Stabilization of drug droplet contact line via Bovine Serum Albumin Solution-Phase Additive

Abstract

The method of pattern analysis in dried droplets has emerged as an effective tool for detecting adulterants in medications and diagnosing pathologies. However, despite numerous studies on the drying dynamics of droplets, there remains a need for effective methods to stabilize droplet contact line and achieve controlled coating. Finding alternative solutions for droplet stabilization could significantly improve the precision and efficacy in the application of the dry droplet pattern recognition method. In this study, we hypothesize that bovine serum albumin (BSA) can act as an effective tool for stabilizing the contact line of sessile methotrexate (MTX) drops, controlling pattern formation during the drying process. We evaluated BSA concentrations of 0.01, 0.1, 0.25, 0.5, 1, and 2% in MTX (10%) solutions; which, in the absence of BSA, become destabilized on polymethylmethacrylate (PMMA) substrates. Our results indicate that, starting from a concentration of 0.1% BSA, the methotrexate droplets are efficiently fixed, producing highly reproducible patterns. Using measurements of height profile, contact angle, and evaporation time, we found that BSA fixes the droplets and prevents the deformation of the contact line. Additionally, we observed that BSA modifies the interaction between the droplet and the substrate, improving adhesion and reducing the expansion or contraction of the droplets. Importantly, the stabilizing effect was only observed when BSA was present in solution; when BSA was pre-adsorbed onto the substrate, MTX droplets exhibited spreading and destabilization. We demonstrated that BSA promotes a homogeneous distribution of solutes and more uniform and controlled evaporation when acting as a solution-phase additive in MTX formulations. These findings indicate that BSA can serve as a functional modulator for enhancing reproducibility and controlling deposition in dropwise manufacturing of pharmaceutical coatings.