Dissolution changes in drug-amino acid/biotin co-amorphous systems: Decreased/increased dissolution during storage without recrystallization.

Co-amorphous systems have been proven to be a promising strategy to address the poor water solubility of poorly water-soluble drugs. Generally, the initial dissolution behaviors after co-amorphous system preparation and the potential recrystallization during storage are used to evaluate the performance of co-amorphous systems. However, this study reveals that decreased dissolution and unexpected increased dissolution were observed during storage though the co-amorphous systems maintained amorphous form. Three drugs (valsartan, tadalafil, mebendazole) and three co-formers (arginine, tryptophan, biotin) were used to prepare co-amorphous systems and the samples were stored for different times. After stored for 80 d, most of the co-amorphous systems maintained amorphous form, however, decreased and increased intrinsic dissolution rates (IDRs) were both observed in these non-recrystallized co-amorphous systems. The moisture changes of the systems during storage and the possible drug-co-former molecular interactions showed no effect on the dissolution changes, while phase separation might play a role in it. In conclusion, more attention should be paid to the dissolution changes of co-amorphous systems during storage. Focusing on the initial dissolution behaviors after sample preparation and the physical recrystallization during storage is not enough for the development of co-amorphous systems in future.

Poly (amino acid)s as new co-formers in amorphous solid dispersion.

The drug-amino acid co-amorphous systems and amorphous solid dispersions (ASDs) are promising methods to address the poor water solubility of poorly water-soluble drugs. However, some amino acids might not be perfect co-formers for co-amorphous systems, and the relatively low drug-loading of many ASDs is one of the main disadvantages of ASDs. Thus, poly-l-lysine and polyglutamic acid were selected as the co-formers, ball milled with basic mebendazole, neutral tadalafil and acidic valsartan at different weight ratios (from 3:1 to 1:3) to prepare poly (amino acid)-based ASDs, aiming to combine the advantages of co-amorphous systems (high drug-loading) and ASDs (relatively high Tg and high physical stability). All the mixtures were converted into amorphous after milling. The powder dissolution studies showed that drug-poly (amino acid) ASDs improved the dissolution rate of the drug in different ways and to different degrees. Moreover, the two poly (amino acid)s enhanced the physical stability of amorphous drugs. It is worthy to mention that the salt formation between the drug and the poly (amino acid) does not necessarily mean better performance compared to non-salt forming systems, and salt formation is also not a prerequisite for the formation of promising drug-poly (amino acid) ASDs.