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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.


Quinapril tris crystal structure: One-dimensional chain propagating along the [010] direction.
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Figure 0006: Quinapril tris crystal structure: One-dimensional chain propagating along the [010] direction.

Mentions: An ORTEP[37] view of asymmetric unit of quinapril tris salt with atom numbering scheme is shown in fig. 5. The conformation of the quinapril molecule is established by the torsion angles N1-C12-C13-N2 150.3(5)˚, N2-C16-C17-C18 -62.5(6)˚ and C16-C17-C18-C19 -167.8(5)˚. The hetero ring (C1/N1/C3/C4/C9/C10) assumes a screw-boat conformation with ring puckering parameters[41] Q=0.551(5) Å, θ=69.7(6)˚ and φ=-27.9(6)˚, respectively. The molecular structure of the title compound is stabilized by several intermolecular hydrogen bonds (Table 7) between quinapril and tris molecules. Intermolecular N(3)-H(31A)O(2), O(8)-H(8A)O(3) and O(7)-H(7A)O(6) hydrogen bonds connect the molecules into R33(18) rings which are corner fused to form one-dimensional polymeric chains propagating along the [010] direction (fig. 6). Adjacent one-dimensional chains are joined by O(6)-H(6A)O(2) and N(3)-H(31B) O(1) hydrogen bonds forming molecular channels which are further linked via C-H hydrogen bonds and interactions, so generating a three-dimensional framework (fig. 7).


Stabilization of quinapril by incorporating hydrogen bonding interactions.

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

Quinapril tris crystal structure: One-dimensional chain propagating along the [010] direction.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0006: Quinapril tris crystal structure: One-dimensional chain propagating along the [010] direction.
Mentions: An ORTEP[37] view of asymmetric unit of quinapril tris salt with atom numbering scheme is shown in fig. 5. The conformation of the quinapril molecule is established by the torsion angles N1-C12-C13-N2 150.3(5)˚, N2-C16-C17-C18 -62.5(6)˚ and C16-C17-C18-C19 -167.8(5)˚. The hetero ring (C1/N1/C3/C4/C9/C10) assumes a screw-boat conformation with ring puckering parameters[41] Q=0.551(5) Å, θ=69.7(6)˚ and φ=-27.9(6)˚, respectively. The molecular structure of the title compound is stabilized by several intermolecular hydrogen bonds (Table 7) between quinapril and tris molecules. Intermolecular N(3)-H(31A)O(2), O(8)-H(8A)O(3) and O(7)-H(7A)O(6) hydrogen bonds connect the molecules into R33(18) rings which are corner fused to form one-dimensional polymeric chains propagating along the [010] direction (fig. 6). Adjacent one-dimensional chains are joined by O(6)-H(6A)O(2) and N(3)-H(31B) O(1) hydrogen bonds forming molecular channels which are further linked via C-H hydrogen bonds and interactions, so generating a three-dimensional framework (fig. 7).

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.