Development of Dexlansoprazole Delayed-Release Capsules, a Dual Delayed-Release Proton Pump Inhibitor.

Autor:	Grady H; Department of Pharmaceutical Sciences, Takeda Pharmaceuticals International, 40 Lansdowne Street, Cambridge, Massachusetts 02139. Electronic address: haiyan.grady@takeda.com., Murakawa Y; Department of Pharmaceutical Sciences, Takeda Pharmaceuticals International, 40 Lansdowne Street, Cambridge, Massachusetts 02139., Mulford D; Department of Clinical Pharmacology, Takeda Research and Development, One Takeda Parkway, Deerfield, Illinois 60015., Kukulka M; Department of Clinical Pharmacology, Takeda Research and Development, One Takeda Parkway, Deerfield, Illinois 60015.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2019 Nov; Vol. 108 (11), pp. 3496-3501. Date of Electronic Publication: 2019 Aug 03.
DOI:	10.1016/j.xphs.2019.07.023
Abstrakt:	Proton pump inhibitors (PPIs) are widely used for treating acid-related disorders. For an "ideal PPI," achieving maximal absorption and sustaining pharmacodynamic effects through the 24-h dosing cycle are critical features. Dexlansoprazole offers a relevant case study on how an improved PPI was developed capitalizing on the rational optimization of a precursor molecule-in this case, using lansoprazole as a starting point, leveraging its chemical properties on pharmacokinetics, and exploring optimized formulations. Dexlansoprazole is the R(+)-enantiomer of lansoprazole and shows stereoselective differences in absorption and metabolism compared with the racemic mixture of lansoprazole. The formulation was further refined to use pulsate-type granules with enteric coating to withstand acidic gastric conditions, while allowing prolonged absorption in the proximal and distal small intestine. As a result, the dual delayed-release formulation of dexlansoprazole has a plasma concentration-time profile characterized by 2 distinct peaks, leading to an extended duration of therapeutic plasma drug concentrations compared with the conventional delayed-release lansoprazole formulation. The dual delayed-release formulation maintains plasma drug concentrations longer than the lansoprazole delayed-release formulation at all doses. (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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