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

[Display omitted] 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 pro...

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Bibliographic Details
Published in:	International journal of pharmaceutics 2020-08, Vol.586, p.119545-119545, Article 119545
Main Authors:	Tian, Yiwei, Jacobs, Esther, Jones, David S., McCoy, Colin P., Wu, Han, Andrews, Gavin P.
Format:	Article
Language:	eng
Subjects:	Amorphous Amorphous solid dispersion Chemistry, Pharmaceutical Drug Carriers - chemistry Drug Stability Drug Storage Excipients - chemistry Flory-Huggins Hot-melt extrusion Humidity Ibuprofen - administration & dosage Ibuprofen - chemistry Indomethacin - administration & dosage Indomethacin - chemistry Naproxen - administration & dosage Naproxen - chemistry Polymers - chemistry Polymethacrylic Acids - chemistry Small angle X-ray scattering Solubility Thermodynamic phase diagram Thermodynamics
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Summary:	[Display omitted] 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.
ISSN:	0378-5173 1873-3476