Co-crystallization Attempts of Paracetamol and Amikacin with Organic Boronic Acids
DOI:
https://doi.org/10.60988/p.v38i2.306Keywords:
Pharmaceutical co-crystals, Co-crystallization, Crystal engineering, Hydrogen bonding, Solubility enhancementAbstract
The problems associated with low aqueous solubility and bioavailability are still not overcome by various active pharmaceutical ingredients. Recently, crystal engineering and pharmaceutical cocrystalization have been shown to be beneficial in enhancing pharmaceutical properties of compounds, even if their molecular structures remain unchanged. The objective of the study was to examine the possibility of utilizing certain specific organic boronic acids as co-formers in cocrystalization of the two most common APIs, namely, paracetamol, and amikacin, in search of new compounds that may have more applications in pharmaceutical use. The crystallization process was carried out with a mixture of phenylboronic acids and substituted phenylboronic acids in varying stoichiometric proportions and paracetamol and amikacin APIs. Slow solution evaporation was used as the basic method of crystallization. The resulting crystals were characterized by single-crystal analysis and thermal analysis regarding formation verification of cocrystals. It was found that despite the presence of various potential acceptor and donor sites in APIs and their predicted compatibility displayed by their structures concerning boronic acids, no new cocrystals could be prepared under various conditions tested throughout the study. The effect has created a method for isolating crystals from original APIs used over time. The obtained results indicate that the formation of pharmaceutical co-crystals with organic boronic acids is API-dependent and is not necessarily successful when favorable intermolecular interaction is expected. There is value in reporting negative results to improve understanding regarding principles for co-crystal designs and future crystal engineering.
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