title: Cryoprotectants for freeze drying of drug nano-suspensions: effect of freezing rate.
abstract: Drug nanoparticles are often prepared in a liquid medium, and a drying method such as freeze drying is used to convert them to an oral solid dosage form. When the dried form is reconstituted in an aqueous system, it may be redispersed to achieve its original particle size. The redispersibility of dried nanoparticles depends on the parameters of the freeze drying process. In this study, an apparatus with a freezing rate gradient was used to systematically investigate the effect of cryoprotectants on the redispersibility of nanoparticles as a function of freezing rate. Sucrose, lactose, mannitol, and polyethylene glycol were used as cryoprotectants for a naproxen nano-suspension. A fast freezing rate and a high cryoprotectant concentration were generally favored. However, under certain conditions, a slower freezing rate resulted in better redispersibility. This is probably because slow freezing can produce a more cryo-concentrated liquid phase, and the concentrated cryoprotectant in the liquid phase can more effectively protect the nanoparticles. An irreversible aggregation map was constructed as a function of the freezing rate and the cryoprotectant concentration, and shows both the favorable and unfavorable effects of cryoprotectants.
authors.affiliation: Department of Chemical Engineering and Materials Science, Chung-Ang University, 221, Heukseok-dong, Dongjak-gu, Seoul 156-756, South Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Sujung
authors.initials: S
authors.lastname: Kim
authors.forename: Jonghwi
authors.initials: J
authors.lastname: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D003451:Cryoprotective Agents / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods*; D005615:Freezing; D007700:Kinetics; D007785:Lactose; D008353:Mannitol; D053758:Nanoparticles; D009288:Naproxen / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols; D013395:Sucrose; D013535:Suspensions; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003451:Cryoprotective Agents; D005079:Excipients; D013535:Suspensions; D008353:Mannitol; D011092:Polyethylene Glycols; D013395:Sucrose; D009288:Naproxen; D007785:Lactose