**2.5 GIT transit time**

Generally, the GIT transit time of most orally administered doses through buccal cavity and oesophagus is transient. The stomach is naturally the first segment of the GIT, wherein disintegration and dissolution of solids such as drugs and formulations occur [42]. The period required for a dosage form to exit the stomach is inconstant and relies on several physiological factors, such as age, body posture, gender and food intake [48]. Gastric transit can span from 0 to 2 h in the fasted state and can be extended up to 6 h after food intake [47]. The small intestine is the region of choice for drug absorption with a transit time ranging from 2 to 6 h in healthy individuals. The dissolution of poorly soluble, weakly acidic compounds and lipophilic compounds is greatly enhanced in this region [13]. In colon-specific drug delivery, the drug has to cross the whole GIT prior to arrival at the colon. Thus, the transit time across the colon can be highly variable, and ranges from 20 to 56 h in healthy humans, although higher variations are also reported in literature amounting up to 72 h [42, 49, 50]. Variations in colonic transit time are affected by dosing time, bowel movements as well as gender, whereby females generally have longer colonic transit times than males [51, 52].

## **2.6 Gut microbiome**

Enzymatic and microbial degradation of GIT content affects the amount ultimately made available for absorption. The active sites for most endogenous enzymes are the stomach and small intestine. Even though these enzymes may affect the stability of orally administered drugs, it is possible to exploit this property for regional drug delivery of formulations in the GIT [47]. On the other hand, the intestinal microbiome which includes 500–1000 bacterial species is also important for the digestion of food and the metabolism of drugs [53]. Gastrointestinal microbiome is found in both upper and lower GIT, whereby, a lower bacterial number (1013–1014 bacteria mL−1 of intestinal content) is in the upper GIT because of the fast luminal flow, intestinal fluid volume, and the secretion of bactericidal compounds in this part of the GIT, and highest bacterial community (1010–1011 bacteria mL−1 of intestinal content) is in the colon, in which the redox potential is low and the transit time is long [54, 55]. Therefore, greater number of the intestinal microbiome exists in the anaerobic colon, in which the fermentation of carbohydrates contributes to their nourishment. Usually, orally administered drugs are transformed to bioactive, bio-inactive, or toxic metabolites by the gut microbial population, all of which can impede the bioavailability of drug. However, gut microflora can improve drug bioavailability by eliminating polar moiety from derived conjugates and thereby promoting biliary recycling of compounds [13].

Thus, formulation scientist must be cognizant of the interplay between drug and physiological and anatomical manifestations within the GIT when designing orally administered dosage forms. For example, enteric coating can be applied to dosage forms to delay the release of the API in the acidic gastric fluid until pH above 5.0 [56]. Enteric coating may also be used to shield acid-labile drugs from gastric

**33**

*Gastrointestinal Delivery of APIs from Chitosan Nanoparticles*

traction more recently is the employment of nanoparticles.

ability to attain the following key attributes [60]:

for effective deployment of APIs in the GIT [14, 64].

• The NP must be able to bind or contain the appropriate drug.

therapeutics and only release the drug once at the required site.

inert material with a limited lifespan to allow safe degradation.

distress, and upon arrival to the alkaline pH milieu, the enteric polymer coating disintegrates within the intestinal fluid, releasing the drug [57]. Despite employing such coatings and other conventional interventions, numerous pharmaceuticals still display insufficient bioavailability through the oral route of administration. This necessitates the use of alternate strategies. One area of research that is gaining

Nanoparticle technology is a multidisciplinary field that utilizes principles from chemistry, biology, physics and engineering to design and fabricate submicronic (< 1 μm) colloidal systems [58]. Nanotechnology has several pharmaceutical and medical applications wherein nanoparticles (NPs), with sizes comparable to large biological molecules such as enzymes can be employed in the delivery of therapeutic agents [59]. The effectiveness of the nanoscale drug delivery vehicles lies on their

• The nanocarrier must stay stable in the serum to allow systemic delivery of the

• The NP-drug complex has to reach the required site either via receptor-mediated interactions or by the enhanced permeability and retention (EPR) effect.

• The residual NP carrier should ideally be made of a biological or biologically

There are several types of NP drug delivery systems, which may be broadly divided as organic and inorganic NPs [61]. Their particle size, surface charge (ζ potential), hydrophilicity/hydrophobicity, composition, etc. can be tailored for a diverse applications [62]. The primary consideration when designing orally administered NP drug delivery system is to maximise drug concentration in the GI

Organic NP (**Figure 2**) are solid particles comprised of organic compounds (usually lipidic or polymeric) ranging from 10 nm to 1 μm [63]. They can be formulated by simple techniques to encapsulate therapeutic agents. Preferably, compounds used in formulation of organic NPs should be biodegradable and biocompatible [61]. Manifestations of organic NP include liposomal, polymeric and solid lipid NP, each system possessing requisite features that addresses physiological and anatomic constraints addressed in sections above. In addition, others systems such as micelles, dendrimers etc. have been also explored as effective nanocarriers

Inorganic NP represent a wide spectrum of systems synthesized from metals, metal oxides, and metal sulphides [65]. Gold, silica and superparamagnetic oxide NP are among the long list of inorganic NP (**Figure 3**). They have been studied for

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

**3. Nanoparticle technology**

therapeutic window.

**3.1 Oral organic NP**

**3.2 Oral inorganic NP**

distress, and upon arrival to the alkaline pH milieu, the enteric polymer coating disintegrates within the intestinal fluid, releasing the drug [57]. Despite employing such coatings and other conventional interventions, numerous pharmaceuticals still display insufficient bioavailability through the oral route of administration. This necessitates the use of alternate strategies. One area of research that is gaining traction more recently is the employment of nanoparticles.
