Processing and formulation of drug nanoparticles by ternary cogrinding with methacrylic copolymer and sucrose fatty acid esters

Drug nanoparticles were prepared by cogrinding three components: a drug, a methacrylic copolymer, and sucrose fatty acid ester (SE). A high nanoparticle yield was obtained when cholesterol-lowering probucol (PBC), a poorly water–soluble drug, was used in the cogrinding process with D-1811, an SE with stearic acid as the fatty acid and the hydrophile–lipophile balance (HLB): 11. Investigation of the influence of HLB on SEs constituted with stearates revealed that the nanoparticle yield increased with increasing HLB of the SE; a particle-size distribution of about 100 nm (thought to originate from the drug) was observed. The PBC crystallinity was analyzed by powder X-ray diffraction and Raman spectroscopy before and after grinding. Its crystalline form changed from form I to form II with partial generation of the amorphous state. Granules with improved drug solubility and controlled-release performance were prepared by coating the particles with an aqueous suspension of the coground product. Observation of the coated granule surfaces by SEM and polarization microscopy revealed about a 10-μm-thick coating layer. In a dissolution test, controlled drug-release characteristics were observed under intestinal solubility conditions. Based on these results, functional pharmaceutical granules with enteric and sustained drug release were prepared.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Drug nanoparticles were prepared by ternary cogrinding system. ► Probucol was coground with a methacrylic copolymer and sucrose fatty acid ester. ► The sucrose–stearic acid ester enabled a high yield of drug nanoparticles. ► Pharmaceutical granules containing drug nanoparticles was successfully prepared.