Crystal Structural Analysis of DL-Mandelate Salt of Carvedilol and Its Correlation with Physicochemical Properties

Abstract

A 1:1 salt of carvedilol (CVD), an anti-hypertensive drug, with DL-mandelic acid (DL-MA) was crystallized from ethanol and the structure was characterized by X-ray single-crystal diffraction, revealing salt formation by transfer of an acidic proton from the COOH group of MA to the aliphatic (acyclic) secondary amino NH group of CVD. The crystal structure is triclinic, with a P-1 space group and unit cell parameters a = 9.8416(5) Å, b = 11.4689(5) Å, c = 14.0746(7) Å, α = 108.595(8), β = 95.182(7), γ = 107.323(8), V = 1406.95(15) Å3, and Z = 2. The asymmetric unit contained one protonated CVD and one MA anion, linked via an N+–H∙∙∙O¯ strong hydrogen bond and a ratio of 1:1. As previously reported, the thermal, spectroscopic, and powder X-ray diffraction properties of the salt of CVD with DL-MA (CVD_DL-MA) differed from CVD alone. The intrinsic dissolution rate of CVD_DL-MA was about 10.7 times faster than CVD alone in a pH 6.8 buffer.

Crystal Structures of Antiarrhythmic Drug Disopyramide and Its Salt with Phthalic Acid

“…DPA and PA were purchased from Tokyo Chemical Industry Co. Ltd. (T All other analytical-grade solvents and reagents were commercially obtain without further purification. We are going to focus on the crystallization and crystal engineering research on active pharmaceutical ingredients (APIs), particularly on improving the physicochemical properties of drug molecules by undertaking polymorphic study [45], making multicomponent crystals [46], such as its solvates [47], cocrystals [48], and salts [49]. In this report, we discuss the X-ray single-crystal structure of the lower melting temperature form of DPA and novel DPA_PA salt [Phthalic acid (PA), Figure 1b], detailed crystal structure analysis and its characterization.…”

“…We are going to focus on the crystallization and crystal engineering re tive pharmaceutical ingredients (APIs), particularly on improving the phy properties of drug molecules by undertaking polymorphic study [45], makin ponent crystals [46], such as its solvates [47], cocrystals [48], and salts [49]. I we discuss the X-ray single-crystal structure of the lower melting tempera DPA and novel DPA_PA salt [Phthalic acid (PA), Figure 1b], detailed crys analysis and its characterization.…”

Structure determination of organic compounds by a fit to the pair distribution function from scratch without prior indexing

“…Structure determination is an important step in the investigation of molecular solids due to the correlation of the molecular arrangement within the crystal and solid-state properties, such as physico-chemical stability, solubility, bioavailability, and optical and magnetic properties. Knowledge of the crystal structure is crucial to explain or predict these physical and chemical properties (Hata et al, 2020), as well as to optimize them in terms of crystal engineering (Desiraju, 2003;Schmidt et al, 2007). The average crystal structure can be determined by single-crystal analysis or structure determination from powder diffraction data (SDPD) (David et al, 2002).…”