title: Product mass transfer resistance directly determined during freeze-drying cycle runs using tunable diode laser absorption spectroscopy (TDLAS) and pore diffusion model.
abstract: The pore diffusion model is used to express the dry layer mass transfer resistance, [Formula: see text], as a function of the ratio r(e)/?, where r(e) is the effective pore radius and ? is the tortuosity factor of the dry layer. Using this model, the effective pore radius of the dry layer can be estimated from the sublimation rate and product temperature profiles measured during primary drying. Freeze-drying cycle runs were performed using the LyoStar II dryer (FTS Systems), with real-time sublimation rate profiles during freeze drying continuously measured by tunable diode laser absorption spectroscopy (TDLAS). The formulations chosen for demonstration of the proposed approach include 5% mannitol, 5% sucrose, 5% lactose, 3% mannitol plus 2% sucrose, and a parenteral nutrition formulation denoted VitaM12. The three different methods used for determination of the product resistance are: (1) Using both the sublimation rate and product temperature profiles, (2) using the sublimation rate profile alone, and (3) using the product temperate profile alone. Unlike the second and third methods, the computation procedure of first method does not need solution of the complex heat and mass transfer equations.
authors.affiliation: BioPharma Solutions, Baxter Healthcare Corporation, Bloomington, Indiana, IN 47403, USA. wei_kuu@baxter.com
authors.forename: Wei Y
authors.initials: WY
authors.lastname: Kuu
authors.forename: Kevin R
authors.initials: KR
authors.lastname: O'Bryan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hardwick
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Paul
mesh_terms: D000465:Algorithms; D004058:Diffusion; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying / Q000379:methods*; D007785:Lactose / Q000737:chemistry; D054023:Lasers, Semiconductor; D008353:Mannitol / Q000737:chemistry; D008956:Models, Chemical; D013057:Spectrum Analysis; D000074706:Sublimation, Chemical; D013395:Sucrose / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D014815:Vitamins / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D014815:Vitamins; D014867:Water; D008353:Mannitol; D013395:Sucrose; D007785:Lactose