Coamorphous Active Pharmaceutical Ingredient–Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability

In the recent years, coamorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule coformer have appeared as alternatives to the use of either amorphous solid dispersions containing polymer or cocrystals of API and small molecule coformers, to improve the dissolution...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2018-01, Vol.107 (1), p.5-17
Main Authors: Newman, Ann, Reutzel-Edens, Susan M., Zografi, George
Format: Article
Language:English
Subjects:
Administration, Oral
amorphous
bioavailability
Biological Availability
Chemistry, Pharmaceutical - methods
cocrystals
Crystallization - methods
Pharmaceutical Preparations - chemistry
physical stability
Polymers - chemistry
Small Molecule Libraries - chemistry
solid dispersion
solubility
Solubility - drug effects
stabilization
Transition Temperature
Water - chemistry
Wettability - drug effects
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Summary:In the recent years, coamorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule coformer have appeared as alternatives to the use of either amorphous solid dispersions containing polymer or cocrystals of API and small molecule coformers, to improve the dissolution and oral bioavailability of poorly soluble crystalline API. This Commentary article considers the relative properties of amorphous solid dispersions and coamorphous systems in terms of methods of preparation; miscibility; glass transition temperature; physical stability; hygroscopicity; and aqueous dissolution. It also considers important questions concerning the fundamental criteria to be used for the proper selection of a small molecule coformer regarding its ability to form either coamorphous or cocrystal systems. Finally, we consider various aspects of product development that are specifically associated with the formulation of commercial coamorphous systems as solid oral dosage forms. These include coformer selection; screening; methods of preparation; preformulation; physical stability; bioavailability; and final formulation. Through such an analysis of coamorphous API-small molecule coformer systems, against the more widely studied API-polymer dispersions and cocrystals, it is believed that the strengths and weaknesses of coamorphous systems can be better understood, leading to more efficient formulation and manufacture of such systems for enhancing oral bioavailability.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2017.09.024