Container Surfaces Control Initiation of Cavitation and Resulting Particle Formation in Protein Formulations After Application of Mechanical Shock.


:Mechanical shock may cause cavitation in vials containing liquid formulations of therapeutic proteins and generate protein aggregates and other particulates. To test whether common formulation components such as protein molecules, air bubbles, or polysorbate 20 (PS20) micelles might nucleate cavitation, a high-speed video camera was used to detect cavitation in vials containing antibody formulations after application of controlled mechanical shock using a shock test. Higher concentrations of subvisible particles were found in formulations where cavitation had occurred. Bubbles trapped on vial surfaces were a primary site for cavitation nucleation; other potential cavitation nuclei were ineffective. The incidence of cavitation events observed after application of mechanical shock was lower in type I glass vials than in cyclic olefin polymer vials or in SiOPlas™ cyclic olefin polymer vials and correlated with the surface roughness of the different vials. To reduce the incidence of cavitation and the adsorption of mAb on glass-water and silicone oil-water interfaces and thus minimize protein damage due to cavitation, PS20, a common nonionic surfactant, was added to formulations. Addition of PS20 to formulations in glass and silicone oil-coated glass vials significantly reduced both incidence of mechanical shock-induced cavitation and the particle formation that resulted from cavitation events.


J Pharm Sci


Wu H,Chisholm CF,Puryear M,Movafaghi S,Smith SD,Pokhilchuk Y,Lengsfeld CS,Randolph TW




Has Abstract


2020-03-01 00:00:00














  • Correlation between chemical reactivity and the Hammett acidity function in amorphous solids using inversion of sucrose as a model reaction.

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    journal_title:Journal of pharmaceutical sciences

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    authors: Chatterjee K,Shalaev EY,Suryanarayanan R,Govindarajan R

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    journal_title:Journal of pharmaceutical sciences

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    authors: Caraballo I,Fernandez-Arevalo M,Holgado MA,Vela MT,Rabasco AM

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  • Determination of the influence of primary drying rates on the microscale structural attributes and physicochemical properties of protein containing lyophilized products.

    abstract::This work investigated the impact of primary drying conditions on the microstructure and protein stability of bovine serum albumin (BSA) containing lyophilized cakes. Two primary drying conditions were employed (termed 'conservative', slower drying rate and 'aggressive', higher drying rate) at two protein loadings (5 ...

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    journal_title:Journal of pharmaceutical sciences

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    journal_title:Journal of pharmaceutical sciences

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    authors: Zatz JL,Knapp S

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    authors: Alvarsson J,Arvidsson McShane S,Norinder U,Spjuth O

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    journal_title:Journal of pharmaceutical sciences

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    authors: Okudaira N

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    authors: Fink DW,Fink HC,Tolan JW,Blodinger J

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    authors: Ganjian F,Cutie AJ,Jochsberger T

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    authors: van Belle G,Leurgans S,Friel P,Guo SW,Yerby M

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  • Evaluation of in vivo bioequivalence methodology for topical clobetasol 17-propionate based on pharmacodynamic modeling using Chinese skin.

    abstract::The United States Food and Drug Administration recommends pilot dose duration-response and pivotal bioequivalence studies to be conducted using reflectance colorimetry for assessment of the in vivo bioequivalence of topical dermatologic corticosteroids. The major objectives of the present studies were to examine the a...

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    abstract::The extent of formation of solasodiene from solasodine upon treatment with hydrochloric acid under various conditions was determined. The diene formed was assayed by using the characteristic extinction at 236 nm. Diene formation was effected by the acid concentration and the boiling point of the solvent used. Optimal ...

    journal_title:Journal of pharmaceutical sciences

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    authors: Segal R,Breuer A,Milo-Goldzweig I

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  • Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging.

    abstract::Three dimensional terahertz pulsed imaging (TPI) was evaluated as a novel tool for the nondestructive characterization of different solid oral dosage forms. The time-domain reflection signal of coherent pulsed light in the far infrared was used to investigate film-coated tablets, sugar-coated tablets, multilayered con...

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  • "Predicting" Polymorphs of Pharmaceuticals Using Hydrogen Bond Propensities: Probenecid and Its Two Single-Crystal-to-Single-Crystal Phase Transitions.

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    journal_title:Journal of pharmaceutical sciences

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    authors: Engdahl A,Karlberg B,Thelander S

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    abstract::Because the ionized species is more polar than its un-ionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination...

    journal_title:Journal of pharmaceutical sciences

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    journal_title:Journal of pharmaceutical sciences

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    authors: El-Masry S,Korany MA,Abou-Donia AH

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Newman KD,Sosnowski DL,Kwon GS,Samuel J

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