Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor

Title
Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor
Author
김경수
Keywords
HM30181 mesylate salt; Microcapsule; P-glycoprotein inhibitor; Paclitaxel; Solubility; Bioavailability; DRUG-DELIVERY SYSTEM; SOLID DISPERSION; PHYSICOCHEMICAL CHARACTERIZATION; ENHANCED STABILITY; BETA-CYCLODEXTRIN; CANCER-CELLS; BIOAVAILABILITY; NANOPARTICLES; DOCETAXEL; RATS
Issue Date
2016-06
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v. 506, No. 1-2, Page. 93-101
Abstract
The purpose of this study was to develop HM30181 mesylate salt (HM30181M)-loaded microcapsules as a novel P-glycoprotein inhibitor for enhancing the oral absorption of paclitaxel. The effect of various carriers including hydrophilic polymers and solvents on the solubility of HM30181M were evaluated. Among the hydrophilic polymers and solvents tested, HPMC and methylene chloride (and ethanol) provided the highest HM30181M solubility. Numerous HM30181M-loaded microcapsules were prepared with HPMC, silicon dioxide and acidifying agents using a spray-drying technique, and their solubility, dissolution and physicochemical properties were evaluated. Furthermore, a pharmacokinetic study was performed after oral administration of paclitaxel alone, simultaneously with HM30181M powder or HM30181M-loaded microcapsules to rats. Among the acidifying agents investigated, phosphoric acid provided the best improvement in the solubility and dissolution of HM30181M. Moreover, the microcapsule composed of HM30181M, HPMC, silicon dioxide and phosphoric acid at a weight ratio of 3:6:3:2 remarkably enhanced the solubility and dissolution of HM30181M compared with the HM30181M powder alone. The microcapsules were spherical in shape, had a reduced particle size of about 7 mm, and contained HM30181M in an amorphous state. Furthermore, this microcapsule significantly enhanced HM30181M absorption, making it about 1.7-fold faster and 1.6-fold greater after simultaneous administration, leading to about 70- and 2-fold improved oral bioavailability of paclitaxel compared with paclitaxel alone and the simultaneous administration with HM30181M powder, respectively. Thus, this novel microcapsule could be a potential candidate for effective P-glycoprotein inhibition during oral administration of paclitaxel. (c) 2016 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0378517316303180http://hdl.handle.net/20.500.11754/65477
ISSN
0378-5173; 1873-3476
DOI
10.1016/j.ijpharm.2016.04.034
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