Gastric media

Enteric-coated systems (ECS) utilize polymeric coatings that are insoluble in the gastric media and therefore, prevent or retard drug release in the stomach. Various types of ionizable polymers are commercially available. They dissolve at various pH ranging between 4.8 and 7.2. ECSs are generally applicable to four major types of drugs ... 

Literature describing simulated media for the fasted stomach and small intestine are available. In the fed state, the simulation of the fed stomach seems to be problematic because the composition is highly dependent on the associated meal. Therefore only a few publications of fed state gastric media are available. With regard to media simulating intestinal fluids in the fed state, several attempts have been made to develop suitable media, both with and without the addition of lipolysis product. 

We noticed a gradual swelling and disintegration of beads in the intestinal environment, after 30, 60, 90, and 120 min, from the successive incubations in acidic and neutral environments. Good similarities of density curves were observed in intestinal media compare to gastric media (Figure 33.1). 

Fig. 8.12 Comparison of drug-release profiles recorded in simulated gastric medium (pH =2) for (a) ibuprofen-AMP nanocomposite and (b) control sample (ibuprofen-talc suspension).

Pasquier, B., Armand, M., CasteUan, C., GuiUon, F., Borel, P., Lafont, H., and Lairon, D. (1996). Emulsification and lipolysis of triacylglycerols are altered by viscous soluble dietary fibres in acidic gastric medium in vitro. Biochem. J. 314, 269-275. 

Drug release was faster in artificial intestinal medium than in gastric medium (Table 3 Figs. 2 and 3). At pH 7.4, stearic acid can be slowly ionized in stearic ion. which is more soluble in water this could make the oil phase more permeable to the hydrophilic drug. 

The encapsulation of chitosan nanoparticles within liposomes and niosomes for its protection from low pH gastric medium was achieved by our group (Jain et al. 2006). It was hypothesized that though phospholipids or surfactants in vesicular form are thought to be unstable in the gastrointestinal environment, it has been reported that gastric lipases do not hydrolyze phospholipids or lipoidal surfactants. The digestion of these lipids takes place mainly in the small intestine by pancreatic lipase, colipase, phospholipase A2 and cholesterol esterase and by the action of bile salts. Thus, vesicular systems apparently provide protection to chitosan nanoparticles in the stomach, while in the intestine, the particles may get or remain encapsulated sequestered and taken by M-cells of the Peyer s patches due to their size as well as bioadhesive nature. 

Zaleplon P-CD RAMEB HPMC, PVP Spray-drying Hydrochloric acid medium with pH 1.2 (simulated gastric medium), phosphate buffer solution with pH 4.5 (simulated duodenal medium) and pH 6.8 (simulated intestinal fluid) HPMC enhanced the solubihzing and complexing ability of RAMEB, probably due to the formation of ZAL-RAMEB-HPMC ternary complex, while this enhancement was not observed for (3-CD and ZAL-RAMEB-PVP. [81]... 

Figure 12.8 In-vitro dissolution profiles of drug in simulated gastric medium without enzymes (pH 1.2) at 37°C from tablets formulated with microcrystaUine cellulose (TBL-MC) or mannitol (TBL-MN) loaded with ZAL, ZAL-RAMEB binary and ZAL-RAMEB-HPMC ternary complexes (mean SD n=9) [81].

The design of a proper delivery system requires a knowledge of the G.I.tract (i). The nature of the gastric acidic and enzymatic medium has been elucidated. More recently Davis (2) and Harris (3) have studied the rate of emptying of the stomach. Dressman (4) has clinically followed pH variations in both the empty stomach and after a meal finding that sinusoidal pH reductions occur during mastication of solid food, whereas the duodenum maintains a relatively constant pH during introduction of the chyme. 

A typical example is ibuprofen. The BCS-relevant characteristics of the drug are given in Table 5. Obviously, there will be little or no dissolution of ibuprofen under typical gastric conditions in the fasted state. However, the D S falls almost within the BCS limit of < 250 mL at pH 6.8, so it can be assumed that dissolution into a standard volume of medium (e.g., 500 mL, as recommended in Table 3) can be completed. This assumption is borne out by the results for dissolution of the pure drug and several IR oral drug products available on the European market as shown in Figure 4. 

To test the robustness of the formulation to variations in gastric pH, dissolution results should be obtained in both the pH 2 medium described in Table 3 and a model which reflects the conditions in the hypochlohydric stomach. A good choice would be acetate buffer adjusted to pH 5 and having a very low buffer capacity, since hypochlorhydria is generated by a reduction in HCl secretion rather than the addition of buffer species. 

The transfer model (15) can be used to answer the question of whether the drug is successfully released in the stomach, only to precipitate when it moves into the higher pH environment of the small intestine. As depicted in Figure 8, the pure drug (or formulation) is added to a gastric simulating medium at time zero, after which it is allowed to dissolve and simultaneously transferred into a second vessel containing FaSSIF or other suitable biorelevant medium. 

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