Relationship between amorphous solid dispersion in vivo absorption and in vitro dissolution: phase behavior during dissolution, speciation, and membrane mass transport

2018 ◽  
Vol 292 ◽  
pp. 172-182 ◽  
Author(s):  
Venecia Wilson ◽  
Xiaochun Lou ◽  
Donald J. Osterling ◽  
Deanne F. Stolarik ◽  
Gary Jenkins ◽  
...  
Keyword(s):  
Mass Transport ◽  
Phase Behavior ◽  
Solid Dispersion ◽  
Amorphous Solid ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
In Vivo Absorption

Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier

2017 ◽  
Vol 531 (1) ◽  
pp. 324-331 ◽  
Author(s):  
Johan Wendelboe ◽  
Matthias Manne Knopp ◽  
Fauzan Khan ◽  
Nabil Chourak ◽  
Thomas Rades ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Ph Sensitive ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion

scholarly journals Amorphous solid dispersions and the confounding effect of nanoparticles in in vitro dissolution and in vivo testing: Niclosamide as a case of study

2020 ◽  
Author(s):  
Miguel O Jara ◽  
Zachary N Warnken ◽  
Robert O Williams
Keyword(s):  
Amorphous Solid ◽  
Fold Increase ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
In Vitro Tests ◽  
Manufacturing Method ◽  
Poorly Water Soluble

We developed an amorphous solid dispersion (ASD) of the poorly water soluble molecule niclosamide that achieved more than a 2 fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60 fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, BCS class II, and a poor glass former with low bioavailability in vivo. Hot melt extrusion is a high throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer polyvinylpyrrolidone vinyl acetate (PVPVA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using DSC, XRD, NMR, FTIR, and DLS. The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side by side diffusion test, these nanoparticles produced a 4 fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

scholarly journals Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 235 ◽  
Author(s):  
Lyes Mehenni ◽  
Malika Lahiani-Skiba ◽  
Guy Ladam ◽  
François Hallouard ◽  
Mohamed Skiba
Keyword(s):  
Amphotericin B ◽  
Solid Dispersion ◽  
In Vitro Release ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
New Generation ◽  
Powder Aerosols

In the present study, new polymer microspheres of amphotericin B (AmB) were prepared by a spray drying technique using cyclodextrin polymers (Poly-CD) to improve the solubility and dissolution of AmB, to prevent in vivo toxic AmB aggregations. Formulations were characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermal analysis, Raman spectroscopy, particle size, drug purity test and in vitro release studies. The analysis indicated that the chemical structure of AmB remained unchanged in the amorphous solid dispersion, but the structure was changed from crystalline to amorphous. AmB was completely release from such optimized formulations in dissolution media in 40 min. This work may contribute to a new generation of spherical amorphous solid dispersion using a cyclodextrin polymer, which has implications for the possibility of drug development for oral utilization or as powder aerosols for pulmonary administration.

Generation of a Weakly Acidic Amorphous Solid Dispersion of the Weak Base Ritonavir with Equivalent In Vitro and In Vivo Performance to Norvir Tablet

2018 ◽  
Vol 19 (5) ◽  
pp. 1985-1997 ◽  
Author(s):  
Daniel J. Ellenberger ◽  
Dave A. Miller ◽  
Sandra U. Kucera ◽  
Robert O. Williams
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Weak Base

In vitro and in vivo characterization on amorphous solid dispersion of cyclosporine A for inhalation therapy

2009 ◽  
Vol 138 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Satomi Onoue ◽  
Hideyuki Sato ◽  
Yohei Kawabata ◽  
Takahiro Mizumoto ◽  
Naofumi Hashimoto ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Cyclosporine A ◽  
Amorphous Solid ◽  
Inhalation Therapy ◽  
Amorphous Solid Dispersion ◽  
In Vivo Characterization

Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism

2019 ◽  
Vol 16 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Ting Wen ◽  
Boyi Niu ◽  
Qiaoli Wu ◽  
Yixian Zhou ◽  
Xin Pan ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Dissolution Test ◽  
Melt Extrusion ◽  
Cell Transport ◽  
Hot Melt

Background: Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. Objective: The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. Methods: The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. Results: The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). Conclusion: In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.

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