Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation

Title
Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation
Author(s)
Srinivasan Shanmugam[Srinivasan Shanmugam]김용일[김용일]김영훈[김영훈]박정희[박정희]임호택[임호택]손영택[손영택]김경수[김경수]용철순김종오최한곤[최한곤]우종수[우종수]
Keywords
NITRIC-OXIDE SYNTHASE; SUSTAINED-RELEASE; UTERINE ARTERY; DRUG-DELIVERY; ENDOMETRIAL RECEPTIVITY; POSTMENOPAUSAL WOMEN; VASCULAR DEVELOPMENT; GROWTH RESTRICTION; FERTILIZATION IVF; EMBRYO-TRANSFER
Issue Date
201406
Publisher
INFORMA HEALTHCARE
Citation
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, v.40, no.6, pp.803 - 812
Abstract
Aim: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS). Methods: Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated. Results: The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 +/- 0.020 g, 98.25 +/- 2.50%, 2.5 +/- 0.08 kg and 9 +/- 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson-Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower C-max (similar to 10 times) and AUC(0-24) (h) (similar to 13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher C-max (similar to 40 times) and AUC(0-24 h) (similar to 20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution. Conclusion: This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.
URI
http://hdl.handle.net/YU.REPOSITORY/31946http://dx.doi.org/10.3109/03639045.2013.788011
ISSN
0363-9045
Appears in Collections:
약학대학 > 약학부 > 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