scholarly journals Importance of the Unstirred Water Layer and Hepatocyte Membrane Integrity In Vitro for Quantification of Intrinsic Metabolic Clearance

2017 ◽  
Vol 46 (3) ◽  
pp. 268-278 ◽  
Author(s):  
Francesca L. Wood ◽  
J. Brian Houston ◽  
David Hallifax
Keyword(s):  
Membrane Integrity ◽  
Water Layer ◽  
Metabolic Clearance ◽  
Unstirred Water Layer

scholarly journals Unstirred Water Layer Effects on Biodegradable Microspheres

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Susan D’Souza ◽  
Jabar A. Faraj ◽  
Patrick P. DeLuca
Keyword(s):  
Drug Release ◽  
Mass Loss ◽  
Polymer Degradation ◽  
Water Layer ◽  
Biodegradable Microspheres ◽  
Release Process ◽  
Unstirred Water Layer ◽  
Fourfold Increase ◽  
Static Conditions

This study explores the mechanistic aspects of in vitro release from biodegradable microspheres with the objective of understanding the effect of the unstirred water layer on polymer degradation and drug release. In vitro drug release experiments on Leuprolide PLGA microspheres were performed under “static” and “continuous” agitation conditions using the “sample and separate” method. At specified time intervals, polymer degradation, mass loss, and drug release were assessed. While molecular weight and molecular number profiles for “static” and “continuous” samples were indistinct, mass loss occurred at a faster rate in “continuous” samples than under “static” conditions. In vitro results describe a fourfold difference in drug release rates between the “continuous” and “static” samples, ascribed to the acceleration of various processes governing release, including elimination of the boundary layer. The findings were confirmed by the fourfold increase in drug release rate when “static” samples were subjected to “continuous” agitation after 11 days. A schema was proposed to describe the complex in vitro release process from biodegradable polymer-drug dosage forms. These experiments highlight the manner in which the unstirred water layer influences drug release from biodegradable microspheres and stress the importance of selecting appropriate conditions for agitation during an in vitro release study.

scholarly journals Studies on drug absorption from oral cavity. II Influence of the unstirred water layer on absorption from hamster cheek pouch in vitro and in vivo.

1987 ◽  
Vol 10 (4) ◽  
pp. 180-187 ◽  
Author(s):  
YUJI KUROSAKI ◽  
SHINICHI HISAICHI ◽  
CHIEKO HAMADA ◽  
TAIJI NAKAYAMA ◽  
TOSHIKIRO KIMURA
Keyword(s):  
Oral Cavity ◽  
Drug Absorption ◽  
Water Layer ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Unstirred Water Layer

Jejunal uptake of sugars, cholesterol, fatty acids, and fatty alcohols in vivo in diabetic rats

1985 ◽  
Vol 63 (11) ◽  
pp. 1356-1361
Author(s):  
C. Hotke ◽  
Y. McIntyre ◽  
A. B. R. Thomson
Keyword(s):  
Fatty Acids ◽  
Lauric Acid ◽  
Water Layer ◽  
Diabetic Rats ◽  
The Body ◽  
Unstirred Layer ◽  
Unstirred Water Layer ◽  
Uptake Of Nutrients

Previous in vitro studies have demonstrated enhanced active and passive intestinal uptake of nutrients in streptozotocin-diabetic rats, but the effect of diabetes on the in vivo absorption of glucose and amino acids remains controversial, and the effect of diabetes on the in vivo uptake of lipids has not been reported. Accordingly, an in vivo perfusion technique was used in rats to examine the uptake of nutrients from the intestinal lumen, their transfer to the body, their mucosal and submucosal content, and the percentage of uptake transferred. Diabetes was associated with reduced uptake of fatty alcohols, indicating that the effective resistance of the unstirred water layer in vivo is higher in diabetic than in nondiabetic control rats. The mucosal and submucosal content of dodecanol was lower in diabetic than in control rats, but the percentage of the dodecanol uptake transferred to the body was higher. Although the uptake of varying concentrations of D-galactose was similar in diabetic and in control animals, kinetic analysis corrected for unstirred layer effects demonstrated lower mean values of the passive permeability coefficients (Pd) for galactose in diabetic than in control animals, with lower values of the Michaelis constant (Km) and higher values of the maximal transport rate [Formula: see text]. The uptake of lauric acid was reduced in diabetic rats, whereas the uptake of deconoic acid and of cholesterol was unchanged. With correction for unstirred layer effects, it was apparent that the jejunum of diabetic rats was in fact more permeable to decanoic and lauric acid as well as to cholesterol. The results suggest that (i) in diabetic rats the effective resistance of the unstirred water layer between the jejunal lumen and the brush border membrane is lower; (ii) the differences in unstirred layer resistance between the diabetic and control animals obscure the changes in the kinetic constants (Pd, Km, [Formula: see text]) describing the uptake of galactose, medium chain length fatty acids and cholesterol; and (iii) the kinetic changes in nutrient uptake observed in vitro may be confirmed in vivo once the effect of intestinal unstirred layers has been taken into account.

scholarly journals Intestinal absorption of linoleic acid in experimental renal failure

1991 ◽  
Vol 66 (3) ◽  
pp. 467-477
Author(s):  
M. V. Pahl ◽  
A. Barbari ◽  
N. D. Vaziri ◽  
D. Hollander ◽  
M. Yazdani ◽  
...  
Keyword(s):  
Renal Failure ◽  
Linoleic Acid ◽  
Water Layer ◽  
Short Term ◽  
Unstirred Water Layer ◽  
Wide Range ◽  
Significant Difference

Linoleic acid (LA) transport in rats with experimental short-term and long-term renal failure (RF) was compared with that of sham-operated normal animals on liberal food intake and pair-fed animals. The perfusions in vivo and incubations in vitro were conducted using a micellar solution containing a wide range of LA concentrations. Both absorption in vivo and uptake in vitro of LA were significantly reduced in animals with short-term RF. Lipid extraction and separation by thin-layer chromatography revealed a marked LA trapping as trilinolein (TL) in the perfused intestinal tissue in the short-term RF group. The esterification process, as defined by the rate of LA incorporation into TL, was moderately reduced in short-term RF animals. The thickness of the unstirred water layer showed no significant difference among the groups studied. In contrast, animals with long-term RF exhibited normal absorption of LA in vivo at all concentrations tested. In conclusion, LA absorption is reduced in short-term RF and restored in long-term RF. Several steps including LA transport into and TL transport out of the enterocyte and the esterification process were impaired in short-term RF. These changes are not due to alteration in the unstirred water layer, anorexia, weight loss or a rapid effect of uraemic chemical environment or circulatory factors.

Uptake of cholesterol into rabbit jejunum using three in vitro techniques: importance of bile acid micelles and unstirred layer resistance

1981 ◽  
Vol 241 (3) ◽  
pp. G270-G274
Author(s):  
A. B. Thomson ◽  
B. D. O'Brien
Keyword(s):  
Bile Acid ◽  
Water Layer ◽  
Effective Resistance ◽  
Bulk Phase ◽  
Unstirred Layer ◽  
Cholesterol Concentration ◽  
Unstirred Water Layer ◽  
In Vitro Techniques ◽  
Rabbit Jejunum

The rate of uptake (Jd) of cholesterol into the intestine is influenced by the effective resistance of the unstirred water layer, the concentration of the probe molecule at the aqueous-membrane interface, and the passive permeability characteristics of the membrane. This study was undertaken to determine the influence of the bile acid micelle and the unstirred water layer on the Jd of cholesterol into rabbit jejunum, using everted sacs, full-thickness biopsies, and disks. When the bulk phase was stirred and the resistance of the unstirred layer was low, there was a linear relation between cholesterol concentration in the bulk phase and Jd when the concentration of taurodeoxycholic acid (TDC) was constant, but increasing TDC in the presence of a constant concentration of cholesterol was associated with a decline in Jd. When the concentration of both TDC and cholesterol was varied but the ratio of TDC to cholesterol was maintained constant, Jd increased slightly. The Jd of cholesterol was higher into sacs than into biopsies, which in turn was greater than into disks; Jd into disks was much lower when the resistance of the unstirred layer was high. These results suggest that 1) the bile acid micelle serves to provide a reservoir for partitioning of the cholesterol from the micelle into the aqueous phase from which the cholesterol is absorbed; 2) the Jd of cholesterol into disks of jejunum is influenced by the effective resistance of the unstirred water layer; and 3) although the quantity of cholesterol Jd varies markedly between sacs, biopsies, and disks, the qualitative aspects of the role of the bile acid micelle in cholesterol absorption were similar using the different in vitro techniques.

Unstirred water layer and age-dependent changes in rabbit jejunal D-glucose transport.

1979 ◽  
Vol 236 (6) ◽  
pp. E685
Author(s):  
A B Thomson
Keyword(s):  
Glucose Transport ◽  
Water Layer ◽  
Affinity Constant ◽  
Mucosal Cell ◽  
Unstirred Water Layer ◽  
Age Related ◽  
Microvillus Membrane ◽  
High Concentrations ◽  
High Doses

The unidirectional flux of solutes into the intestinal mucosal cell is determined by passage through the microvillus membrane and the overlying unstirred water layer, UWL. An in vitro technique was employed to determine the effect of the UWL on glucose transport into the jejunum of suckling, mature, and old rabbits. When the resistance of UWL was high, the uptake from high concentrations of glucose increased as the animals grew older; this change with aging was not seen from low concentrations of glucose. When UWL resistance was minimized by stirring the bulk phase, similar amounts of glucose were absorbed from high doses, but uptake from low doses was greater in young than in old animals. Studies undertaken to determine the kinetic basis of these age-related changes showed that with increasing age i) the apparent passive permeability coefficient P of glucose fell, ii) the maximum transport rate Jdmax rose, and iii) the apparent affinity constant Km increased. These differences were not observed when the resistance of the UWL was high: P and Km were similar in suckling, mature, and old animals, and the increase in glucose uptake with age was due to the greater Jdmax. Thus the potential benefit of the high affinity, high permeability transport system of young animals may be obscured by high resistance of the UWL.

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