**2.4 Gastrointestinal pH**

The GI pH influences the extent of ionization of drug molecules and thereby impacts on its absorption across the epithelium. Variations in pH across the GIT can be exploited for delayed drug release in desired section of the GIT in order to achieve efficient absorption. The fasted stomach is acidic, with pH range of 1–3, which increases upon food or liquid intake. Food is known to buffer the acidic content of the stomach. A rise in pH resumes in response to the continual gastric secretion and then finally, the pH reverts to the original levels due to gastric emptying of content; [40]. The gastric emptying rate significantly affects the rate of drug absorption because it regulates arrival in the duodenum, where the epithelial surface is suited for absorption [41]. Moreover, the disparity in gastric pH conditions affects the drug delivery behaviour of modified release dosage forms such as enteric coated products, where the onset of release along with the overall release kinetics may be changed [42].

The arrival of orally administered dosage forms into the small intestine is met by a pH of about 6 in the duodenum through to pH 7.4 at the terminal ileum [43]. This high pH variability is due to duodenal secretion of alkaline bicarbonate. During postprandial state, the initial intestinal pH drops due to the influx of acidic chyme, which is buffered by bicarbonate secretion as it travels distally [13]. Besides, the mean pH in proximal small intestine during the first hour of transit is usually 6.6, which is further decreased to 5–6 in the distal duodenum [44].

Typically, the pH in the caecum drops to just below pH 6 owing to the fermentation processes of the colonic microbiota and then rises to pH 7 at the rectum [42]. The drop in the amount of short chain fatty acids at the distal colon causes the

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 effective adsorption across the colon [47].
