Abstract
Gastrointestinal luminal pH shows a rise from the duodenum to the terminal ileum in healthy individuals. Our objectives were to compare the pH in the proximal small intestine (SI) (first 60 min of small intestinal transit) lumen of human volunteers and patients with symptomatic constipation; to quantify contractile pressure profiles of the proximal SI, and to assess the relationship between luminally-recorded contractile pressure and small intestinal transit times (SITT) of a non-disintegrating capsule that measures pH and pressure activity (wireless motility capsule). We used previously acquired records from 39 healthy subjects and 41 patients with symptomatic constipation. Mean pH (±SD) of the proximal SI was similar in healthy subjects and patients with constipation at 6.2 (±0.6) and 6.3 (±0.4), respectively. In 13 of the healthy subjects, pH did not rise uniformly in the proximal SI though the pHmedian was 6.0 (5th, 95th percentiles 3.09, 7.06) and the pH fluctuated over a mean period of 28 min. Large inter-individual variability in frequency of pressure activity (Ct) and area under pressure curve (AUC) were 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. Ct and AUC showed a strong direct linear correlation at r = 0.91, p < 1 × 10−6. An inverse correlation (suggesting longer SITT with lower pressure activity) was observed between Ct/AUC and SITT in both healthy subjects and patients with symptomatic constipation. The pooled results for both groups showed: AUC and SITT correlation at r = −0.49, p < 1 × 10−6. We concluded that both the frequency and amplitude of contractions in the proximal SI are important for the propagation of non-disintegrating capsules. The observed pH fluctuations in the proximal SI may impact supersaturation and precipitation of weakly basic drugs.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 158-164 |
| Number of pages | 7 |
| Journal | International Journal of Pharmaceutics |
| Volume | 544 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jun 10 2018 |
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Keywords
- Absorption
- Bioavailability
- Disintegration
- Dissolution
- Enteric
- Modified release
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule. / Aburub, A.; Fischer, Monika; Camilleri, M.; Semler, J. R.; Fadda, H. M.
In: International Journal of Pharmaceutics, Vol. 544, No. 1, 10.06.2018, p. 158-164.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule
AU - Aburub, A.
AU - Fischer, Monika
AU - Camilleri, M.
AU - Semler, J. R.
AU - Fadda, H. M.
PY - 2018/6/10
Y1 - 2018/6/10
N2 - Gastrointestinal luminal pH shows a rise from the duodenum to the terminal ileum in healthy individuals. Our objectives were to compare the pH in the proximal small intestine (SI) (first 60 min of small intestinal transit) lumen of human volunteers and patients with symptomatic constipation; to quantify contractile pressure profiles of the proximal SI, and to assess the relationship between luminally-recorded contractile pressure and small intestinal transit times (SITT) of a non-disintegrating capsule that measures pH and pressure activity (wireless motility capsule). We used previously acquired records from 39 healthy subjects and 41 patients with symptomatic constipation. Mean pH (±SD) of the proximal SI was similar in healthy subjects and patients with constipation at 6.2 (±0.6) and 6.3 (±0.4), respectively. In 13 of the healthy subjects, pH did not rise uniformly in the proximal SI though the pHmedian was 6.0 (5th, 95th percentiles 3.09, 7.06) and the pH fluctuated over a mean period of 28 min. Large inter-individual variability in frequency of pressure activity (Ct) and area under pressure curve (AUC) were 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. Ct and AUC showed a strong direct linear correlation at r = 0.91, p < 1 × 10−6. An inverse correlation (suggesting longer SITT with lower pressure activity) was observed between Ct/AUC and SITT in both healthy subjects and patients with symptomatic constipation. The pooled results for both groups showed: AUC and SITT correlation at r = −0.49, p < 1 × 10−6. We concluded that both the frequency and amplitude of contractions in the proximal SI are important for the propagation of non-disintegrating capsules. The observed pH fluctuations in the proximal SI may impact supersaturation and precipitation of weakly basic drugs.
AB - Gastrointestinal luminal pH shows a rise from the duodenum to the terminal ileum in healthy individuals. Our objectives were to compare the pH in the proximal small intestine (SI) (first 60 min of small intestinal transit) lumen of human volunteers and patients with symptomatic constipation; to quantify contractile pressure profiles of the proximal SI, and to assess the relationship between luminally-recorded contractile pressure and small intestinal transit times (SITT) of a non-disintegrating capsule that measures pH and pressure activity (wireless motility capsule). We used previously acquired records from 39 healthy subjects and 41 patients with symptomatic constipation. Mean pH (±SD) of the proximal SI was similar in healthy subjects and patients with constipation at 6.2 (±0.6) and 6.3 (±0.4), respectively. In 13 of the healthy subjects, pH did not rise uniformly in the proximal SI though the pHmedian was 6.0 (5th, 95th percentiles 3.09, 7.06) and the pH fluctuated over a mean period of 28 min. Large inter-individual variability in frequency of pressure activity (Ct) and area under pressure curve (AUC) were 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. Ct and AUC showed a strong direct linear correlation at r = 0.91, p < 1 × 10−6. An inverse correlation (suggesting longer SITT with lower pressure activity) was observed between Ct/AUC and SITT in both healthy subjects and patients with symptomatic constipation. The pooled results for both groups showed: AUC and SITT correlation at r = −0.49, p < 1 × 10−6. We concluded that both the frequency and amplitude of contractions in the proximal SI are important for the propagation of non-disintegrating capsules. The observed pH fluctuations in the proximal SI may impact supersaturation and precipitation of weakly basic drugs.
KW - Absorption
KW - Bioavailability
KW - Disintegration
KW - Dissolution
KW - Enteric
KW - Modified release
UR - http://www.scopus.com/inward/record.url?scp=85046151704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046151704&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2018.04.031
DO - 10.1016/j.ijpharm.2018.04.031
M3 - Article
C2 - 29678546
AN - SCOPUS:85046151704
VL - 544
SP - 158
EP - 164
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -