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

• Published in: International journal of pharmaceutics 2023-03, Vol.634, p.122645-122645, Article 122645
• Main Authors: Huang, Qiang, Zou, Zhiren, Li, Xiaobo, Xiao, Qinwen, Liang, Guang, Wu, Wenqi
• Format: Article
• Language: English
• Subjects: Amino Acids - chemistry; Amorphous solid dispersions; Dissolution; Drug Liberation; Drug Stability; Lysine - chemistry; Physical stability; Poly (amino acid)s; Poorly water-soluble drugs; Solubility; Water
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.122645

[Display omitted] 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.