Cleaning verification: Exploring the effect of the cleanliness of stainless steel surface on sample recovery.

The parameters affecting the recovery of pharmaceutical residues from the surface of stainless steel coupons for quantitative cleaning verification method development have been studied, including active pharmaceutical ingredient (API) level, spiking procedure, API/excipient ratio, analyst-to-analyst variability, inter-day variability, and cleaning procedure of the coupons. The lack of a well-defined procedure that consistently cleaned coupon surface was identified as the major contributor to low and variable recoveries. Assessment of acid, base, and oxidant washes, as well as the order of treatment, showed that a base-water-acid-water-oxidizer-water wash procedure resulted in consistent, accurate spiked recovery (>90%) and reproducible results (Srel≤4%). By applying this cleaning procedure to the previously used coupons that failed the cleaning acceptance criteria, multiple analysts were able to obtain consistent recoveries from day-to-day for different APIs, and API/excipient ratios at various spike levels. We successfully applied our approach for cleaning verification of small molecules (MW<1000Da) as well as large biomolecules (MW up to 50,000Da). Method robustness was greatly influenced by the sample preparation procedure, especially for analyses using total organic carbon (TOC) determination.

Functional assessment of a washing emulsion for sensitive skin: mild impairment of stratum corneum hydration, pH, barrier function, lipid content, integrity and cohesion in a controlled washing test.

BACKGROUND/PURPOSE: Sensitive skin has been described as a skin type with higher reactivity than normal skin and exaggerated reactions to external irritants. Washing with soaps is harmful for barrier-related parameters. Cutaneous irritation induced by cleansing products under exaggerated test conditions, e.g. patch testing, is not necessarily predictive of the irritation occurring under standardized daily use conditions. The purpose of the study was to assess the effect of an improved washing solution for sensitive skin in a half-site comparison on barrier-related parameters. METHODS: Thirty healthy volunteers with self-reported sensitive and so-called problematic skin performed standardized washings with a soap-free washing emulsion with mild acidity (pH 5.5) for 3 weeks. Test areas were both forearms and the cheek. Non-invasive biophysical measurements of the following skin parameters, epidermal permeability barrier function measured as transepidermal water loss (TEWL), stratum corneum (SC) hydration, pH value, skin surface lipids, skin temperature and SC integrity/cohesion, were assessed prior to the first washing, on days 7, 14 and 21 after beginning the washing procedure. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. SC integrity was quantified by measuring TEWL after sequential stripping with D-Squame tapes. RESULTS: The use of the washing emulsion led to a mild damage of the epidermal permeability barrier function with no marked difference to water application. Furthermore, a mild but significant dehydration was assessed after 21 days vs. baseline without any differences between the water-treated and the washing emulsion-treated forearm. On the cheek no dehydration was detectable but the lipid content was reduced under the washing emulsion. The pH value increased in all three test areas after 21 days, again without significant differences between water and the washing solution. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. The SC cohesion decreased after 21 days on the water-treated as well as on the washing emulsion-treated arm. The decrease over time was significant when used the optical spectroscopy measuring. A standardized questionnaire revealed positive characteristics of the washing emulsion and good acceptance. CONCLUSION: The investigated standardized washing model with the endpoints epidermal barrier function, SC hydration, surface pH, skin surface lipids, skin temperature and SC integrity/cohesion showed only mild damage comparable to washing with water.