Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy.

Optimized floating (F) and non-floating (NF) hydrophilic matrix capsules have been characterized in vitro with regard to their buoyancy or non-buoyancy capabilities and their diametral size evolution with time. The gastric residence times (GRTs) and transit behaviors of these F and NF forms prepared in small, medium, and large sizes were then comparatively examined in fed volunteers remaining either upright or supine. The results show that all the optimized F forms do lastingly float upon the gastric contents, whereas the NF forms sink rapidly after ingestion. In upright subjects, the F forms are consequently protected against postprandial emptying. The GRTs of the NF forms are much more variable and highly dependent on their size (mean GRT small < medium < large units, p < 0.05). The GRT prolongation obtained with the F forms when compared with the NF ones is hence significantly marked for the small and medium size dosage forms (p < 0.05) but not for the large ones (p > or = 0.05). In supine subjects, a size effect influences the GRT of both the F and NF forms (p < 0.05). The F forms are more often emptied before the NF ones but, size for size, the mean GRTs do not differ in the aggregate. These findings, together with literature data, are used to explain why a number of former investigations have come to contradictory conclusions about the effect of density of an undigestible form on GRT. Uncontrolled factors are hiding from disclosure the GRT enhancement that should be observed when optimized F forms are used within defined conditions.