Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement

Abstract

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO₂) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus^® (SOL) at temperatures below polymer's glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug-polymer ratio on the successful preparation of SDs. The SIM-SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO₂ processing conditions and drug-polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM-SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM-SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Keywords: drug dissolution; simvastatin; soluplus; supercritical carbon dioxide.

Figure 1

The structure of Simvastatin (A) and Soluplus (B).

Figure 2

DSC thermogram of Soluplus^®, Simvastatin, physical mixture (PM10, PM20, and PM30 and solid dispersions (SD10, SD20, and SD30) prepared at 50 °C and 150 bar.

Figure 3

XRD diffractogram of Soluplus^®, Simvastatin, physical mixture (PM10, PM20, and PM30 and solid dispersions (SD10, SD20, and SD30) prepared at 50 °C and 150 bar.

Figure 4

ATR-FTIR spectra of Soluplus^®, Simvastatin, physical mixture (PM10, PM20, and PM30 and solid dispersions (SD10, SD20, and SD30) prepared at 50 °C and 150 bar.

Figure 5

SEM micrographs (200×) of (a) Soluplus^®, (b) Simvastatin (inset-2000×), and solid dispersions ((c) SD10 and (d) SD30).

Figure 6

Dissolution profiles of bulk SIM, PMs, and SDs at 37 °C in pH 7 phosphate buffer containing 0.2% w/v SDS (n = 3).

Figure 7

Drug dissolution of pure SIM, scCO₂ processed SIM, SD, and PM after 2, 10, 20, and 45 min.