Comparative Assessment of Levodopa and Carbidopa Cleanability from Stainless Steel Surfaces: A Risk-Based Approach for Pharmaceutical Cleaning Validation

Background: Cleaning validation represents a critical component of pharmaceutical quality assurance, requiring scientific evidence that manufacturing equipment can be consistently cleaned to predetermined acceptance criteria. The selection of worst-case products for validation studies necessitates comparative cleanability assessments based on physicochemical properties and empirical data.

Objective: To systematically evaluate and compare the cleanability profiles of Levodopa and Carbidopa from stainless steel surfaces using multiple cleaning methodologies, establishing a scientifically justified worst-case product for cleaning validation protocols.

Methods: Stainless steel coupons (316L, 50×50mm) were contaminated with 1000 μg of each compound and subjected to three cleaning procedures: purified water submersion, 0.1N sodium hydroxide solution, and 1% detergent solution, each with 2-minute contact time. Residual contamination was quantified using validated HPLC-UV methodology with swab sampling. Statistical analysis included two-sample t-tests and effect size calculations (Cohen's d).

Results: Water cleaning demonstrated significant differences in removal efficiency between Levodopa (93.00±0.14%) and Carbidopa (86.05±0.21%; p=0.0012, Cohen's d=40.83). Alkaline cleaning improved both compounds' removal (Levodopa: 99.58±0.04%, Carbidopa: 98.25±0.07%; p=0.0018), while detergent achieved optimal cleaning (>99.6% for both). Carbidopa consistently exhibited lower cleanability across all methods, with residuals exceeding acceptance limits (10 μg/coupon) under water-only cleaning (138-141 μg/coupon).

Conclusions: Carbidopa represents the worst-case product for cleaning validation due to significantly lower removal efficiency, attributed to its reduced aqueous solubility (0.2 mg/mL versus 2.0 mg/mL for Levodopa). These findings support risk-based cleaning validation approaches and emphasize the necessity of alkaline or detergent-based cleaning for adequate contamination control in multi-product facilities.