Comparative Assessment of Levodopa and Carbidopa Cleanability from Stainless Steel Surfaces: A Risk-Based Approach for Pharmaceutical Cleaning Validation
Year: 2025
Type: article
Abstract: 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.
Authors: Patel, Birju, Patel, Jayminkumar
Institution: Anika Therapeutics (United States)
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
OpenAlex ID: W7108924916
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