Abstract
The amorphous solid state offers an improved apparent solubility and dissolution rate. However, due to thermodynamic instability and recrystallization tendencies during processing, storage and dissolution, their potential application is limited. For this reason, the production of amorphous drugs with adequate stability remains a major challenge and formulation strategies based on solid molecular dispersions are being exploited. Co-amorphous systems are a new formulation approach where the amorphous drug is stabilized through strong intermolecular interactions by a low molecular co-former. This review covers several topics applicable to co-amorphous drug delivery systems. In particular, it describes recent advances in the co-amorphous composition, preparation and solid-state characterization, as well as improvements of dissolution performance and absorption are detailed. Examples of drug-drug, drug-carboxylic acid and drug-amino acid co-amorphous dispersions interacting via hydrogen bonding, π−π interactions and ionic forces, are presented together with corresponding final dosage forms.
Highlights
About 40% of the marketed and 90% of the drugs under development present low water solubility, resulting in poor and variable oral absorption, low bioavailability and unsatisfactory therapeutic efficacy [1,2]
The amorphous solid state offers improved apparent solubility and dissolution rate due to the lower energy barrier required to dissolve the molecules, and transformation of crystalline drug into amorphous is widely employed for increasing solubility
Tests with the indomethacin/naproxen 1:1 co-amorphous Solid dispersion (SD) demonstrated similar dissolution profiles for the two drugs with simultaneous release and increased stability compared to the crystalline or amorphous IND, which was attributed to formation of heterodimers [19]
Summary
About 40% of the marketed and 90% of the drugs under development present low water solubility, resulting in poor and variable oral absorption, low bioavailability and unsatisfactory therapeutic efficacy [1,2]. For stability reasons, the low solubility crystalline form of a drug is used in formulations. Different approaches have been explored such as salt formation, solid dispersions and amorphous homologues among others [3,4]. The amorphous solid state offers improved apparent solubility and dissolution rate due to the lower energy barrier required to dissolve the molecules, and transformation of crystalline drug into amorphous is widely employed for increasing solubility. New formulation strategies based on solid molecular dispersions are being exploited and co-amorphous dispersions is one of them with very promising results [6]
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