title: Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer.
abstract: We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano-milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP-100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine.
authors.forename: K
authors.initials: K
authors.lastname: Yuminoki
authors.forename: S
authors.initials: S
authors.lastname: Tachibana
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Takatsuka
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000295:instrumentation*; D005079:Excipients; D008297:Male; D053758:Nanoparticles; D036103:Nanotechnology / Q000295:instrumentation*; D010316:Particle Size; D010672:Phenytoin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000927:Anticonvulsants; D005079:Excipients; D010672:Phenytoin