In recent decades, the design of cocrystals has developed significantly due to the unique characteristics and advantages of cocrystals, which help to improve the physicochemical properties of drugs, especially solubility. Zwitterions are attractive and interesting co-formers. However, the physicochemical properties of cocrystals with zwitterionic co-formers, i.e. zwitterionic cocrystals, have not been adequately evaluated. In this study, solid-state characterization of a newly developed zwitterionic cocrystal of diclofenac (DFA), a non-steroidal antiinflammatory drug, and the amino acid L-proline (PRO) was performed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction (PXRD) analyses. In addition, the crystal structure of the cocrystal (DFA-PRO) was determined by single-crystal X-ray diffraction analysis, after which the zwitterionic structure was confirmed. The cocrystallization during co-grinding, which was investigated by PXRD, followed first-order kinetics. Furthermore, the solubility of the zwitterionic cocrystals was 7.5-times higher than that of the DFA crystals. The results indicate that the cocrystal is stable under ambient conditions; however, it hydrates and transforms into a mixture of L-proline monohydrate crystals and DFA crystals under conditions of high humidity.

Meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin sulfonate (TDMPzP), a water-soluble porphyrin derivative, was synthesized and used as a colorimetric reagent for Cu detection on a microfluidic paper-based analytical device (µPAD) using distance-based quantification. TDMPzP showed a high selectivity for Cu detection in aqueous solutions. When Cu was added to the TDMPzP under acidic conditions, a color change from green to a pink was observed by the naked eye. Under optimized conditions, the application of this system to a distance-based μPAD exhibited good analytical response. The presence of common metal ions (Al, Fe, Mg, Co, Mn, Zn, Pb, Cd, Sn, and Ni) did not interfere with Cu detection within reasonable tolerance ratios. The lowest concentration of copper that could be measured was 1mgL (1ppm) which meets the requirements for drinking water contamination regulations from the US Environmental Protection Agency (EPA) and World Health Organization (WHO) guidelines for drinking water. Real drinking water samples were analyzed to confirm the practical application of this system and the results showed good agreement with ICP-MS data. This distance-based µPAD based on TDMPzP for Cu detection is convenient and effective for real-time drinking water analysis.

Glibenclamide is a second-generation sulfonylurea drugs for treatment of diabetes mellitus. Up to now, a glibenclamide imprinted polymer is not reported for molecular recognition in biological samples. This research is conducted to have Molecular Imprinted Solid Phase Extraction (MISPE) for separation of glibenclamide from serum samples. The results showed that the itaconic acid is the functional monomer that provides the best interaction with the template (glibenclamide) from the computational study using Gaussian 09 software. The MISPE made from itaconic acid monomer at a ratio of 1:6:70 gives the best binding to glibenclamide in methanol pH 4. Serum sample which was spiked with glibenclamide gives recovery more than 80% after pretreatment with MISPE 2 in all concentration ranges. Selectivity test showed that MISPE 2 can be used for selective extraction of glibenclamide from serum samples spiked with other sulfonylurea drugs. This developed MISPE could be further used as extraction method in antidiabetic drugs analysis from biological samples.

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Recently, solid-state engineering has become a promising approach to improving the stability and potency of antibiotics. Levofloxacin (LF) is a broad-spectrum fluoroquinolone antibiotic marketed in solid and solution dosage forms. However, this substance forms solid hydrates under ambient conditions and degrades due to lighting, which may change its solid properties and dose. In addition, resistance cases have been reported due to long-time antibiotic usage. This research aims to allow LF to react with antioxidant dihydroxybenzoic acid (DHBA), which has low antimicrobial activity, to produce a more stable compound under water and lighting conditions and improve LF’s potency. The experiment begins with a screening to select potential DHBA isomers that can react with LF and predict the stoichiometric ratio using phase diagrams, which show that 2,6-DHBA and 3,5-DHBA are prospective antioxidants that can react with LF in a (1:1) molar ratio. Multicomponent systems are prepared by dissolving the LF–DHBA mixture in (1:1) ethanol–methanol (95% grade) and evaporating it. Then, the new solid phase formation is confirmed by thermal analysis and powder X-ray diffractometry. Next, infrared spectrophotometry and neutron magnetic resonance analyses are used to identify the LF–DHBA’s interactions. Finally, single-crystal X-ray diffractometry is used to solve the three-dimensional structure of the multicomponent system. We then conduct a hygroscopicity and stability test followed by a lighting and potency test using the microdilution method. Our data reveal that both reactions produce salts, which are named LF-26 and LF-35, respectively. Structurally, LF-26 is found in an anhydrous form with a triclinic crystal packing, while LF-35 is a hemihydrate in a monoclinic system. Afterward, both salts are proven more stable regarding water adsorption and UV lighting than LF. Finally, both multicomponent systems have an approximately two-fold higher antibiotic potency than LF. LF-26 and LF-35 are suitable for further development in solid and liquid dosage formulations, especially LF-35, which has superior stability compared with LF-26.