The effects of pharmaceutical excipients on small intestinal transit.

Abstract

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)

Evaluation and suggested improvements of the Biopharmaceutics Classification System (BCS)

“…The BCS-limit for high k diss is ~14-fold more rapid than for k pe (3.8 h −1 vs 0.27 h −1 ) (Note: Adkin et al (1995) estimated the gastric emptying rate constant for solutions to be 3.8 h −1 .) The difference is even greater when assuming 85% absorption (instead of 90%) or a 40-h intestinal transit time (instead of 8.4 h).…”

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension

“…However, the reported effects of formulation excipients on efflux inhibitors are not clearly defined, especially not in-vivo (Polli et al 2004). Furthermore, the effect on gastrointestinal transit by large amounts of sugars has been highlighted as another issue, especially for liquid formulations where large amounts of such excipients may be included (Adkin et al 1995;Yu et al 2002;Basit et al 2004).…”

Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs

“…Historically, excipients were considered inert substances that could be used mainly in the manufacture of drug products as diluents, fillers, binders, lubricants, coatings, solvents, and dyes (7). However, with the advances in pharmaceutical science, some "active" excipients have been found to be capable of influencing drug absorption or bioavailability through a variety of mechanisms, such as modification in solubility/dissolution, change in intestinal permeability (including transporters), and modulation of gastrointestinal (GI) motility (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). To further investigate the effects of "active" excipients on the absorption of BCS class III drugs, this paper examines those that may modulate GI motility and affect the transit time of drugs in the gut.…”