TY - JOUR
T1 - Processing and formulation of drug nanoparticles by ternary cogrinding with methacrylic copolymer and sucrose fatty acid esters
AU - Hida, Yuuki
AU - Fukami, Toshiro
AU - Suzuki, Naoto
AU - Suzuki, Toyofumi
AU - Tomono, Kazuo
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Cogrinding
KW - Methacrylic copolymer
KW - Nanoparticle
KW - Probucol
KW - Sucrose fatty acid ester
UR - http://www.scopus.com/inward/record.url?scp=84870526122&partnerID=8YFLogxK
U2 - 10.1016/j.apt.2012.06.010
DO - 10.1016/j.apt.2012.06.010
M3 - Article
AN - SCOPUS:84870526122
SN - 0921-8831
VL - 24
SP - 246
EP - 251
JO - Advanced Powder Technology
JF - Advanced Powder Technology
IS - 1
ER -