2 research outputs found
Influence of Secondary Interactions on the Structure, Sublimation Thermodynamics, and Solubility of Salicylate:4-Hydroxybenzamide Cocrystals. Combined Experimental and Theoretical Study
Cocrystal
screening of 4-hydroxybenzamide with a number of
salicylates (salicylic acid, SA; 4-aminosalicylic acid, PASA;
acetylsalicylic acid, ASA; and salicylsalicylic acid,
SSA) was conducted to confirm the formation of two cocrystals, [SA+4-OHBZA]
(1:1) and [PASA+4-OHBZA] (1:1). Their structures were determined using
single-crystal X-ray diffraction, and the hydrogen-bond network topology
was studied. Thermodynamic characteristics of salicylic acid cocrystal
sublimation were obtained experimentally. It was proved that PASA
cocrystallization with 4-OHBZA makes the drug more stable and prevents
the irreversible process of decarboxylation of PASA resulting in formation
of toxic 3-aminophenol. The pattern of non-covalent interactions
in the cocrystals is described quantitatively using solid-state density
functional theory followed by Bader analysis of the periodic electron
density. It has been found that the total energy of secondary interactions
between synthon atoms and the side hydroxyl group of the acid molecule
in [SA+4-OHBZA] (1:1) and [PASA+4-OHBZA] (1:1) cocrystals is comparable
to the energy of the primary acid–amide heterosynthon.
The theoretical value of the sublimation enthalpy of [SA+4-OHBZA],
231 kJ/mol, agrees fairly well with the experimental one, 272 kJ/mol.
The dissolution experiments with [SA+4-OHBZA] have proved that the
relatively large cocrystal stability in relation to the stability
of its components has a negative effect on the dissolution rate and
equilibrium solubility. The [PASA+4-OHBZA] (1:1) cocrystal showed
an enhancement of apparent solubility compared to that of the corresponding
pure active pharmaceutical ingredient, while their intrinsic dissolution
rates are comparable
Salicylamide Cocrystals: Screening, Crystal Structure, Sublimation Thermodynamics, Dissolution, and Solid-State DFT Calculations
A new
cocrystal of 2-hydroxybenzamide (A) with 4-acetamidobenzoic
acid (B) has been obtained by the DSC screening method. Thermophysical
analysis of the aggregate [A:B] has been conducted and a fusion diagram
has been plotted. Cocrystal formation from melts was studied by using
thermomicroscopy. A cocrystal single-crystal was grown and its crystal
structure was determined. The pattern of noncovalent interactions
has been quantified using the solid-state DFT computations coupled
with the Bader analysis of the periodic electron density. The sublimation
processes of A-B cocrystal have been studied and its thermodynamic
functions have been calculated. The classical method of substance
transfer by inert gas-carrier was chosen to investigate sublimation
processes experimentally. The lattice energy is found to be 143 ±
4 kJ/mol. It is lower than the sum of the corresponding values of
the cocrystal pure components. The theoretical value of the lattice
energy, 156 kJ/mol, is in reasonable agreement with the experimental
one. A ternary phase diagram of solubility (A-B–ethanol) has
been plotted and the areas with solutions for growing thermodynamically
stable cocrystals have been determined