Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems - Pharmaceutical Technology

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Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems
Novel hydrophobic bioadhesive polymers and dosage designs are now available to effectively achieve tailored release kinetics of a broad range of drugs to meet the clinical needs.


Pharmaceutical Technology
Volume 32, Issue 11, pp. 100-121


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.)
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).

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).


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.)
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.

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).


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