Permeation enhancers, examples

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

Ultrafiltration of heterogenous colloidal suspensions such as citrus juice is complex and many factors other than molecular weight contribute to fouling and permeation. For example, low MW aroma compounds were unevenly distributed in the permeate and retentate in UF in 500 kd MWCO system (10). The authors observed that the 500 kd MWCO UF removed all suspended solids, including pectin and PE. If PE is complexed to pectate in an inactive complex, then it is conceivable that release of PE from pectin with cations will enhance permeation in UF. At optimum salt concentration, less PE activation was observed at lower pH values than at higher pH (15). In juice systems, it is difficult to separate the effect of juice particulates on PE activity. Model studies with PE extracts allows UF in the absence of large or insoluble particulates and control of composition of the ultrafilter. In... 

Other Toxicity Concerns. Additional toxicity concerns include interference with normal metabolism and function of mucosal cells, for example, water absorption by these cells [80]. The unconjugated bile acids are known to block amino acid metabolism [81] and glucose transport [82]. There is a possibility of biotransformation of these enhancers to toxic or carcinogenic substances by hepatic monooxygenases [83]. Absorption of permeation enhancers into the systemic circulation can also cause toxicity, for example, azone [84] and hexamethylene lauramide [85] which are absorbed... 

Receptor-mediated transporters are excipients that serve as substrates to exploit specific receptors present on cell membranes. Examples of various receptors that have been explored for permeation enhancement include bile acids (45), vitamin Bi2 (46), amino acids (47), and folic acid (48). Most of the work in receptor-mediated transporters is conducted via the use of prodrugs. For example, a prodrug of acyclovir conjugated to bile acids was seen to have higher permeability as compared to the original drug, because of receptor-mediated transport of the prodrug via bile acid transporters (49). 

FIGURE 10.5 Some examples of surfactants used as permeation enhancers. 

Table 6.4 Examples of oral mucosal permeation enhancement.

The skin permeation of ACV (Zovirax cream) applied as a finite dose was promoted to a greater extent as the duration of brush treatment was extended (Fig. 5.2). A significant increase in ACV transport was observed following brush treatment (p < 0.05). The use of iontophoresis proved generally less effective than employing the rotating brush in enhancing permeation. For example the effect of 10-min anodal iontophoresis on the skin permeation of ACV proved to be comparable to that obtained after application of brush treatment at SOON m" for 10s (Table 5.2). The iontophoretic method in this study employed optimum conditions (electrode type, anode pFl of buffer, 7.4 current intensity. 

On the other hand, SEPA (2-n-nonyl-l,3-dioxolane) has been shown to be a more versatile penetration enhancer in terms of its ease of formulation, chemical stability and its ability to enhance the skin penetration of a wide variety of compounds of varying physicochemical characteristics. Permeants that have been evaluated include indomethacin, ibuprofen, minoxidil, acyclovir, caffeine, econazole, papaverine, progesterone and estradiol. The degree of skin penetration enhancement using SEPA is dependent on the physicochemical characteristics of the permeant. For example, following application of indomethacin in a simple ethanol-propylene glycol vehicle to human skin in vitro, cumulative absorption over 24 h amounted to 0.7 percent of the applied dose. The addition of 2 percent SEPA to the vehicle increased the 24 h absorption value to 23 percent of the applied dose (Marty et al. 1989). Furthermore, in comparative studies between SEPA and Azone, SEPA was shown to be a more effective human skin permeation enhancer for indomethacin (Figure 14.6, Marty et al. 1989). 

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