Swelling, Diffusion, Hydrophilicity

Hydrogels. Controlled swelling of hydrophilic polymers, derived from the glossy/mbbery properties of polymers, is used to control the rate of dmg release from matrices. In the mbbery state, accompHshed by lowering the polymer s glass-transition temperature to an appropriate level, the dispersed dmg diffuses as the polymer swells in the presence of water. 

Drug delivery from LLC phases of oligo(ethylene oxide)-alkyl ether (i.e., (E0) -0-alkyl) surfactants have also been explored but to a much lesser extent than GMO. For example, the L, Qn, and Hu phases of commercial Brij-96 surfactant (i.e., (EO)io-O-oleyl) (Fig. 18) formed with water and other additives, have been explored for release of ephedrine hydrochloride, tenoxi-cam [145], and topical dermal delivery of benzocaine [146]. Work in this area has found that the amount of water swelling the hydrophilic domains of the LLC phase increases drug diffusion and release [145]. In addition to this work, the L phase of the (EO)2i-0-stearyl/oil/water system has been explored for dermal delivery of itraconazole [147] and the L and Hi phases of the (E0)7-0-Ci3 i5 (i.e., Symperonic A7)/water system have been explored for the release of the model drug chlorhexidine diacetate [148]. 

Ethylene glycol facilitates coalescent evaporation because it swells the hydrophilic network, thereby creating a larger pathway for diffusion. The rate of initial water evaporation is unaffected by coalescing solvents, but they may retard final evaporation. The more polar the solvent, the faster it will evaporate. The use of a water soluble solvent enables water evaporation to be faster than the rate of diffusion during the final stages. In the absence of solvents, or in the presence of water insoluble solvents, water evaporation is diffusion controlled. 

Adsorption and diffusion phenomena at or within polymer systems were investigated by surface sensitive ATR-FTIR spectroscopy. For a systematic description, a study was made of (1) the competitive adsorption and desorption behaviour of proteins on polymer surfaces, (2) swelling of hydrophilic polymers by water molecules, which can be accompanied by conformational changes, and (3) induced orientational changes of hydrophobically modified polypeptides by apolar solvents. 10 refs. 

When the reaction times for Step 1 are 5 min or longer, the samples severely crack, curl, or dissolve. These results suggest that substantial reaction is occurring in the bulk of the polymer. Significant hydrophilization can occur with reaction times as short as 5 s with RTD concentrations of 0.2-0.5 M. However, 0.002-0.02 M solutions of MeTD or PhTD do not allow sufficient reaction rates for surface hydrophilization at the shorter reaction times. Thus, diffusion of MeTD and PhTD into the polymer must occur readily from the acetonitrile solutions. Acetonitrile was used because it does not swell or dissolve the polymer or RTD-polymer adduct, and the RTDs are soluble and stable in it. This solvent is quite polar (dielectric constant, 38) (25), and this is probably a major factor in the partitioning of the relatively nonpolar RTDs between the polydiene film and the solvent. As noted below, more polar RTDs show less tendency to diffuse into the polymer. 

Hydrophilic polymers (Table 5) provide a matrix which is comparable to an aqueous environment. Ions can diffuse quite freely, but the possible water uptake (10-1000%) can cause significant swelling of the polymer. Swelling of the matrix affects the optical properties of the sensors and, consequently, the signal changes. Immobilization of the indicator chemistry usually is achieved via covalent bonding to the polymer. 

We include certain excipients in a formulation specifically because they interact with the physiological fluids and the bodily functions in a certain way. For example, as discussed above, we include disintegrants in immediate release tablet and capsule formulations, because we know that when they encounter the aqueous environment of the stomach, they will cause the tablet or capsule to disintegrate and thereby aid dissolution of the API. Another example is the general case of hydrophilic colloid matrices used as prolonged release drug delivery systems. We know that when these materials contact the aqueous environment of the GIT they swell and create a diffusion barrier that slows the rate of dissolution of the dissolved drug. 

An additional consideration in the cleaning of XAD resins is their flexible structure. The resin beads swell on contact with hydrophilic or polar solvents such as methanol (29). The nonpolar surface of the resin is repelled by polar solvents and attracted by nonpolar solvents. This effect causes the internal pore diameters to increase or decrease, respectively. The cleaning solvent or mixture of solvents must be polar to keep the internal pores open so that the contaminants will diffuse faster from the interior of the beads to the bulk solvent. However, the resin contaminants themselves are nonpolar, as shown in Table IV, and are not very soluble in polar solvents. The choice of an optimum resincleaning solvent should therefore be a compromise between diffusion and solubility. In addition, the solvent used after the water backwash must be miscible with water to remove the water from the resin pores. 

Soluble matrix systems. The third matrix system is based on hydrophilic polymers that are soluble in water. For these types of matrix systems, water-soluble hydrophilic polymers are mixed with drugs and other excipients and compressed into tablets. On contact with aqueous solutions, water will penetrate toward the inside of the matrix, converting the hydrated polymer from a glassy state (or crystalline phase) to a rubbery state. The hydrated layer will swell and form a gel, and the drug in the gel layer will dissolve and diffuse out of the matrix. At the same time, the polymer matrix also will dissolve by slow disentanglement of the polymer chains. This occurs only for un-cross-linked hydrophilic polymer matrices. In these systems, as shown in Fig. 5.3, three fronts are formed during dissolution9-11 ... 

It seems reasonable that molecules of a surfactant may diffuse from the spray droplet into the cuticle of leaves perhaps via imperfections and cracks and then align themselves in monolayers with their nonpolar ends oriented in the cutin and wax. The polar ends will thus also form a layer whose size depends on the length of the hydrophilic chain of the surfactant molecule. These layers or hydrophilic channels will presumably attract water, causing swelling of the cuticle, and thus channels or pores are formed along which herbicide molecules can diffuse according to their various chemical properties (solubility, residual chemical charge, polar properties, etc.). 

Soluble drugs are considered to be released by diffusion through the matrix and poorly soluble drugs are released by erosion of the matrix. Moreover, it is considered that factors affecting swelling and erosion of these polymers may account for differences between in vitro dissolution results and subsequent in vivo performance when hydrophilic matrix tablets are compared [15]. 

The mechanism of action of disintegrating agents has been the subject of some debate. Some substances such as starch swell when they come into contact with water, and disruption of the tablet structure has been attributed to this. However, other effective disintegrants do not swell in this way, and are believed to act by providing a network of hydrophilic pathways inside the tablet through which water can diffuse. Irrespective of the precise mechanism of disintegration, it is clear that water uptake into the tablet must be the first step in the disintegration process. ... 

As a consequence of its hydrophilicity, wood tissue will seek to maintain, through either gain or loss of moisture, an equilibrium moisture content with the surrounding atmosphere. If the wood takes on water, the cell walls proceed to swell until the cell walls become water-saturated. The latter moisture content is called the wood s fiber saturation point. In contrast, loss of wood water (below the fiber saturation point), due to diffusion and evaporation, results in wood shrinkage. 

The extension of these equation to hydrophilic matrices is difficult because the conditions in a hydrophilic matrix change with time as water penetrates into it. If the polymer does not dissolve but simply swells and if the drug has not completely dissolved in the incoming solvent, diffusion of dmg commences from a saturated solution through the gel layer, and... 

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