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July 05-06, 2019 | Paris, France
Pharmaceutics and Advanced Drug Delivery Systems
2
nd
International Conference and Exhibition on
Asian Journal of Biomedical and Pharmaceutical Sciences | ISSN:2249-622X | Volume 9
Gut motility, transit and pH: How different are we?
Hala M Fadda
Butler University, USA
S
mall intestine (SI) motility, transit times and pH can have
implications on the absorption of poorly soluble drugs.
Utilizing novel approaches, we investigated these physiological
parameters in humans. The small bowel video capsule
endoscope (VCE) allows visualization of the entire SI and the
wireless motility capsule (SmartPill™, Medtronic, Minneapolis,
MN) houses sensors that provide real-time measurements of
temperature,pressureandpHoftheimmediategastrointestinal
(GI) luminal environment. Our findings illustrate that in some
healthy subjects, pH in the proximal SI does not rise uniformly
but is characterized by large fluctuations. In a third of healthy
subjects, the pHmedian was 6.0 (5th, 95th percentiles 3.09,
7.06) and fluctuated over a mean period of 28 min. These
pH changes can have implications on the supersaturation
and precipitation of weakly basic drugs. Large inter-individual
variability in the frequency of pressure activity (Ct) and area
under the pressure curve (AUC) is observed in the proximal
SI of healthy subjects and patients with constipation. Median
AUC was 3996 mmHg s−1 (5th, 95th percentiles 948, 16866
mmHg s−1) in these two populations combined. An inverse
correlation was observed between AUC and small intestinal
transit times (SITT) at r=−0.49, p < 1×10−6, that is a moderate
correlation suggesting longer SITT with lower pressure activity.
The inter-individual variations in SI pressure activity may have
implications on the disintegration/dissolution of oral modified
release (MR) dosage forms. Themedian SITTof human subjects
as determined using VCEwas 208min, with times ranging from
50 to 460 min. This large inter-subject variability in transit
times may explain the variability in bioavailability observed
from some MR preparations. Our improved understanding of
GI transit times, pH and pressure activities can be utilized in in
silico and in vitro drug release and absorption models for oral
drug delivery systems.
e
:
hfadda@butler.eduAsian J Biomed Pharmaceut Sci, | ISSN: 2249-622X
Volume 9