TITLE: QUALITATIVE PHASE IDENTIFICATION & CRYSTAL STRUSTURE ANALYSIS OF ISONICOTINAMIDE POLYMORPHS.
INTRODUCTION
The science of crystallography is important in stability studies and determination of solid state molecule or particles. Isonicotinamide (pyridine -4- carboxamide) is the amide form of isonicotinic acid which exists as different polymorphs. Isonicotinamide finds extensive use in the pharmaceutical industry because of its good anti-tubercular, anti-bacterial, anti-pyretic and fibrinolytic properties (Li et al. 2016). The crystal structure and polymorphs of Active pharmaceutical ingredients (APIs) has been found important as one of the factors that decides the effectiveness of a drug. In recent times, the stability and aqueous solubility …show more content…
2011). A work by (Blagden et al. 2007) reported that the formation of different polymorphs /solvates of an API can be influenced by factors such as solvents /solvent composition, cooling profile, operating mode (cooling or anti-solvent crystallization), additives and concentration of solute used during the process. (Kulkarni et al. 2012) established the relationship between solvent and polymorph nucleation in Isonicotinamide. Three (3) forms of Isonicotinamide (I, II and IV) were crystalized using solvents such as nitrobenzene, acetone, nitromethane, methanol, ethanol, 2-propanol, dioxane and chloroform. It was found that the hydrogen bonding behaviour of Isonicotinamide is of interest since different polymorphs exhibited different hydrogen bonding and molecular …show more content…
1 PXRD Simulation pattern for isonicotinamide polymorph I.
Fig. 2 PXRD Simulation pattern for isonicotinamide polymorph I.
Ref. code EHOWIH02 is a polymorph form II obtained from crystallization using solvent ethanol or water or tetrahydrofuran or dioxane. This polymorph has 8 molecule of isonicotinamide in one asymetric unit (Z=8) and the molecules are arranged in a head to tail pattern with the pyridine group bonding to the amide group of the adjacent molecule vertically along c-axis as seen in fig. 3. This polymorphic form II of isonicotinamide is most stable form at room temperature because it posses a better hydrogen bonding better than other polymorphs (Kulkarni et al. 2012).
Fig. 3 crystal packing image for isonicotinamide polymorph II
For the purpose of this work, PXRD simulations of polymorph II and the test sample of Isonicotinamide shows some degree of similarity between the two molecules as shown in fig. 4. This similarity may be accounted for by the solvent used in the crystallization process of the molecules
Fig. 4 PXRD simulation pattern showing polymorph II and sample
INTRODUCTION
The science of crystallography is important in stability studies and determination of solid state molecule or particles. Isonicotinamide (pyridine -4- carboxamide) is the amide form of isonicotinic acid which exists as different polymorphs. Isonicotinamide finds extensive use in the pharmaceutical industry because of its good anti-tubercular, anti-bacterial, anti-pyretic and fibrinolytic properties (Li et al. 2016). The crystal structure and polymorphs of Active pharmaceutical ingredients (APIs) has been found important as one of the factors that decides the effectiveness of a drug. In recent times, the stability and aqueous solubility …show more content…
2011). A work by (Blagden et al. 2007) reported that the formation of different polymorphs /solvates of an API can be influenced by factors such as solvents /solvent composition, cooling profile, operating mode (cooling or anti-solvent crystallization), additives and concentration of solute used during the process. (Kulkarni et al. 2012) established the relationship between solvent and polymorph nucleation in Isonicotinamide. Three (3) forms of Isonicotinamide (I, II and IV) were crystalized using solvents such as nitrobenzene, acetone, nitromethane, methanol, ethanol, 2-propanol, dioxane and chloroform. It was found that the hydrogen bonding behaviour of Isonicotinamide is of interest since different polymorphs exhibited different hydrogen bonding and molecular …show more content…
1 PXRD Simulation pattern for isonicotinamide polymorph I.
Fig. 2 PXRD Simulation pattern for isonicotinamide polymorph I.
Ref. code EHOWIH02 is a polymorph form II obtained from crystallization using solvent ethanol or water or tetrahydrofuran or dioxane. This polymorph has 8 molecule of isonicotinamide in one asymetric unit (Z=8) and the molecules are arranged in a head to tail pattern with the pyridine group bonding to the amide group of the adjacent molecule vertically along c-axis as seen in fig. 3. This polymorphic form II of isonicotinamide is most stable form at room temperature because it posses a better hydrogen bonding better than other polymorphs (Kulkarni et al. 2012).
Fig. 3 crystal packing image for isonicotinamide polymorph II
For the purpose of this work, PXRD simulations of polymorph II and the test sample of Isonicotinamide shows some degree of similarity between the two molecules as shown in fig. 4. This similarity may be accounted for by the solvent used in the crystallization process of the molecules
Fig. 4 PXRD simulation pattern showing polymorph II and sample