The effects of pharmaceutical excipients on small intestinal transit.
1. The effect of three iso-osmotic pharmaceutical excipient solutions on gastrointestinal transit were investigated in eight healthy male volunteers. Each subject received 200 ml radiolabelled purified water, or a 200 ml solution of sodium acid pyrophosphate ((SAPP) 1.1 g/200 ml), mannitol (2.264 g/200 ml) or sucrose (4.08 g/200 ml) in a four way cross over design. On each of the study days the volunteers also received five 6 mm diameter non-disintegrating tablets. Dual isotope gamma scintigraphy was used to assess the transit behaviour of the tablets and solutions. 2. There were no significant differences between the gastric emptying times of the four solution formulations. Rapid gastric emptying was observed in all cases (mean t 50% varied from 11-14 min). 3. Small intestinal transit (SIT) times for the SAPP and mannitol solutions were reduced by 39 and 34%, respectively, when compared with the control solution (purified water = 240 min; SAPP = 147 min; mannitol = 158 min). The 95% confidence limits for the mean differences in SIT time between the control and SAPP solutions was 39-94-149 min, and 40-82-124 min between the mannitol and the control. Intestinal transit for the sucrose solution was similar to that for the control solution (sucrose = 229 min). 4. There were no significant differences in the transit times of the non-disintegrating tablet preparations, when co-administered with each solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Adkin
D A
DA
Department of Pharmaceutical Sciences, University of Nottingham, University Park.
Davis
S S
SS
Sparrow
R A
RA
Huckle
P D
PD
Phillips
A J
AJ
Wilding
I R
IR
D000328:Adult; D018592:Cross-Over Studies; D011756:Diphosphates / Q000008:administration & dosage / Q000494:pharmacology; D005079:Excipients / Q000008:administration & dosage / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007421:Intestine, Small / Q000000981:diagnostic imaging / Q000187:drug effects*; D007553:Isotope Labeling; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D011877:Radionuclide Imaging; D013395:Sucrose / Q000008:administration & dosage / Q000494:pharmacology; D014867:Water / Q000008:administration & dosage / Q000494:pharmacology
D011756:Diphosphates; D005079:Excipients; D014867:Water; D008353:Mannitol; D013395:Sucrose; C003319:sodium pyrophosphate