**2. The GIT**

The GIT, also known as the digestive tract or alimentary canal, is approximately 9 meters long and can be functionally divided into two parts, the upper and the lower GIT (**Figure 1**). The upper GIT; consisting of mouth, pharynx, oesophagus, stomach and small intestine, play a major role in the transport of the swallowed food bolus, enzymatic digestion and absorption of nutrients [18]. The lower GIT is usually referred to the large intestine and is responsible for the adsorption of water, fermentation of undigested sugars and the storage and evacuation of stool [19]. Following oral dosing, the drug traverses several semipermeable cell membranes through its trajectory to absorption and eventually enters the general circulatory system. Drugs cross cell membranes, which comprise of bimolecular lipid matrix, either by passive diffusion or active transport.

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*Gastrointestinal Delivery of APIs from Chitosan Nanoparticles*

The most prevalent form of absorption of the majority of orally administered drugs is by passive diffusion across cell membranes. This process comprises of a three-step process, whereby the permeant first transverses into the membrane, disperses across it and then is released into the cytosol [20]. Typically, drug molecules move down a concentration gradient, from a region of high concentration (e.g., GI fluids) to one of low concentration (e.g., blood), without the expenditure of energy [21]. Usually, a concentration gradient is manifested as a disparity in concentration of a substance within an area and is linearly related to the diffusion rate. The latter is also governed by the lipid solubility, size and polarity of the drug species.

Most drugs are either weak acids or bases and occur either in the unionized or ionized form as a function of pH [22]. For lipophilic drugs, the unionized form of drug, may penetrate cell membranes easily as the membrane is lipoidal. On the other hand, hydrophilic drugs, present an ionized form of the drug, which has high electrical resistance and thus cannot traverse the cell membranes easily but may diffuse through the para-cellular spaces. However, it is worth noting that the para-cellular junctions contribute to less than 0.01% of the entire GIT surface area and furthermore, the permeability of these junctures diminishes down the GIT [23]. Additionally, the capability of drugs to traverse a membrane also relies on the acid–base dissociation constant (pKa) of the drug in question. The pKa is the pH at which concentrations of ionized and unionized forms are equivalent [24]. So, if the pH is less than the pKa, the unionized form of a weak acid prevails, and *vice versa* for weak bases. Henceforth, when a weak acid is administered orally, nearly all the drug in the stomach remains unionized, preferring diffusion via the gastric mucosa. On the other hand, for a weak bases with a pKa = 4.4, majority of the drug in the

Overall, the process by which molecules traverse cell membranes is by passive diffusion, down the concentration gradient. However large hydrophilic ionic molecules and charged molecules cannot freely traverse the phospholipid bilayer cell membrane passively. Their transport may be confined to protein channels and distinct transport mechanisms present within the membrane [25]. Such drugs gain access through the membrane by facilitated diffusion whereby molecules integrate with embedded protein carriers to shuttle them across the membrane. This process does not expend energy and is also down the concentration gradient though quicker than

*DOI: http://dx.doi.org/10.5772/intechopen.95363*

**2.1 Passive diffusion**

*The anatomy of the human gastrointestinal tract.*

**Figure 1.**

stomach will be ionized [21].

**Figure 1.** *The anatomy of the human gastrointestinal tract.*
