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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 29 with surfactants had the highest leachable silicone oil amounts. The leachable silicone oil analysis results for the formulations with different pH are summarized in Table X. The data show that the pH of the formulations had a significant impact on the amount of leachable silicone oil. The 8.2 pH formulation had significantly more leachable silicone oil than the 5.0 pH formulation. There may be several reasons for the pH impact on the leachable silicone oil amounts. First, the bonding between glass and silicone oil molecules is attributed to the cross linking of polydimethylsiloxane to silanol groups on the glass surface (7), including hydrogen bonding between glass silanol and electronegative oxygen of polydimethylsiloxane. A higher pH may weaken the hydrogen bonding and make the silicone oil more prone to leach into the formulation. Second, pH may affect the degradation of silicone oil, espe- cially breakdown of the end group to trimethylsilanol. The exact cause of the pH effect on the amount of leachable silicone oil will require further study. The data also indicated that storage temperature had significant impact on the amount of leachable sili- cone oil. For example, 40 °C storage samples typically had more leachable silicone oil compared to 5 °C and 25 °C, consistent with the results in previous sections. Conclusion ICP–OES is a suitable technique for the analysis of leachable silicone oil in biopharmaceutical formula- tions. Leachable silicone oil in aqueous formulations requires further sample preparation to extract the leachable silicone oil from aqueous biopharmaceuti- cal formulations into organic solvents by liquid/liquid extraction or solid-phase extraction. There is a low risk of silicone oil leaching into a typical biopharmaceutical formulation as long as the formulation does not contain a co-solvent or surfactant. The risk increases if the formulation contains a co-solvent or surfactant. Surfactant is the most critical ingredient affecting the amount of leachable silicone oil, while formulation pH and storage temperature also have an impact. Overall, however, the amount of leachable silicone oil rep- resents only a small portion of the total silicone oil coated on prefilled syringes. References 1. E.J. Smith, J Parent Sci Tech 42 (4) S3–S13 (1988). 2. J.D. Andrade, Surface and Interfacial Aspects of Biomedical Polymers: Vol. 2: Protein Adsorption (Plenum Press, New York, NY, 1985). 3. L.S. Jones, A. Kaufmann, C.R. Middaugh, J Pharm Sci. 94 (4) 918–927 (2005). 4. A.S. Rosenberg, AAPS J 8 (3) E501–E507 (2006). 5. D. Wood et al., BioPharm International 23 (4) 26–36 (2010). 6. Clearco, "Introduction to Silicone Fluids," www.clearcoproducts.com/ introduction-to-silicone-fluids.html, Sep. 23, 2018. 7. N. Dixit, "Investigation of Factors Affecting Protein-Silicone Oil In- teractions," Doctoral Dissertation (University of Connecticut, 2013). PT Table VIII. Leachable silicone oil in formulations with co-solvent. Formulations Propylene glycol% 5 °C 25 °C 40 °C 1 0 0 0 0 2 1 0.3 0.4 0.5 3 2 0.4 0.2 0.1 4 5 0.6 0.2 0.9 5 10 0.3 0.7 0.8 Table IX. Leachable silicone oil in formulations with surfactant. Formulations Polysorbate 80% 5 °C 25 °C 40 °C 1 0 0 0 0 8 0.05 0.2 0.2 0.7 9 0.1 0.2 0.2 2.1 10 0.5 0.5 0.3 1.0 11 1.0 0.2 1.4 1.6 Table X. Leachable silicone oil in formulations of different pH. Formulations pH 5 °C 25 °C 40 °C 12 5.0 0 0.4 0.3 11 6.8 0.2 1.4 1.6 13 8.2 0.4 1.9 2.1