Pharmaceutical Manufacturing Handbook: Production and

Degradation
Liver
Hydrolytic
Enzymatic
Ileum
Jejunum
Colon
CONTROLLED-RELEASE ORAL DOSAGE FORMS 355
Rectum
Complexation
Degradation within
wall
Hydrolytic
Enzymatic
Microbial
Stomach
Absorption
Adsorption
Enterohepatic
recycling
Absorption
Absorption
Absorption
Absorption
Pportal vein
FIGURE 2 Physical model illustrating various physiological processes during gastrointestinal
transit.
vicinity of an absorption site and reside there for a prolonged period of time
to maximize the delivery of a drug dose.
3. Minimization of Hepatic First - Pass Elimination If the drug to be delivered
is subjected to extensive hepatic fi rst - pass elimination, preventive measures
should be devised to either bypass or minimize the extent of hepatic metabolic
effect.
With most orally administered drugs, targeting is not a primary concern, and it
is usually intended for drugs to permeate to the general circulation and perfuse to
other body tissues, except it is medicated intentionally for localized effects in the
GIT. There is a general assumption that increasing concentration at the absorption
site will increase the rate of absorption and, therefore, increase circulating blood
levels, which in turn promotes greater concentrations of drug at the site of action.
If toxicity is not an issue, therapeutic levels can thus be extended as shown in Figure
3 . In essence, “ drug delivery ” by these systems usually depends on release from
specifi c types of dosage forms and permeation through an epithelial membrane to
the blood. Still, the biological and physicochemical factors that come across play
important roles in the design of such systems. The physicochemical properties have
been described earlier in this chapter while biological factors involved with oral
dosage forms will be described below.
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