Drug Targeting Organ-Specific Strategies

162 6 A Practical Approach in the Design of Colon-specific Drug Delivery Systems
small intestine and dissolve only in the colon, depending on their dissolution pH and the
thickness of the coating applied. Many of the oral drug preparations for the treatment of inflammatory
bowel disease available on the market (e.g. Asacolitin ® , Claversal ® , Salofalk ® )
are coated with enteric polymers such as Eudragit ® L or S, i.e. methacrylic acid copolymers
with different degrees of substitution, which show pH-dependent dissolution behaviour.
These polymers are supposed to induce drug release as soon as the luminal pH in the GI tract
exceeds values of 6 or 7. However, studies with Eudragit ® S-coated tablets in healthy subjects
have shown, that drug release in the colon is not sufficiently reproducible [14,15]. Other studies
verify the reliability of this delivery method. One reason for these inconsistent results is
the decrease in the luminal pH after passage through the ileocaecal valve as a result of bacterial
fermentation of non-absorbable oligo- and polysaccharides to short chain fatty acids.
Only in the distal colon is a luminal pH of 7 attained, which differs only slightly from the average
pH of the small intestine (6.5–6.8).
The OROS-CT delivery system (Oral Osmotic System for Colon Targeting) is an enteric
formulation consisting of one drug compartment containing osmotically active excipients
and a second compartment containing a swelling polymer (Figure 6.3). Both compartments
are coated with a semi-permeable membrane and an outer enteric coating. After dissolution
of the enteric coating the swelling polymer slowly pushes the liquid content of the
osmotic compartment out of the micropore as a result of water penetration. This leads to
combined pH-controlled and sustained drug release.
During an acute attack of inflammatory bowel disease the luminal pH of the large intestine
which is normally 6.4–7.0, drops to values between 2.3 and 4.7 [17–19], which means that
enteric coatings are unsuitable coating materials in this particular case. Coating materials
that dissolve at a low pH or are degradable in an acidic environment may be used in such a
case.Therefore, the basic polymers Eudragit ® E, an aminoalkyl methacrylate copolymer, and
polyvinylacetal diethylaminoacetate (AEA) have been investigated in vitro as coating materials
for oral dosage forms designed for the treatment of inflammatory bowel disease with
dexamethasone as the model corticosteroid [20,21]. An in vivo study is planned.
Micropore
Semipermeable
membrane
OROS-CT COER-24
Drug +
Osmotic agent
Enteric coating
Swelling agent
Micropore
Drug compartment
Polymer delay coat
Osmotic compartment
Semipermeable membrane
Figure 6.3. OROS-CT TM (Oral Osmotic System for Colon Targeting) and COER-24 TM (Controlled
Onset Extended Release) delivery systems.