Racemic (5,6-bis 2-methyl propanoic acid-1,2,3,4-tetrahydro-naphtalen-2-yl)-methylammonium chloride, CHF-1035, under clinical investigation for the treatment of congestive heart failure, was here characterised by Raman and IR spectroscopies coupled with thermal analysis (thermogravimetry and differential scanning calorimetry). These techniques proved suitable for investigating the presence of different polymorphic forms, their relative stability and interconversion tendency in relation to industrial manufacturing processes undergone by the drug (i.e. grinding, compression, heating). Crystallisation experiments were carried out and two different CHF-1035 polymorphic forms were identified. Both grinding and heating revealed to cause a polymorphic transformation of the drug crystal form. It was hypothesised that a change in molecular packing occurs in the drug by effect of both treatments. The possible sources of polymorphism were identified in the -OCyOCH(CH3) groups and in the saturated ring. The non-ground sample showed two endothermic transitions; since they are reversible and not due to desolvation processes the system is probably enantiotropic.
Vibrational and thermal characterization of a new chiral drug under investigation for the therapy of congestive heart failure
Torreggiani A;
2002
Abstract
Racemic (5,6-bis 2-methyl propanoic acid-1,2,3,4-tetrahydro-naphtalen-2-yl)-methylammonium chloride, CHF-1035, under clinical investigation for the treatment of congestive heart failure, was here characterised by Raman and IR spectroscopies coupled with thermal analysis (thermogravimetry and differential scanning calorimetry). These techniques proved suitable for investigating the presence of different polymorphic forms, their relative stability and interconversion tendency in relation to industrial manufacturing processes undergone by the drug (i.e. grinding, compression, heating). Crystallisation experiments were carried out and two different CHF-1035 polymorphic forms were identified. Both grinding and heating revealed to cause a polymorphic transformation of the drug crystal form. It was hypothesised that a change in molecular packing occurs in the drug by effect of both treatments. The possible sources of polymorphism were identified in the -OCyOCH(CH3) groups and in the saturated ring. The non-ground sample showed two endothermic transitions; since they are reversible and not due to desolvation processes the system is probably enantiotropic.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
