Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole

Content Provider	Scilit
Author	Vialpando, Monica Smulders, Stefanie Bone, Scott Jager, Casey Vodak, David Speybroeck, Michiel Van Verheyen, Loes Backx, Katrien Boeykens, Peter Brewster, Marcus E. Ceulemans, Jens de Armas, Hector Novoa Geel, Katrien Van Kesselaers, Emma Hillewaert, Vera Lachau-Durand, Sophie Meurs, Greet Psathas, Petros Hove, Ben Van Verreck, Geert Voets, Marieke Weuts, Ilse Mackie, Claire
Copyright Year	2016
Description	Journal: Journal of Pharmaceutical Sciences This study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH. All formulations remained amorphous at 25°C/60% RH. Only the MPSDD formulation containing HPMCAS-M and 3/7 (wt./wt.) FLU/OMS did not crystallize following 40°C/75% RH exposure. The OMS and MPSDD formulations contained the lowest and highest amount of hydrolyzed degradant, respectively. All formulations were dosed to rats at 20 mg/kg in suspension. One FLU/OMS formulation was also dosed as a capsule blend. Plasma concentration profiles were determined following a single dose. In vivo findings show that the OMS capsule and suspension resulted in the overall highest area under the curve and $C_{max}$ values, respectively. These results cross-evaluate various amorphous formulations and provide a link to enhanced biopharmaceutical performance.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988473/pdf https://core.ac.uk/download/pdf/82797019.pdf http://jpharmsci.org/article/S0022354916004044/pdf
Ending Page	2793
Page Count	12
Starting Page	2782
ISSN	00223549
e-ISSN	15206017
DOI	10.1016/j.xphs.2016.03.003
Journal	Journal of Pharmaceutical Sciences
Issue Number	9
Volume Number	105
Language	English
Publisher	Elsevier BV
Publisher Date	2016-04-21
Access Restriction	Open
Subject Keyword	Journal: Journal of Pharmaceutical Sciences Pharmacology and Pharmacy Poorly Water Soluble Drugs Ordered Mesoporous Silica Active Pharmaceutical Ingredient Area Under the Curve Maximum Drug Concentration
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science