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- Dahlgren, David, et al.
(författare)
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Regional Intestinal Permeability in Dogs : Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3022-3033
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Tidskriftsartikel (refereegranskat)abstract
- The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine. Dogs are commonly used in preclinical evaluation of regional intestinal absorption and in the development of novel MR dosage forms. This study determined regional intestinal effective permeability (P-eff) in dogs with the aim to improve regional Peff prediction in humans. Four model drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and regionally dosed twice as a solution into the proximal small intestine (P-SI) and large intestine (LI) of three dogs with intestinal stomas. Based on plasma data from two separate study occasions for each dog, regional Peff values were calculated using a validated intestinal deconvolution method. The determined mean P-eff values were 0.62, 0.14, 1.06, and 3.66 X 10(-4) cm/s in the P-SI, and 0.13, 0.02, 1.03, and 2.20 X 10(-4) cm/s in the LI, for atenolol, enalaprilat, metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog were highly correlated (R-2 = 0.98) to the historically directly determined human jejunal P-eff after a single-pass perfusion. The determined dog P-SI P-eff values were also successfully implemented in GI-Sim to predict the risk for overestimation of LI absorption of low permeability drugs. We conclude that the dog intestinal stoma model is a useful preclinical tool for determination of regional intestinal permeability. Still, further studies are recommended to evaluate additional APIs, sources of variability, and formulation types, for more accurate determination of the dog model in the drug development process.
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| 2. |
- Hu, Min, 1979-, et al.
(författare)
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Comparison of local variation of modulus of elasticity determined on basis of scanned fiber angles and full strain field measurements
- 2013
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Ingår i: The 18th International Nondestructive Testing and Evaluation of Wood Symposium. - Madison, WI, USA.
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Konferensbidrag (refereegranskat)abstract
- Strength grading methods are normally based on relationships between one measured value of modulus of elasticity (MOE), regarded as being valid for the whole board, and bending strength. Studies have shown, however, that with a detailed knowledge of local variation of MOE within boards, a highter coefficient of determination (R2) with respect to bending strength can be obtained. Measurements of fiber angles from laser scanning has shown to be a powerful tool to establish MOE profile along boards in a speed that cooresponds to the production speed at a sawmill. The present study aims at investigating the accuracy of the local MOE profile determined on basis of fiber angles from laser scanning. The study was carried out on a board of Norway spruce of dimension 50 by 150 by 3,900 mm. First the fiber angles on all four surfaces were identified using a WoodEye scanner and on the basis of these measurements, a MOE profile was calculated. Thereafter, the board was subjected to a constant bending moment and suring loading an image correlation system, Aramis, was employed for detection of the strain field with high resolution along the whole board. This strain field was then used to estanlish a 'true' MOE profile along the board. The MOE profiles determined in two different ways were compared and they show a close compliance. However, some difference were found and these were used for calibration of the method for MOE determination on the basis of scanning results. The present research thus contributes further improvement of a newly suggested grading method.
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