Development of novel prasugrel base microsphere-loaded tablet with enhanced stability: Physicochemical characterization and in vivoevaluation in beagle dogs

Title
Development of novel prasugrel base microsphere-loaded tablet with enhanced stability: Physicochemical characterization and in vivoevaluation in beagle dogs
Author
김경수
Keywords
Prasugrel base; Microsphere; Phosphoric acid; Stability; Solubility; Bioavailability; Bioequivalence; THIENOPYRIDINE ANTIPLATELET AGENT; CORONARY-ARTERY-DISEASE; SPRAY-DRYING TECHNIQUE; SODIUM LAURYL SULFATE; DRUG-DELIVERY SYSTEMS; SOLID-DISPERSION; ORAL BIOAVAILABILITY; CLOPIDOGREL NAPADISILATE; PLATELET-AGGREGATION; CRYSTALLINE CHANGE
Issue Date
2016-10
Publisher
Elsevier
Citation
Colloids and Surfaces B: Biointerfaces, v. 146, Page. 754-761
Abstract
The objective of this study was to develop a novel prasugrel base microsphere-loaded tablet (PBMST) with enhanced stability as a bioequivalent to the commercial prasugrel hydrochloride-loaded tablet. Numerous prasugrel base-loaded microspheres were prepared with hydroxypropylmethyl cellulose (HPMC), colloidal silica and various acidifying agents using a spray-drying process, and the physicochemical properties, solubility and stability were investigated. The PBMSTs were prepared and their dissolution, pharmacokinetics in beagle dogs and stability were evaluated compared to commercial prasugrel hydrochloride-loaded tablets. Among the acidifying agents tested, phosphoric acid provided the greatest increase in drug solubility, by as much as 110-fold. The prasugrel base-loaded microspheres composed of prasugrel base, HPMC, colloidal silica and phosphoric acid at a weight ratio of 10/10/5/2.5 provided an amorphous drug and reduced particle size of about 11.3 mu m. Moreover, it exhibited excellent solubility and improved stability compared to prasugrel base and hydrochloride. Moreover, PBMST drug dissolution was improved in comparison to the prasugrel base-loaded tablet (PBT), with similar dissolution to the commercial prasugrel hydrochloride-loaded tablet at pH 1.2 and 4.0. PBMST provided significantly higher plasma concentrations of AUC and Cinax in beagle dogs compared to PBT. In particular, the AUC of PBMST was approximately four times greater than PBT, leading to improved oral bioavailability. There were no significant differences observed for all pharmacokinetic parameters between PBMST and the commercial prasugrel hydrochloride-loaded tablet, suggesting their bioequivalence in beagle dogs. Furthermore, the prepared PBMSTs were stable for at least six months. Therefore, this novel prasugrel base microsphere-loaded tablet could be a potential alternative for enhancing the stability and bioavailability of prasugrel. (C) 2016 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0927776516305276http://repository.hanyang.ac.kr/handle/20.500.11754/70371
ISSN
0927-7765; 1873-4367
DOI
10.1016/j.colsurfb.2016.07.025
Appears in Collections:
RESEARCH INSTITUTE[E](부설연구소) > INSTITUTE OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY(약학기술연구소) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE