(W1030-08-54) Setting the Benchmark: Enhanced Purification of Polyoxyl 35 Castor Oil Using a Novel In-House Adsorbent System

Purpose: Polyoxyl 35 Castor Oil (PEG-35 castor oil) is a widely used nonionic surfactant and solubilizer in injectable formulations, notably in Paclitaxel, a poorly water-soluble chemotherapeutic agent. In such formulations, PEG-35 castor oil may comprise over 50% of the excipient volume. Its function is critical for improving drug solubility, stability, and dispersion. However, variability in visual appearance—especially color—remains a persistent concern due to differences in raw materials, oxidative degradation, or incomplete purification. For parenteral oncology products, even slight deviations in excipient color can raise regulatory concerns or affect patient perception. Regulatory guidelines require a UV absorbance ≤0.05 at 425 nm for injectable drug products, making excipient consistency crucial. This study aimed to develop and validate a robust, scalable purification process using an in-house optimized adsorbent blend. The goal was to minimize color in PEG-35 castor oil to well within regulatory limits, without compromising its functional properties. Additionally, the study evaluated the impact of the purified excipient on Paclitaxel solubility and stability under accelerated conditions.

Methods: Crude PEG-35 castor oil was purified using a proprietary combination of activated carbon, bentonite, and silicates. The adsorbent system was optimized to maximize color removal under ambient conditions, avoiding chemical bleaches or oxidants. Paclitaxel formulations (6 mg/mL) were prepared using both the purified and a commercial PEG-35 castor oil. Visual clarity and color intensity were evaluated by UV-Vis spectrophotometry at 425 nm and 430 nm across ≥3 batches to assess consistency. To evaluate functional equivalence, the saturation solubility of Paclitaxel (10 mg) in the purified excipient was determined using a thermodynamic equilibrium method, followed by HPLC-UV/PDA analysis. Accelerated stability testing was performed at 40°C / 75% RH over 12 weeks. Drug recovery from formulations using both excipient types was quantified at 0, 4, 8, and 12 weeks to evaluate stability under stress.

Results: The in-house purification process significantly lowered UV absorbance of PEG-35 castor oil to an average of 0.0198 at 425 nm—well below the 0.05 regulatory threshold. Commercial PEG-35 castor oil showed higher absorbance at 0.0432. When used in Paclitaxel formulations, the purified excipient yielded a formulation absorbance of 0.0233, compared to 0.0350 for the commercial counterpart. These findings reflect substantial improvement in visual clarity and consistency. Color reduction correlated directly with increasing activated carbon content in the adsorbent matrix, confirming its key role in eliminating color-contributing species. The process maintained the excipient’s chemical structure and viscosity, as no aggressive treatments were used. Paclitaxel solubility remained comparable between purified and commercial excipients, confirming retention of the surfactant’s core function. This validates that the purification process does not impair solubilization capacity. Accelerated stability studies revealed strong chemical robustness of formulations prepared with the purified excipient. Paclitaxel recovery remained at 100% at baseline, 99.8% at 8 weeks, and 99.6% at 12 weeks. In comparison, formulations with the commercial excipient showed a slightly greater decline to 99.1% by week 12. This suggests that the purified PEG-35 castor oil may confer improved chemical stability over time under stress conditions. Collectively, the results demonstrate that the in-house purification process consistently delivers pharmaceutical-grade PEG-35 castor oil with superior optical clarity, minimized color variability, and maintained functional performance. The solvent-free process is practical for industrial adoption and scale-up.

Conclusion: This study establishes a validated, scalable adsorbent-based purification platform that significantly enhances the visual quality of PEG-35 castor oil without compromising its functional properties. The process achieves UV absorbance values well below regulatory thresholds and ensures improved batch-to-batch consistency. The purified excipient retains its ability to solubilize Paclitaxel and supports formulation stability under accelerated conditions. Drug recovery remained >99.5% over 12 weeks, indicating that the process may also contribute to long-term chemical robustness. In summary, this novel purification approach offers pharmaceutical manufacturers a reliable solution for producing high-purity, visually consistent PEG-35 castor oil. It supports regulatory compliance, reduces batch rejections, and enhances quality in parenteral drug development, particularly in oncology applications.

Table 1. UV absorbance (425 nm) – PEG 35 castor oil and finished formulations.

Figure 1. Progressive reduction in PEG-35 castor oil color with increasing proportions of activated carbon in the adsorbent blend.

Figure 2. Saturation solubility of Paclitaxel in purified PEG-35 castor oil, confirming functionality is retained post-purification.