**3. Nanoparticle technology**

*Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

tive adsorption across the colon [47].

longer colonic transit times than males [51, 52].

promoting biliary recycling of compounds [13].

**2.5 GIT transit time**

**2.6 Gut microbiome**

secretion of colonic mucosal bicarbonate that leads to a neutral pH. Short chain fatty acids are the end products of fermentation of dietary fibres by the anaerobic intestinal microbiota [45]. As a consequence of the neutral pH of the colonic luminal fluid, the solubilisation of drug is the rate-limiting factor in colonic drug absorption [46]. The unspecific interactions of drugs with colonic content (e.g. dietary residues, intestinal secretions or faecal matter) all adds to the odds of effec-

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

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

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

**32**

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 ability to attain the following key attributes [60]:


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 therapeutic window.
