Effect of dosing time on the total intestinal transit time of non-disintegrating systems

Abstract

The total gastrointestinal transit time of nondisintegrating tablets may be affected by dosing time; available literature on this topic is inconclusive. OROS® systems are nondisintegrating osmotically driven tablets that release drug over a period of time during their transit through the gastrointestinal tract and are excreted intact in the feces. Total transit times following morning administration of OROS® systems pooled from various studies ( n=1163 systems) showed a distribution with peak frequencies clustering around 24 and 48 h and following night administration ( n=80 systems) was found to cluster around 12 and 36 h. The total transit time distribution appears to be different following morning and night administration. However, on reanalyzing the data considering clock time when the tablet was collected rather than time post-administration, most of the difference between the distribution patterns disappeared. This suggested that total transit times after morning or night administration may be related to the bowel movement habits of the study population. Therefore, OROS® systems total transit time were compared to the intrinsic bowel movement pattern of the general population reported in the literature and indeed a good correlation was seen between the two. The total transit time appears to be determined by two factors: the defecation frequency and the probability of its inclusion in the defecation event which is related to its location in the GI tract. A tablet is more likely to be excreted if it is further down in the GI tract. The total transit time data for OROS® systems suggest that with the morning dosing the tablet is more likely to be excreted in the bowel movement the next morning. With the night time dosing the tablet may not be far enough in the colon to be excreted in the next morning bowel movement and therefore, it is more likely to be excreted the following morning.