Further exploring the pharmaceutical applications of novel microwave-induced in situ amorphization

Microwave-induced in situ amorphization is an emerging solubilizing technology to tackle the persistent physical stability and problematic downstream processing issues of amorphous solid dispersions (ASDs). However, the current available research in this field is limited and some issues identified in the existing studies require further exploration. The aims of this study were to fill in these gaps by: 1) systematically exploring the mechanisms of microwave-induced in situ amorphization, 2) investigating novel microwave-able systems with improved practicality in the pharmaceutical area, and 3) further assessing the final performance of the completely amorphized microwaved formulations. Physically mixed compacts composed of indomethacin (IND, the model drug), dielectric excipients and polymeric carriers were prepared, microwaved and characterized to study the amorphization efficiency and the physical stability. The ability of dielectric excipients in facilitating microwave-induced in situ amorphization was assessed by comparing the IND amorphicity, amorphization rate, and systemic homogeneity. The chemical stability and the in vitro dissolution performance of compacts were also analyzed. Results showed that microwave-able compacts composed of moisture, moisture substitutes, and non-ionic surfactants could all be successfully developed, which also demonstrated the functions of such dielectric excipients as microwave absorbers, plasticizers, and/or solubilizers. The microwave-induced ASDs in the three systems all presented good in vitro dissolution performance, robust short-term physical stability and chemical stability. The range of effective carriers and dielectric excipients for microwave-induced in situ amorphization was greatly expanded. The influencing factors associated with the systemic molecular mobility and the temperature threshold of amorphization were suggested to have significant impacts on the amorphization rate of IND. The occurrence of the dissolution-mediated in situ amorphization was investigated in depth, providing a better understanding of the mechanisms of microwave-induced in situ amorphization. Overall, the current study has revealed a great potential in pharmaceutical applications of microwave-induced in situ amorphization.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2022

Author dc:creator

• Qiang, Wei

Advisors dc:contributor.advisor

• McCoy, Colin
• Andrews, Gavin

• Amorphous solid dispersions
• microwave-induced in situ amorphization
• polymers
• moisture
• surfactant
• dissolution

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/8d40d4b9-416a-43c6-a5f6-c1fd77f25d22

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/8d40d4b9-416a-43c6-a5f6-c1fd77f25d22