In vivo evaluation of a novel pH- and time-based multiunit colonic drug delivery system.
BACKGROUND
Targeted drug delivery to the colon is important for topical treatment of inflammatory bowel diseases. Established targeting systems predominantly focus on either pH- or time-dependent release, or bacterial degradation.


OBJECTIVE
To perform a three-phase, crossover design trial evaluating a novel combined pH- and time-based multiunit delivery system.


METHODS
Twelve healthy male volunteers each received 200 mg of caffeine as either uncoated immediate release tablets, coated pellets with pH-dependent rapid release (EUDRAGIT FS 30D), and pellets with pH- and time-based release (inner layer EUDRAGIT RL/RS 30D; outer layer EUDRAGIT FS 30D). Orocecal transit time was measured using lactose-[13C]ureide. Serum concentrations of caffeine were measured by high-performance liquid chromatography.


RESULTS
In contrast to the uncoated tablet, both coated systems reached the ileocecal region almost at the same time (3.19 +/- 0.71 and 3.33 +/- 0.81 h). Serum caffeine profiles were significantly prolonged for the pH and time delivery system compared with the pH-only based system (median tmax 12.0 vs. 5.5 h; P < 0.001). This was further reflected by a lower Cmax value and a lower area under the curve within 24 h after application.


CONCLUSIONS
Compared with the conventional delivery systems, drug release from the new dosage form may offer a new dimension for the oral treatment of mid to distal ulcerative colitis.
2nd Department of Medicine, JW Goethe University, Frankfurt/Main, Germany.
C
C
Bott
M W
MW
Rudolph
A R J
AR
Schneider
S
S
Schirrmacher
B
B
Skalsky
H-U
HU
Petereit
P
P
Langguth
J B
JB
Dressman
J
J
Stein
D000284:Administration, Oral; D002110:Caffeine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000592:standards*; D004343:Drug Implants; D005772:Gastrointestinal Transit / Q000502:physiology; D005782:Gels; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male
D003692:Delayed-Action Preparations; D004343:Drug Implants; D005782:Gels; D002110:Caffeine