Simvastatin nanosuspensions prepared using a combination of pH-sensitive and timed-release approaches for potential treatment of colorectal cancer

A dual pH- and time-dependent polymeric coated capsule was developed to achieve the site specificity of simvastatin (SIM) release in the colon. To improve the SIM solubility, soluplus-based nanosuspension of the drug were prepared by applying the anti-solvent crystallization technique; this was then followed by lyophilization. Particle size, polydispersity index, and saturation solubility were evaluated. The optimized nanosuspension was combined with SLS and freeze-dried before filling into hard gelatin capsules. Drug release characteristics of the coated capsules were studied in HCl 0.1 N, the phosphate buffers 6.8 and 7.4, and the simulated colonic fluid (pH 6.8). The in-vitro cytotoxic effects of SIM nanoparticles against HT29 cells were then evaluated using the MTT assay. The prepared nanoparticles were spherical with a mean size of 261.66 nm, the zeta potential of -18.20 and the dissolution efficiency of 59.71%. X-ray diffraction and differential scanning calorimetry studies showed that the nanosizing technique transformed the crystalline drug into the more soluble amorphous form. The coated capsules had no release in the gastric media, providing the specific delivery of SIM in the colon. The cytotoxic effect of the SIM nanoparticles was significantly increased, as compared to the free SIM. The findings, therefore, showed that the coated capsules using the two polymers of ethyl cellulose and Eudragit S100 could be suitable for the colon target delivery of SIM.

Automated summary

A dual pH- and time-dependent polymeric coated capsule was developed for site-specific release of simvastatin in the colon, using nanosuspension and anti-solvent crystallization technique to improve drug solubility. The nanosizing technique transformed the crystalline drug into a more soluble amorphous form, while the coated capsules provided specific delivery of simvastatin in the colon with enhanced cytotoxic effects of the drug nanoparticles against HT29 cells. The findings suggest that the coated capsules using ethyl cellulose and Eudragit S100 polymers could be suitable for colon-targeted delivery of simvastatin.