to allow a part of the sample gas to permeate. On the other hand, the counter Pt electrode was covered with Teflon and Epoxy resin in order to avoid a direct contact with the sample gas. 

The traditional methods for evaluation of the delivery and metabolism of exogenous materials in skin involve the use of diffusion cells and/or tape stripping followed by HPLC and mass spectrometry. These methods involve modification of the skin, provide no spatial information, and may alter skin transport properties. In this section, both the permeation and metabolism of a-TAc are monitored inside skin with confocal Raman microscopy. 

PE, being a commodity polymer, is used in its different physical forms viz. fibres, sheets, membranes, moulds with different backbone chemical configurations (LPE, LLDPE, LDPE, HDPE, UHMWPE, UHSPE etc). Each of these forms of PE requires surface modification at some stage of application. The surfaces of PE fibres are often modified to make them compatible in the composites, whereas PE sheets/tapes are modified to achieve adhesion. Moulds are frequently surface-modified for probability and membranes for selective permeation. In the same way, different chemical configurations of PE, by the virtue of their properties, are used for different applications after surface modification. 

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