Multi-component supramolecular gels for the controlled crystallization of drugs: Synergistic and antagonistic effects

TY - JOUR

T1 - Multi-component supramolecular gels for the controlled crystallization of drugs

T2 - Synergistic and antagonistic effects

AU - Buendía, Julia

AU - Matesanz, Emilio

AU - Smith, David K.

AU - Sánchez, Luis

N1 - © Royal Society of Chemistry 2015. This is an author produced version of a paper published in CyrstEngComm. Uploaded in accordance with the publisher's self-archiving policy.

PY - 2015/9/14

Y1 - 2015/9/14

N2 - The applicability of multi-component gels, based on the combination of Lys-based dendrons and alkyl amines, for the crystallization of common drugs is presented. The results presented herein demonstrate that active pharmaceutical ingredients (APIs) with no carboxylic acid in their structure readily crystallize inside the organogels formed by a second generation lysine-based dendron (G2-Lys) and aliphatic amines. The thermodynamic parameters (ΔHdiss, ΔSdiss and ΔGdiss) of the corresponding three-component mixture (API + G2-Lys dendron + amine) have been calculated by using VT 1H NMR. Interestingly, the presence of carbamazepine (CBZ) in the mixture of G2-Lys and decylamine allows efficient gelation at room temperature in contrast with the behaviour observed for an unmodified G2-Lys dendron and decylamine mixture that only forms toluene gels at -20 °C-a synergistic effect in which the API enhances gelation. On the other hand, aspirin (ASP) or indomethacine (IND), that possess a carboxylic acid in their structure, do not crystallize inside the organogel formed by G2-Lys dendron and the amine-indeed they prevent formation of the gel. The Ka values of the complexes G2-Lys⋯decylamine and IND⋯decylamine have been calculated by 1H NMR titrations in toluene-d8. The higher Ka value for the complex IND⋯decylamine justifies that this pair is thermodynamically favoured thus preventing the formation of the complex between the Lys-based dendron and the amine, which underpins gel fibre assembly, and also preventing effective crystallization of the API-an antagonistic effect. Overall, these results demonstrate the active roles played by all components when multi-component gels are used for API crystallisation.

AB - The applicability of multi-component gels, based on the combination of Lys-based dendrons and alkyl amines, for the crystallization of common drugs is presented. The results presented herein demonstrate that active pharmaceutical ingredients (APIs) with no carboxylic acid in their structure readily crystallize inside the organogels formed by a second generation lysine-based dendron (G2-Lys) and aliphatic amines. The thermodynamic parameters (ΔHdiss, ΔSdiss and ΔGdiss) of the corresponding three-component mixture (API + G2-Lys dendron + amine) have been calculated by using VT 1H NMR. Interestingly, the presence of carbamazepine (CBZ) in the mixture of G2-Lys and decylamine allows efficient gelation at room temperature in contrast with the behaviour observed for an unmodified G2-Lys dendron and decylamine mixture that only forms toluene gels at -20 °C-a synergistic effect in which the API enhances gelation. On the other hand, aspirin (ASP) or indomethacine (IND), that possess a carboxylic acid in their structure, do not crystallize inside the organogel formed by G2-Lys dendron and the amine-indeed they prevent formation of the gel. The Ka values of the complexes G2-Lys⋯decylamine and IND⋯decylamine have been calculated by 1H NMR titrations in toluene-d8. The higher Ka value for the complex IND⋯decylamine justifies that this pair is thermodynamically favoured thus preventing the formation of the complex between the Lys-based dendron and the amine, which underpins gel fibre assembly, and also preventing effective crystallization of the API-an antagonistic effect. Overall, these results demonstrate the active roles played by all components when multi-component gels are used for API crystallisation.

UR - http://www.scopus.com/inward/record.url?scp=84945306169&partnerID=8YFLogxK

U2 - 10.1039/c5ce01293g

DO - 10.1039/c5ce01293g

M3 - Article

AN - SCOPUS:84945306169

SN - 1466-8033

VL - 17

SP - 8146

EP - 8152

JO - CrystEngComm

JF - CrystEngComm

IS - 42

ER -