Abstract
The quality control of medicines guarantees the effectiveness of treatments for diseases. We explore the use of texture analysis of patterns in dried droplets as a tool to readily detect both impurities and changes in drug concentration. Four types of medicines associated with different routes of administration were analyzed: Methotrexate, Ciprofloxacin, Clonazepam, and Budesonide. We use NaCl and a hot substrate at 63 C to promote aggregate formation and to reduce droplet drying time. Depending on the medicine, optical microscopy reveals different complex aggregates such as circular to oval splatters, fern-like islands, crown shapes, crown needle-like and bump-like patterns as well as dendritic branched and star-like crystals. We use some physical features of the stains (as the stain diameter and superficial area) and gray level co-occurrence matrix (GLCM) to characterize patterns of dried droplets. Finally, we show that structural analysis of stains can achieve 95% accuracy in identifying medicines with 30% water dilution, while it achieves 99% accuracy in detecting drugs with 10% other substances.
Highlights
The quality control of medicines is carried out by using near-infrared (NIR) spectroscopy [1,2], Raman spectroscopy [3,4], chromatography [5,6,7] and X-ray fluorescence (XRF) spectrometry [8], among many others
We evaluated four types of commercial medicines associated with different routes of administration: Methotrexate, Ciprofloxacin, Clonazepam, and Budesonide
Dried droplets of Methotrexate/NaCl show dendritic branched crystallization patterns surrounded by a thin smooth coffee ring
Summary
The quality control of medicines is carried out by using near-infrared (NIR) spectroscopy [1,2], Raman spectroscopy [3,4], chromatography [5,6,7] and X-ray fluorescence (XRF) spectrometry [8], among many others. It is important to note that all these techniques are very effective but involve the use of sophisticated instrumentation and highly trained personnel, requiring careful and controlled conditions. In this investigation, we propose using the pattern left by an evaporated drop as a unique signature of each compound, unaltered or not. The analysis of patterns formed by droplet evaporation has already been used in many fields, such as diagnosis of pathologies [9,10,11], bioassays analysis, study of bacteria motility [12,13,14], detection of structural changes in liposomes [15], development of agricultural products [16,17,18], among many others [19,20,21,22,23,24,25]. The “coffee ring effect” as a Low-Cost tool has been used for the detection of protein mutation [27] and the estimation of β-sheet
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