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Mitigating unwanted amorphisation: A screening method for the selection of suitable excipients.
Youness Amharar1, Vincent Curtin1, Kieran H Gallagher1
1School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Summary
A new screening method effectively selects excipients to prevent drug amorphisation during milling. This method uses excipient glass transition temperature (Tg) and drug solubility to identify optimal additives for stable amorphous drug formulations.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Physical Chemistry
Background:
- Co-processing active pharmaceutical ingredients (APIs) with low glass transition temperature (Tg) excipients prevents drug amorphisation during milling.
- This strategy relies on excipient-API molecular dispersion, reducing Tg and promoting recrystallization.
Purpose of the Study:
- Develop a screening method to select suitable excipients for preventing API amorphisation.
- Evaluate excipient Tg and solubility in amorphous APIs as key selection criteria.
Main Methods:
- Assessed excipient-induced Tg reduction using thermal analysis of amorphous composites.
- Calculated excipient solubility in amorphous APIs via Hildebrand solubility parameters.
- Validated screening predictions against experimental milling results for griseofulvin and budesonide.
Main Results:
- The developed screening method showed good agreement with experimental outcomes for both APIs.
- Identified excipient Tg and API's capacity for amorphous molecular dispersion as critical parameters.
- Confirmed the efficacy of low Tg excipients and introduced polymeric additives for amorphisation mitigation.
Conclusions:
- The screening method efficiently identifies appropriate excipients to prevent API amorphisation.
- Excipient Tg and API-excipient solubility are crucial for forming stable amorphous molecular dispersions.
- This study validates and extends previous findings on using low Tg excipients for milling stabilization.
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