Title : Nonlinear optical characterization as a non-destructive tool for photostability and packaging assessment in liquid pharmaceuticals: A vitamin D3 model study

High-Performance Liquid Chromatography (HPLC) remains the gold standard for liquid pharmaceutical analysis but is destructive and incompatible with real-time screening. This study evaluates the single-beam Z-scan technique as a rapid, non-destructive quality control (QC) tool, using photosensitive cholecalciferol (Vitamin D?) injections as a model. Samples were assessed under three conditions: unexposed (baseline), sunlight-exposed in sealed ampoules, and sunlight-exposed after transfer to clinical syringes. Nonlinear optical (NLO) profiling employed a closed-aperture Z-scan with a 655 nm CW diode laser (35–172 mW). Characteristic peak-to-valley traces emerged above 140 mW, confirming measurable third-order nonlinear responses. Analysis identified a distinct nonlinear threshold (P??) and pronounced high-power profile variations, establishing a quantitative framework for non-destructive QC. Photoexposure triggered a dramatic collapse of the NLO signature, providing a highly sensitive photodegradation indicator. The nonlinear refractive index (n?) decreased progressively with exposure duration and handling: from 5.72×10?¹? cm²/W (unexposed) to 1.01×10?¹? and 1.19×10?¹? cm²/W (ampoule, 1 and 3 days), and further to 2.51×10?¹¹ and 6.74×10?¹¹ cm²/W (syringe, 1 and 3 days).  This order-of-magnitude reduction demonstrates the technique’s sensitivity to both degradation extent and syringe-induced destabilization. While these findings validate Z-scan as a rapid, non-destructive screening tool, rigorous systematic studies are required to fully establish NLO parameters as reliable, standardized metrics for routine pharmaceutical QC.

Arafath Ahmed Marshed is a physics graduate from Bangladesh whose master’s thesis research focused on nonlinear optical characterization for non-destructive quality control of liquid pharmaceuticals. He continues to advance this work by mentoring undergraduate students in Z-scan-based photostability screening and optical profiling of drug formulations. His research interests lie at the intersection of photonics, analytical chemistry, and biomedical optics, with a strong commitment to translating novel optical techniques into practical pharmaceutical quality assurance tools. He is actively seeking research opportunities to pursue a career in biomedical optics and translational analytical sciences.