title: Effect of high shear rate on stability of proteins: kinetic study.
abstract: Size-exclusion chromatography (SEC) was used to monitor the time-course of protein degradation induced by high shear rates during the formulation and manufacture of controlled-release pharmaceutical dosage forms. SEC with multi-angle laser light-scattering (MALLS) detection was used to characterize the aggregation products, determining their absolute molecular weight. A stability-indicating method was developed and validated to obtain reliable drug degradation data. The results obtained according to the ICH guidelines confirm that the system and methods proposed are suitable for their intended use. The degradation kinetics are influenced by the type of protein and the effect of the shear rate on their stability. Reversible pseudo-first order degradation kinetics were observed for bovine beta-lactoglobulin, whereas for human (HSA) and bovine serum albumin (BSA), a monomer-dimer transition was observed, independently of the rate of shear. However, trimer formation was also observed for HSA, especially at high shear rates. The kinetic model may thus be described as a two-step process: a monomer-dimer, and dimer-trimer transition.
authors.affiliation: Dpto. Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain. amoliva@ull.es
authors.forename: Alexis
authors.initials: A
authors.lastname: Oliva
authors.forename: Ana
authors.initials: A
authors.lastname: Santoveña
authors.forename: José
authors.initials: J
authors.lastname: Fariña
authors.forename: Matías
authors.initials: M
authors.lastname: Llabrés
mesh_terms: D000465:Algorithms; D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007700:Kinetics; D007782:Lactoglobulins / Q000737:chemistry; D008027:Light; D008970:Molecular Weight; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012709:Serum Albumin / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014783:Viscosity
chemical_list: D007782:Lactoglobulins; D011506:Proteins; D012709:Serum Albumin; D012710:Serum Albumin, Bovine