Лако-красочные материалы — производство

Most drug delivery systems are taken orally with the absorption of the drug occurring mainly in the proximal small intestine. To be effective either locally or systematically, a bioadhesive drug delivery system must be able to overcome the harsh gastric environment, motility of the gastrointestinal (GI) tract, immunogenic responses, enzymatic degradation, and dynamic changes in localization of the drug. The intestinal route is a desirable one despite these conditions because of its high absorptive characteristics compared to other routes of administration, which often need permeability enhancement of the tissue to increase bioavailability of the drug.

For a bioadhesive to adhere to either the stomach or intestine for an extended period of time, it must overcome the shear force associated with the motility patterns (parastalsis) of the GI tract, which can physically dislodge the adhesive from the mucus surface. GI motility patterns differ whether the subject is in a fasted (interdigestive) or a fed (digestive) state. Fasted-state motility has distinct phases of varying contractile magnitude, with the largest force occurring during what is called the housekeeper wave [38,39]. This phase serves to clear the upper GI tract of indigestible materials, and any bioadhesive system must therefore bind strongly enough to withstand this physical force if it is to be localized for an extended period of time. The digestive state motility pattern differs from the fasted state in that there are continuous contractions of approximately equal magnitude but only half the magnitude of the housekeeper wave. These continual contractions, as well as the physical removal of the bioadhesive by food, also need to be considered if a bioadhesive is to adhere to the mucus or underlying mucosal layer for an extended period of time.

The gastric turnover of mucin in both the fasted and fed state is a significant issue for bioadhesion in the oral route. The relatively rapid and continual production and subse­quent removal of older mucus by luminal peptic activity [40] makes long-term (i. e., 24 to 48 h) bioadhesion to the gastric mucin layer impractical. Some researchers have tried to deliver drugs to the intestine at a controlled rate using bioadhesives in the stomach [41,42] but because of the mucus exchange and the motility conditions discussed above, little can be expected in long-term gastric retention in humans.

Because of the high turnover rate of gastric mucin, for a bioadhesive to remain in the stomach for an extended period of time it would therefore need to adhere to the epithelial layer instead of the mucus. This has been exploited in the use of an antiulcer drug that can adhere to damaged gastric epithelial tissue. Ulcerations are formed in the gastric and intestinal regions, where the protective mucus layer has been altered, and the underlying tissue is thus subject to proteolytic degradation by pepsins and bacteria. The antiulcer drug Sucralfate is used for the treatment of peptic ulcers and has been shown to bind to damaged gastric mucosa [43]. Sucralfate, an aluminum salt of sulfated sucrose, has been shown to protect the gastric mucosa from noxious materials such as alcohol, aspirin, and nonsteroidal anti-inflammatory drugs (NSAIDs) [44-46]. Sucralfate polymerizes upon addition to acid and forms a viscous mass that binds to the gastric mucosa [47,48]. Its protective qualities against ulcerations are thought to be due to the enhancement of gel viscosity, hydrophobicity, and mucin content of the gastric mucus in the ulcer vicinity, as well as inhibition of prostaglandin synthetase [49].

Controlled intestinal release of drugs through the use of bioadhesives has certain advantages due to the high absorptivity and neutral pH of the intestinal lumen. Barring enzymatic and immunogenic responses, tissue absorption of drugs from a bioadhesive platform can be high if retained in the intestine for extended periods of time. In situ experiments in rats [50] have shown increased residence time of certain cross-linked acrylic polymers in the intestine. This increased residence time in the lumen of the intestine increased the bioavailability of poorly absorbed drugs.

Enzymatic and immunogenic degradation of both drug and bioadhesive must be addressed in any route of administration but seems to be very important in the GI tract. A detailed review of these parameters with regard to bioadhesion is beyond the scope of this chapter, but suffice it to say that any absorption of drugs via the intestinal epithelium presupposes adequate protection against enzymatic degradation associated with the stomach and intestine as well as immune responses to antigens in the GI tract. Another drawback to the gastrointestinal route is that drugs that enter the general circula­tion are subject to first-pass metabolism as they pass through the hepatic-portal system leading to lower systemic availability. Most of the work to date associated with bioadhe­sives in drug delivery systems has focused on other routes of administration, which avoid such adverse conditions.