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Stabilization of quinapril by incorporating hydrogen bonding interactions.

Roy BN, Singh GP, Godbole HM, Nehate SP - Indian J Pharm Sci (2009)

Bottom Line: In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate.Nitromethane solvate was found to be more stable compared to other known solvates.Quinapril tris(hydroxymethyl)amino methane salt found to be stable even at 80 degrees for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity.

View Article: PubMed Central - PubMed

Affiliation: Lupin Ltd. (Research Park), 46A, 47A - Nande Village, Mulshi Taluka, Pune-411 042, India.

ABSTRACT
In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate. Nitromethane solvate was found to be more stable compared to other known solvates. Single crystal X-ray diffraction analysis of quinapril nitromethane solvate shows intermolecular hydrogen bonding between quinapril molecule and nitromethane. Stabilization of quinapril by forming strong hydrogen bonding network as in case of co-crystals was further studied by forming co-crystal with tris(hydroxymethyl)amino methane. Quinapril free base forms a stable salt with tris(hydroxymethyl)amino methane not reported earlier. Quinapril tris(hydroxymethyl)amino methane salt found to be stable even at 80 degrees for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity. As expected single crystal X-ray diffraction analysis reveals tris(hydroxymethyl)amino methane salt of quinapril shows complex hydrogen bonding network between the two entities along with ionic bond. The properties of this stable salt - stable in solid as well as solution phase, might lead to an alternate highly stable formulation.

No MeSH data available.


Steps in the degradation of quinapril hydrochloride.Schematic representation showing various steps involved during degradation of quinapril hydrochloride. - HCl: escape of hydrogenchloride, - H2O: escape of water molecule
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Figure 0002: Steps in the degradation of quinapril hydrochloride.Schematic representation showing various steps involved during degradation of quinapril hydrochloride. - HCl: escape of hydrogenchloride, - H2O: escape of water molecule

Mentions: Desolvation of stoicheometric solvates most of the times lead to a different crystal structure or results in a disordered or amorphous state[9], with some exceptions[10–13]. In case of quinapril hydrochloride solvates, the product gets totally converted to an amorphous solid on desolvation. On heating, solid quinapril hydrochloride gets converted to the diketopiperazine impurity, in the solid stage escape of hydrogen chloride is the rate limiting step, and in case of solution phase, formation of quinapril zwitterions is the rate limiting step, which can be accelerated by increasing the pH of the solution[14]. The schematic representation of various steps involved in formation of diketopiperazine impurity as described by Li et al[14] is provided in fig. 2.


Stabilization of quinapril by incorporating hydrogen bonding interactions.

Roy BN, Singh GP, Godbole HM, Nehate SP - Indian J Pharm Sci (2009)

Steps in the degradation of quinapril hydrochloride.Schematic representation showing various steps involved during degradation of quinapril hydrochloride. - HCl: escape of hydrogenchloride, - H2O: escape of water molecule
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2865811&req=5

Figure 0002: Steps in the degradation of quinapril hydrochloride.Schematic representation showing various steps involved during degradation of quinapril hydrochloride. - HCl: escape of hydrogenchloride, - H2O: escape of water molecule
Mentions: Desolvation of stoicheometric solvates most of the times lead to a different crystal structure or results in a disordered or amorphous state[9], with some exceptions[10–13]. In case of quinapril hydrochloride solvates, the product gets totally converted to an amorphous solid on desolvation. On heating, solid quinapril hydrochloride gets converted to the diketopiperazine impurity, in the solid stage escape of hydrogen chloride is the rate limiting step, and in case of solution phase, formation of quinapril zwitterions is the rate limiting step, which can be accelerated by increasing the pH of the solution[14]. The schematic representation of various steps involved in formation of diketopiperazine impurity as described by Li et al[14] is provided in fig. 2.

Bottom Line: In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate.Nitromethane solvate was found to be more stable compared to other known solvates.Quinapril tris(hydroxymethyl)amino methane salt found to be stable even at 80 degrees for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity.

View Article: PubMed Central - PubMed

Affiliation: Lupin Ltd. (Research Park), 46A, 47A - Nande Village, Mulshi Taluka, Pune-411 042, India.

ABSTRACT
In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate. Nitromethane solvate was found to be more stable compared to other known solvates. Single crystal X-ray diffraction analysis of quinapril nitromethane solvate shows intermolecular hydrogen bonding between quinapril molecule and nitromethane. Stabilization of quinapril by forming strong hydrogen bonding network as in case of co-crystals was further studied by forming co-crystal with tris(hydroxymethyl)amino methane. Quinapril free base forms a stable salt with tris(hydroxymethyl)amino methane not reported earlier. Quinapril tris(hydroxymethyl)amino methane salt found to be stable even at 80 degrees for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity. As expected single crystal X-ray diffraction analysis reveals tris(hydroxymethyl)amino methane salt of quinapril shows complex hydrogen bonding network between the two entities along with ionic bond. The properties of this stable salt - stable in solid as well as solution phase, might lead to an alternate highly stable formulation.

No MeSH data available.