Targeting to the colon.
The need to target drugs to the colon is well recognized and considered to be an effective approach in the treatment of local
disorders such as irritable bowl syndrome and inflammatory bowl diseases such as Crohn's disease and ulcerative colitis. It
is also a preferred absorption site for oral administration of protein and peptide drugs because of relatively low proteolytic
enzyme activity (38).
Figure 7: Plasma pramipexole profile following administration of pramipexole bioadhesive extended release (XR) capsules, 0.375
mg, given once daily versus Mirapex tablets, 0.125 mg given three times daily to health volunteers, n = 12 (37). (ALL FIGURES
AND TABLES ARE COURTESY OF THE AUTHOR.)
Because of its lower mucin turnover and lower sensitivity to mucus secretory stimulus, the colon is a suitable location for
bioadhesion in the GIT (13). Slow transit of dosage forms through the colon will prolong contact time between the formulation
and the absorptive surface, thereby enhancing drug exposure. This has led to the development of oral dosage forms for selective
drug delivery for various colonic conditions. Typically, systems have been designed to release drugs rapidly in the upper
portion of the colon. However, this may result in unnecessary exposure of drug to noninflamed tissues, thereby reducing the
efficiency at the desired site of inflammation and increasing adverse effects. Therefore, a colon-specific bioadhesive multiparticulate
delivery system that remains at the inflamed target site for a prolonged period of time will provide drug exposure in the
local mucosa and reduce the potential for side effects (39). Achieving desired levels of drug exposure at the inflammatory
target site requires careful considerations in terms of the intersubject variabilities in intestinal transit time, intraluminal
pH profile, disease pattern, and drug disposition (40).
At Spherics, an effort of exploiting Spheromer bioadhesive polymers to target delivery to distal parts of the GIT has been
conducted. Proof-of-concept studies have been completed with promising results. In fluoroscopic studies in beagle dogs, bioadhesive
beads coated with Spheromer bioadhesive polymers uniformly lined the ascending large bowel and remained in close apposition
to colonic mucosa without mixing with digested food contents (see Figure 8). In contrast, beads coated with non-bioadhesive
cellulose acetate polymer were evenly distributed in the lower small bowel, mixed with food, moved freely with the peristaltic
movements, and did not attach to the intestinal mucosa.
Figure 8: Spheromer-coated multiparticulate beads lining the large colon 8 h postdosing (top) and control non-bioadhesive
multiparticulate beads 8 h postdosing (bottom). (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
A colonic-specific bioadhesive system should prevent drug release in the stomach and small intestine and provide rapid adhesion
and drug release upon reaching the colon. The selection of triggering mechanisms (e.g., prodrug, pH, or microflora activated)
that respond to the physiological conditions in the colon should be carefully selected such that the bioadhesive performance
of the system remains unaffected.
Targeting to the rectum.
Although peroral administration is the most common route for targeting drugs, oral administration may not be feasible. Use
of a bioadhesive liquid suppository, based on in situ gelling phenomenon, has been explored as an option for the local treatment of diseases of the anorectal area as well as for
systemic drug delivery (41–44). Choi examined a bioadhesive liquid suppository that combined a bioadhesive polymer with a
thermal gelling polymer. With acetaminophen as a model compound, a bioadhesive system that gelled strongly at physiological
temperature gave the most prolonged plasma level of acetaminophen in vivo (45).