Browsing by Subject "aqueous solubility"

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    Crystal engineering of salts and cyclodextrin inclusion complexes of selected medicinal agents
    (2026) Pietrobelli, Erica; Caira, Mino; Bacchi, Alessia
    The objective of this study was to improve the aqueous solubility of four active pharmaceutical ingredients (APIs), namely droperidol, tolfenamic acid, loratadine and 5methoxy-1H-indole-2-carboxylic acid via supramolecular derivatization. The main techniques employed were co-crystallization and cyclodextrin inclusion complexation. All isolated products were characterised using powder X-ray diffraction (PXRD), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). When a single crystal was obtained, it was characterized with single-crystal X-ray diffraction (SCXRD). Co-crystallization was attempted for each API in combination with different “generally recognized as safe” (GRAS) coformers to form co-crystals. Liquid-assisted grinding (LAG) and co-precipitation experiments involving droperidol and loratadine were generally unproductive due to their intractable nature, while tolfenamic acid was tractable but showed no affinity for co-crystallization. On the other hand, the experiments with MICA (5-methoxy-1H-indole-2-carboxylic acid) resulted in the successful synthesis and characterisation of salts with isonicotinamide and piperazine, with a MICA:coformer 2:1 molar ratio in both cases. Cyclodextrin (CD) inclusion complexation of the APIs was studied with β-CD, γ-CD and dimethylated β-CD (DIMEB). The complexation attempts yielded an inclusion complex between DIMEB and loratadine. A single crystal was isolated, and its crystal structure was determined. The general structural features of a new β-CD inclusion complex of MICA were deduced using PXRD in the absence of suitable crystals for SCXRD by establishing isostructurality of its host assembly with that of a series of known CD complexes. Phase solubility studies of MICA were carried out in aqueous medium using β-CD, γ-CD, hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated β-cyclodextrin (RAMEB) and sulfobutyl ether β-cyclodextrin sodium salt (SeβCD). The stability constants of the resulting complexes were estimated, and solubility improvement of MICA was recorded. RAMEB produced the greatest solubility enhancement of MICA by a factor of ~11 at the highest CD concentration employed.