Back to Search Start Over

The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform.

Authors :
Tian Y
Jacobs E
Jones DS
McCoy CP
Wu H
Andrews GP
Source :
International journal of pharmaceutics [Int J Pharm] 2020 Aug 30; Vol. 586, pp. 119545. Date of Electronic Publication: 2020 Jun 14.
Publication Year :
2020

Abstract

Amorphous solid dispersion (ASD) is a formulation strategy extensively used to enhance the bioavailability of poorly water soluble drugs. Despite this, they are limited by various factors such as limited drug loading, poor stability, drug-excipient miscibility and the choice of process platforms. In this work, we have developed a strategy for the manufacture of high drug loaded ASD (HDASD) using hot-melt extrusion (HME) based platform. Three drug-polymer combinations, indomethacin-Eudragit®E, naproxen-Eudragit®E and ibuprofen-Eudragit®E, were used as the model systems. The design spaces were predicted through Flory-Huggins based theory, and the selected HDASDs at pre-defined conditions were manufactured using HME and quench-cooled melt methods. These HDASD systems were also extensively characterised via small angle/wide angle x-ray scattering, differential scanning calorimetry, Infrared and Raman spectroscopy and atomic force microscopy. It was verified that HDASDs were successfully produced via HME platform at the pre-defined conditions, with maximum drug loadings of 0.65, 0.70 and 0.60 w/w for drug indomethacin, ibuprofen and naproxen respectively. Enhanced physical stability was further confirmed by high humidity (95%RH) storage stability studies. Through this work, we have demonstrated that by the implementation of predictive thermodynamic modelling, HDASD formulation design can be integrated into the HME process design to ensure the desired quality of the final dosage form.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1873-3476
Volume :
586
Database :
MEDLINE
Journal :
International journal of pharmaceutics
Publication Type :
Academic Journal
Accession number :
32553496
Full Text :
https://doi.org/10.1016/j.ijpharm.2020.119545