Permeability characteristics

The permeability characteristics of the bis-phenol A polyearbonates are shown in Table 20.7. 

While it would be difficult to enumerate all of the efforts in the area of implants where plastics are involved, some of the significant ones are (1) the implanted pacemaker, (2) the surgical prosthesis devices to replace lost limbs, (3) the use of plastic tubing to support damaged blood vessels, and (4) the work with the portable artificial kidney. The kidney application illustrates an area where more than the mechanical characteristics of the plastics are used. The kidney machine consists of large areas of a semi-permeable membrane, a cellulosic material in some machines, where the kidney toxins are removed from the body fluids by dialysis based on the semi-permeable characteristics of the plastic membrane. A number of other plastics are continually under study for use in this area, but the basic unit is a device to circulate the body fluid through the dialysis device to separate toxic substances from the blood. The mechanical aspects of the problem are minor but do involve supports for the large amount of membrane required. 

JS Fordtran, FC Rector, Jr., MF Ewton, N Soter, J Kinney. Permeability characteristics of the human small intestine. J Clin Invest 44 1935-1944, 1965. 

A good deal of attention recently has been directed towards the use of derivatives of cyclodextrin for the solubilization and stabilization of pharmaceuticals [124 126]. One cautionary note—complexation may adversely affect the dissolution an/or permeability characteristics of the drug, thereby possibly decreasing drug bioavailability. 

Natural drainage materials should be tested to ensure that they will not dissolve in the leachate or form a precipitant that might clog the system. ASTM D243442 will evaluate the ability of the materials to retain permeability characteristics, while ASTM D188343 tests for bearing ratio, or the ability of the material to support the waste unit. 

Kim DC, PS Burton, RT Borchardt. (1993). A correlation between the permeability characteristics of a series of peptides using an in vitro cell culture model (Caco-2) and those using an in situ perfused rat ileum model of the intestinal mucosa. Pharm Res 10 1710-1714. 

There is growing evidence implicating Na+-dependent solute transporters and intracellular as well as extracellular Ca2+ in the physiological regulation of the paracellular pathway [81,203,204], Such modulation of paracellular permeability is especially important for drugs such as peptides and oligonucleotides that exhibit poor permeability characteristics across both the cornea and the conjunctiva [150,152,154,155], In addition, ion transporters such as Cl and Ca2+ channels have been implicated in macromolecular transport (see Sections IV.B.2 and IV.B.4). In the following discussion, some key ion transport processes and their possible roles in solute transport across epithelial tissues are summarized. 

W Rubas, N Jezyk, GM Grass. Comparison of the permeability characteristics of a human colonic epithelial (Caco-2) cell line to colon of rabbit, monkey, and dog intestine and human drug absorption. Pharm Res 10 113-118, 1993. 

Hydration can be an important factor in diffusion and mass transport phenomena in pharmaceutical systems. It may alter the apparent solubility or dissolution rate of the drug, the hydrodynamic radii of permeants, the physicochemical state of the polymeric membrane through which the permeant is moving, or the skin permeability characteristics in transdermal applications. 

Duizer, E., Penninks, A. H., Stenhuis, W. H., Groten, J. P., Comparison of permeability characteristics of the human colonic Caco-2 and rat small intestinal IEC-18 cell lines, J. Controlled Release 1997,... 

Based on their solubility and intestinal permeability characteristics, drugs have been classified into one of four categories according to the Biopharmaceutics Classification System (BCS) proposed by Amidon et al. [49]. 

Recently, we proposed an alternative process for encapsulating biomacromolecules within PE microcapsules. This approach involves using nanoporous particles as sacrificial templates for both enzyme immobilization and PE multilayer capsule formation (Figure 7.2, route (I)) [66,67]. Unlike previous LbL encapsulation strategies, this approach is not limited to species that undergo crystallization, and is not dependent upon adjustments in electrostatic interactions within PE microcapsules to alter shell permeability characteristics. The salient feature of this method is that it is applicable to a wide range of materials for encapsulation. 

Because the matrix has permeable characteristics, the ability of the molecules to diffuse will depend on the pore size of the permeable polymer and the available free space in the pores. Obviously, larger molecules would not be able to penetrate the matrix and complex with the NIR dye. As the amount of the dye-analyte complexes increase, the amount of free space into which other analytes can diffuse decreases. Therefore, a relation of the mobility with free space is defined as... 

Refinement and expansion of these steady-state mass balance approaches has led to the development of dynamic models which allow for estimation of the fraction absorbed as a function of time and can therefore be used to predict the rate of dmg absorption [37], These compartmental absorption and transit models (CAT) models have subsequently been used to predict pharmacokinetic profiles of drugs on the basis of in vitro dissolution and permeability characteristics and drug transit times in the intestine [38],... 

Thus, the apparent membrane permeability characteristics of hydrophilic compounds listed in Table 3.4 indicate that colonic epithelium is different from small intestinal epithelium in selectivity, or size or density distribution of the paracellular pathway. This is further complicated because of the possible involvement of unidentified carriers or channels for some compounds, as suggested for glycerol and D-xylose. However, the colon-to-SI ratios of the apparent membrane permeability are generally comparable with (or lower than) those calculated considering the morphological surface area, suggesting that such factors are not in favor for colonic absorption in most cases. Matching... 

Nicolazzo JA, Reed BL, Finnin BC (2003) The effect of various in vitro conditions on the permeability characteristics of the buccal mucosa. J Pharm Sci 92 2399-2410... 

Prabhu S, Ortega M, Ma C (2005) Novel lipid-based formulations enhancing the in vitro dissolution and permeability characteristics of a poorly water-soluble model drug, piroxicam. Int J Pharm 301 209-216. 

Mathias NR, Timoszyk J, Stetsko PI, Megill JR, Smith RL, Wall DA (2002) Permeability characteristics of calu-3 human bronchial epithelial cells In vitro-in vivo correlation to predict lung absorption in rats. J Drug Target 10(1) 31—40. 

Goskonda VR, Khan MA, Hutak CM, Reddy IK. Permeability characteristics of novel mydriatic agents using an in vitro cell culture model that utilizes SIRC rabbit comeal cells. J Pharm Sci 88 180-184 (1999). 

Solubility and permeability were measured by a high throughput solubility assay and parallel artificial membrane permeation assay (PAMPA), respectively [56], The assays categorized 14 out of 18 drugs based on the BCS consistent with their known solubility and permeability characteristics [56],... 

Partly due to the limited throughput of Caco-2 permeability measurements, the structure-activity evaluation of compounds tested in the hit-to-lead phase is done with minimal permeability information, at best. Given the importance of membrane permeability in drug absorption, early consideration of the permeability characteristics of hit compounds would enhance the drug-like quality, and ultimately the probability of success, of selected lead candidates. To incorporate permeability information into the hit-to-lead phase of the drug discovery process it is necessary that permeability measurements be made quickly and with small amounts of material. Thus, efforts have been made to automate and miniaturize the Caco-2 permeability assay. 

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