Pharmaceutical Manufacturing Handbook: Production and

354 CONTROLLED-RELEASE DOSAGE FORMS
The role of the stomach in drug and nutrition absorption is very limited, and it
acts primarily as a reception area for oral dosage forms. Nonionic, lipophilic molecules
of moderate size can be absorbed through the stomach only to a limited extent
owing to the small epithelial surface area and the short duration of contact with the
stomach epithelium in comparison with the intestine [17] . The transit time in the GI
tract varies from one person to another and also depends upon the physical properties
of the object ingested and the physiological conditions of the alimentary canal
(Table 1 ). After passing through the stomach, the next organ that a drug or bioactive
compound encounters is the small intestine. The intestinal epithelium is composed
of absorptive cells (enterocytes) interspersed with goblet cells (specialized for mucus
secretion) and a few enteroendocrine cells (that release hormones). The enterocytes
of intestinal epithelium are the most important cells in view of the absorption of
drugs and nutrients [18] . Histologically, colonic mucosa resembles the small intestinal
mucosa, the absence of villi being the major difference [19] . The microvilli of
the large intestine enterocytes are less organized than those of the small intestine.
The resulting decrease in the surface area of the colon leads to a low absorption
potential in comparison with the small intestine. However, the colonic residence
time is longer than that for the small intestine, providing extended periods of time
for the slow absorption of drugs and nutrients [20] . Figure 2 shows the various
physiological processes encountered by an orally administered drug during the
course of GI transit.
5.1.5.2 Fundamentals of Controlled - Release Oral Dosage Forms
Oral controlled drug delivery is a system that provides the continuous delivery of
drugs at predictable and reproducible kinetics for a predetermined period throughout
the course of GI transit [21] . Also included are systems that target the delivery
of a drug to a specifi c region within the gastrointestinal tract (GIT) for either local
or a systemic action. All the oral controlled drug delivery systems have limited utilization
in the GI controlled administration of drugs if the systems cannot remain
in the vicinity of the absorption site for the lifetime of the drug delivery. In the
exploration of oral controlled - release dosage forms, one encounters three areas of
potential challenges [22] :
1.
2.
TABLE 1
Dynamics
Region
Stomach
Small intestine
Large intestine
Gastrointestinal Tract: Physical Dimensions and
Surface area (m 2 )
0.1 – 0.2
100
0.5 – 1
Drug Delivery System To develop a viable oral controlled - release drug delivery
system capable of delivering a drug at a therapeutically effective rate to a
desirable site for the duration required for optimal effi cacy.
Modulation of GI Transit Time To modulate the GI transit time so that the
drug delivery system developed can be transported to a target site or to the
pH
1.2
6.8
7.5
Transit Time
Fluid Solid
50 min 8 h
2 – 6 h 4 – 9 h
2 – 6 h 3 – 72 h