(M1330-09-61) Homogenization Process Conditions Affect the Chemical Stability of Polysorbate 80 and Globule Size Distribution of Castor Oil Emulsion

Purpose: Polysorbate 80 (Tween 80) and polysorbate 20 (Tween 20) although abundantly used surfactants in small molecule and biologics formulations, are susceptible to hydrolysis & oxidation in aqueous environments. The purpose of this study was to investigate the effect of homogenization process conditions on the chemical stability of polysorbate 80 (PS-80) and globule size distribution of the castor oil emulsion.

Methods: An emulsion concentrate was prepared by adding a premix of PS-80 and castor oil to MilliQ water while mixing using a polytron rotor stator mixer starting at 2500 RPM for 5 minutes. The resultant emulsion concentrate was further processed at increasing speeds and duration of homogenization to obtain varied average globule size (Z_avg) profiles for the emulsions (F1 to F6). The finest Z_avg sample (F6) was obtained by additionally passing it through microfluidizer at ~25000 psi pressure. The resulting emulsion samples were diluted with MilliQ water and the pH was adjusted to 7.4 using 1N NaOH solution. Emulsions (F1 – F6) were filled into semipermeable LDPE plastic containers, stored at 60 ⁰C in a hot air oven, and sampled through 14 days at defined time intervals. After sampling at each time point, the samples were stored refrigerated and analyzed for PS-80 concentration by UPLC, and average globule size (Z_avg) by DLS. PS-80 solutions in MilliQ water and castor oil were used as controls.

Results: Significant loss of PS-80 assay was observed over the storage period proportional to the homogenization duration imparted for preparing the emulsions. An overall increase in the average globule size distribution (Z_avg) was observed for all the samples over the storage period. A peculiar phenomenon was observed for the samples that had bimodal globule size distribution, which converted to unimodal distribution over the storage period suggesting rearrangement of the emulsion globule populations as the surfactant loss proceeded in the samples over the storage period.

Conclusion: Homogenization time during formulation affected the chemical stability of PS­80 and the globule size distribution profile of the PS-80/castor oil emulsion over the monitored stability period. Appropriate formulation and/or process controls are needed to address potential deleterious effects on the chemical and physical properties of PS-80 and castor oil emulsion. Future studies will be aimed at investigating the formulation & process controls needed to minimize the potential PS-80 loss.

Acknowledgements: Anand Ubhe, Mouy Chea, and Alex Huscroft are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.

Tables 1, 2, & 3

Figures 1, 2, & 3

Figures 4, 5, & 6