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Dissolution changes in drug-amino acid/biotin co-amorphous systems: Decreased/increased dissolution during storage
Zhiren Zou1, Qiang Huang1, Xiaobo Li1
1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China; Wenzhou Institute, University of Chinese Academy of Science, Wenzhou 325024, Zhejiang, China.
Summary
Co-amorphous systems can improve drug solubility. However, even without recrystallization, their dissolution rates can change unpredictably during storage, impacting drug development.
Area of Science:
- Pharmaceutical Science
- Materials Science
Background:
- Co-amorphous systems enhance the solubility of poorly water-soluble drugs.
- Current evaluations focus on initial dissolution and recrystallization during storage.
Purpose of the Study:
- To investigate dissolution rate changes in co-amorphous systems during storage.
- To explore factors influencing these changes beyond recrystallization.
Main Methods:
- Prepared co-amorphous systems using three drugs (valsartan, tadalafil, mebendazole) and three co-formers (arginine, tryptophan, biotin).
- Stored systems for varying durations (up to 80 days).
- Assessed amorphous form, dissolution rates (intrinsic dissolution rates - IDRs), moisture content, and molecular interactions.
Main Results:
- Most co-amorphous systems remained amorphous after 80 days of storage.
- Both decreased and increased IDRs were observed in non-recrystallized systems.
- Moisture changes and drug-co-former interactions did not correlate with dissolution changes; phase separation may be involved.
Conclusions:
- Dissolution rate changes during storage are critical for co-amorphous systems.
- Evaluating only initial dissolution and physical recrystallization is insufficient for development.
- Further research into factors like phase separation influencing dissolution stability is needed.
Keywords:
AgingCo-amorphous systemsDissolution increaseIntrinsic dissolution rate (IDR)Physical stabilityPoorly water-soluble drugsMore Related Videos
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