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Investigating to optimal ratio between drug and co-former in co-amorphous systems
1  Copenhagen University

Abstract:

Most new low molecular weight chemical entities in pharmaceutical developments suffer from a low aqueous solubility, making oral delivery challenging. Despite the numerous formulation efforts that can be investigated, research especially on amorphous drugs and formulations appears to be a useful approach. Whilst few drugs can be converted to an amorphous form on their own, due to a too physical stability, the use of amorphous solid dispersions, i.e. the dissolution of drug molecules into (amorphous) polymers is increasingly used. However, certain shortcoming of these polymers based amorphous solid dispersions, such as a low drug load and a usually high hygroscopicity; still necessitate the investigation of alternative approaches. One such approach is the use of co-amorphous systems, i.e. to combination of initially crystalline low molecular weight drugs and excipients. Usually here a 1:1 molar ratio is used, but this may not be the optimal mixing ratio. In this presentation, work on investigating to optimal ratio between drug and co-former will be presented and critically discussed.

Keywords: amorphous; co-amorphous; poor water solubility
Comments on this paper
Andrea Erxleben
Many thanks for a very interesting keynote lecture
The high stability of amorphous salts is very intriguing, as one could think that ionic interactions would lead to a high lattice energy and favor crystallization. Do you observe a relationship between size or conformational flexibility or size difference between the drug molecule and coformer (i.e. salts that would have problems packing efficiently into a crystal lattice) and amorphous stability?
Thomas Rades
This is a very good question. Actually, we have published a few articles on selection of co-formers. These may give some answers directly to your question, but there is still certainly a need to look into this further, as for example salt formation, leading to "stable" co-amorphous systems, appears to be easier with acidic drugs and basic amino acids and than the other way round.

Kasten G, Grohganz H, Rades T, Löbmann K, Development of a screening method for co-amorphous formulations of drugs and amino acids. European Journal of Pharmaceutical Sciences 95: 28 - 35 (2016)
Kasten G, Löbmann K, Grohganz H, Rades T, Co-former selection for co-amorphous drug-amino acid formulations. International Journal of Pharmaceutics 557: 366 - 373 (2019)
Chambers LI, Palmelund H, Löbmann K, Rades T, Musa OM, W. Steed JW, Predictive Identification of Co-formers in Co-amorphous Systems. European Journal of Pharmaceutical Sciences IN PRESS (2020) https://doi.org/10.1016/j.ejps.2020.105636



 
 
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