A new concept in colonic drug targeting: a combined pH-responsive and bacterially-triggered drug delivery technology.
BACKGROUND
Current approaches to colonic drug delivery exploit one of two main physiological characteristics: the pH change or increase in bacterial numbers along the gastrointestinal tract. Here, we describe a new concept in targeted delivery, which combines these triggers to improve colonic delivery.


OBJECTIVE
To assess the in-vivo targeting performance of a novel colonic delivery coating comprising a mixture of pH-responsive enteric polymer (Eudragit S) and biodegradable polysaccharide (resistant starch) in a single layer matrix film.


METHODS
Tablets (radio-labelled) were film-coated with the dual-mechanism coating and administered in a three-way crossover study to eight healthy volunteers (i) without food, (ii) with breakfast or (iii) 30 min before breakfast. The site of intestinal disintegration was assessed using gamma scintigraphy.


RESULTS
The coated tablets were able to resist breakdown in the stomach and small intestine. Consistent disintegration of the dosage form was seen at the ileocaecal junction/large intestine. The site of disintegration remained unaffected by feeding.


CONCLUSIONS
The dual-mechanism (pH/bacterial) coating provides colon-specificity. Each trigger mechanism has the capacity to act as a failsafe, ensuring appropriate targeting in the gastrointestinal tract. This platform technology has potential for systemic applications or the treatment of local disorders of the large intestine, such as inflammatory bowel disease.
Ibekwe
V C
VC
Department of Pharmaceutics, The School of Pharmacy, University of London, London, UK.
Khela
M K
MK
Evans
D F
DF
Basit
A W
AW
D000328:Adult; D000704:Analysis of Variance; D044682:Colon, Ascending / Q000378:metabolism* / Q000382:microbiology; D016503:Drug Delivery Systems; D004755:Enterobacteriaceae / Q000378:metabolism*; D005502:Food; D005772:Gastrointestinal Transit; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007553:Isotope Labeling; D008297:Male; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated