Solubility enhancement of rosuvastatin using co-crystal approach

Rosuvastatin has been used to treat hyperlipidemia commercially by reducing triglycerides, apolipoproteins, and low-density lipoproteins, increasing high-density lipoproteins, and decreasing triglycerides.

However, it is a BCS class II drug and has the problems of low aqueous solubility and low bioavailability. The cocrystal approach has been repeatedly used to improve the solubility of poorly soluble drugs, with potential to enhance other physicochemical properties. The cocrystal approach also shows a high degree of dependence on the manufacturing methods used to produce the same.

In this study, cocrystals of Rosuvastatin calcium have been synthesized using the amino acid coformers L-Glutamine and L-Asparagine. These cocrystals have been produced using two separate manufacturing techniques: spray drying and solvent evaporation.

Solubility studies were used to identify the manufacturing technique with better solubility parameters. The spray-drying approach showed a clear improvement in solubility compared to the solvent evaporation method, with cocrystals of Rosuvastatin:L-Asparagine showing a 4.95-fold increase in solubility, the highest observed. Solid-state characterization, such as Fourier-Transform Infrared spectroscopy, Differential Scanning calorimetry, and Powder X-Ray Diffraction, was performed on the shortlisted cocrystals, and dissolution studies were conducted to quantify the solubility enhancement observed upon cocrystallisation.

This study demonstrated that different manufacturing techniques significantly affect the solubility of rosuvastatin cocrystals. Cocrystals synthesized using two distinct coformers and methods showed notable differences, with spray drying producing superior cocrystals. These spray-dried cocrystals offer advantages for scaling up into continuous manufacturing suitable for industrial production.