Cocrystal formation of loratadine-succinic acid and its improved solubility.

OBJECTIVES

Loratadine belongs to Class II compound of biopharmaceutics classification system (BCS) due its low solubility and high membrane permeability. Cocrystal is a system of multicomponent crystalline that mostly employed to improve solubility. Succinic acid is one of common coformer in cocrystal modification. This research aims to investigate cocrystal formation between loratadine and succinic acid and its effect on solubility property of loratadine.

METHODS

Cocrystal of loratadine-succinic acid was prepared by solution method using methanol as the solvent. Cocrystal formation was identified under observation of polarization microscope and analysis of the binary phase diagram. The cocrystal phase was characterized by differential thermal analysis (DTA), powder X-ray diffraction (PXRD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). Solubility study was conducted in phosphate-citrate buffer pH 7.0 ± 0.5 at 30 ± 0.5 °C.

RESULTS

Loratadine is known to form cocrystal with succinic acid in 1:1 M ratio. Cocrystal phase has lower melting point at 110.9 °C. Powder diffractograms exhibited new diffraction peaks at 2 of 5.28, 10.09, 12.06, 15.74, 21.89, and 28.59° for cocrystal phase. IR spectra showed that there was a shift in C=O and O-H vibration, indicating intermolecular hydrogen bond between loratadine and succinic acid. SEM microphotographs showed different morphology for cocrystal phase. Loratadine solubility in cocrystal phase was increased up to 2-fold compared to loratadine alone.

CONCLUSIONS

Cocrystal of loratadine and succinic acid is formed by stoichiometry of 1:1 via C=O and H-O interaction. Cocrystal phase shows different physicochemical properties and responding to those properties, it shows improved loratadine solubility as well.