Rosuvastatin cocrystals: an attempt to modulate physicochemical parameters

Abstract

Background The meager physicochemical properties like low solubility and low dissolution rate of rosuvastatin calcium remain as an obstruction for formulation development. In the present work, we explore the evolution of rosuvastatin cocrystal, which may offer the synergetic physico-chemical properties of the drug. Cocrystal crafting depends on two possible intermolecular interactions; heteromeric and the homomeric selection of compounds with complementary functional groups are contemplated as a possible cause of supramolecular synthons in cocrystal formation. Specifically, cocrystals of rosuvastatin with l-asparagine and l-glutamine with molar ratio (1:1) were fabricated by using slow solvent evaporation and slow evaporation techniques. Novel cocrystals of rosuvastatin-asparagine (RSC-C) and rosuvastatin-glutamine (RSC-G) cocrystals obtained by slow solvent evaporation were utilized for preliminary investigation and further scale-up was done by using the solvent evaporation technique. Results The novel cocrystals showed a new characteristic of powder X-ray diffraction, thermograms of differential scanning calorimetry, 1H liquid FT-NMR spectra, and scanning electron microscopy. These results signify the establishment of intermolecular interaction within the cocrystals. In both the novel cocrystals, rosuvastatin was determined to be engaged in the hydrogen bond interaction with the complementary functional groups of l-asparagine and l-glutamine. Compared with the pure rosuvastatin, RSC-C and RSC-G cocrystal showed 2.17-fold and 1.60-fold improved solubility respectively. The dissolution test showed that the RSC-C and RSC-G cocrystal exhibited 1.97-fold and 1.94-fold higher dissolution rate than the pure rosuvastatin in pH6.8 phosphate buffer respectively. Conclusion Modulation in the chemical environment, improvement in the solubility, and dissolution rate demonstrated the benefit of co-crystallization to improve the physicochemical properties of the drug. Graphical abstract

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

“…Recently, Vemuri and Lankalapalli improved RST solubility using amino acids through hydrogen-bonding interaction for co-crystal formation. 35 Additionally, RST possessed the carboxylic functional group which may impart surface propensity (surface behavior) of the aqueous solution and binary system for the air/water interface by reducing surface tension to some extend at explored temperature. 36 There are several factors responsible to influence surface (surface propensities) behavior of molecules bearing carboxylic groups such as (a) molecular size, (b) saturation and unsaturation in the compound, (c) hydrophobicity/hydrophilicity, (d) molecular density, (e) number of carboxylic groups in the molecules, (f) strength of interaction (weak surface propensity due to strong interaction via three hydrogen bonds in citric acid compared to oxalic acid), and (g) orientation of molecules at the surface/interface.…”

“…The increased solubility of RST by PEG400 might be attributed to hydrogen-bond formation preferentially over solute–solvent polar interactions, decreased surface tension, improved wettability by PEG400, and other factors. Recently, Vemuri and Lankalapalli improved RST solubility using amino acids through hydrogen-bonding interaction for co-crystal formation . Additionally, RST possessed the carboxylic functional group which may impart surface propensity (surface behavior) of the aqueous solution and binary system for the air/water interface by reducing surface tension to some extend at explored temperature .…”