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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.
Nov 2, 2008 By:
Avinash Nangia, PhD Pharmaceutical Technology
Volume 32,
Issue 11,
pp. 100-121
Strategies for successful drug delivery to the esophagus should involve drugs that are readily soluble in bioadhesive polymers,
rapidly smear the esophageal epithelium, and are not washed away by the flow of saliva and other liquids. The risk of bioadhesive
dosage forms getting dislodged in the esophagus when taken with little or no water could also pose problems and should be
considered as part of the formulation design (30). These problems, attributed to esophageal blockage or drug-induced injuries
resulting from a high concentration of drag at the epithelium layer corrosive to the local tissue, may have serious clinical
implications.
Targeting to the stomach and small intestine. One of the feasible approaches for achieving a prolonged and predictable release profile in the GIT is to maintain the dosage
form in the stomach over an extended duration. This is of great importance for drugs in which the absorption site is restricted
to the stomach or the proximal small intestine. Specifically, it is important for controlled-release dosage forms designed
to deliver drugs to narrow absorption windows (e.g., levodopa, metformin, furosemide, gabapentin, and amoxicillin). A bioadhesive
dosage form for gastric delivery should achieve a rapid interaction with the mucosal surface and be sufficiently strong to
resist the propulsion forces of the stomach wall. The effectiveness of the system also should be maintained irrespective of
continuous production of mucus by the gastric mucosa to replenish the mucus that is lost through peristaltic contractions,
as well as dilution of the stomach contents.
Figure 2: X-ray images of barium sulfate spheres (bioadhesive and control non-bioadhesive) taken at different time intervals
in fasted beagles (34). At 1.5 h: bioadhesive spheres retained in the stomach while control spheres are entering the intestine;
at 4.5 h: bioadhesive spheres in the stomach while control spheres entering ascending colon; at 8.5 h: bioadhesive spheres
scattered evenly in stomach, small and large intestine, while control spheres are in distal descending colon; at 24 h: bioadhesive
spheres still present in the intestine and no control spheres in the intestine. (ALL FIGURES AND TABLES ARE COURTESY OF THE
AUTHOR.)
Few studies have been conducted to specifically investigate the transit time of oral bioadhesive tablet formulations containing
hydrophilic polymers in animals and humans. An increase in transit time and improved absorption of griseofulvin, by three-
to four-fold was observed from a bioadhesive oral dosage form containing a cross-linked acrylic acid polymer as the bioadhesive
material (31). In a radioscintigraphic study (32), two different capsule formulations, based on the hydrophilic bioadhesive
polymers polycarbophil and Carbopol, were evaluated for gastric emptying and small intestine transit time. Results indicated
that both bioadhesive formulations were not dramatically different from the nonadhesive controlled formulation in terms of
stomach emptying, small intestinal transit time, and time to reach the colon. Similar results were obtained with an oral bioadhesive
controlled-release formulation of furosemide (33). A bioadhesive formulation containing Carbopol 934 and furosemide, a model
drug with erratic absorption and a narrow absorption window, was evaluated in a radioscintigraphy transit time study in humans.
The extent of absorption from the bioadhesive formulation was less than the control non-bioadhesive formulation. The reasons
suggested for this poor performance were that in vivo adhesive properties were insufficient to overcome the powerful gastric contractions during Phase III of the housekeeping
motor migrating complex waves in the fasted state. Clearly, the applications of hydrophilic polymers in designing oral dosage
forms, in particular, controlled-release dosage forms, has been limited.
Avinash Nangia, PhD, is senior vice-president of research and development at Spherics, Inc., 375 Forbes Blvd., Mansfield, MA 02048, tel. 508.452.7000, fax 508.452.7070.
Articles by Avinash Nangia, PhD
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