title: Impact of inter- and intramolecular interactions on the physical stability of indomethacin dispersed in acetylated saccharides.
abstract: Differential scanning calorimetry (DSC), broadband dielectric (BDS), and Fourier transform infrared (FTIR) spectroscopies as well as theoretical computations were applied to investigate inter- and intramolecular interactions between the active pharmaceutical ingredient (API) indomethacin (IMC) and a series of acetylated saccharides. It was found that solid dispersions formed by modified glucose and IMC are the least physically stable of all studied samples. Dielectric measurements showed that this finding is related to neither the global nor local mobility, as the two were fairly similar. On the other hand, combined studies with the use of density functional theory (DFT) and FTIR methods indicated that, in contrast to acetylated glucose, modified disaccharides (maltose and sucrose) interact strongly with indomethacin. As a result, internal H-bonds between IMC molecules become very weak or are eventually broken. Simultaneously, strong H-bonds between the matrix and API are formed. This observation was used to explain the physical stability of the investigated solid dispersions. Finally, solubility measurements revealed that the solubility of IMC can be enhanced by the use of acetylated carbohydrates, although the observed improvement is marginal due to strong interactions.
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Department of Pharmacognosy and Phytochemistry, Medical University of Silesia in Katowice , ul. Jagiellonska 4, 41-200 Sosnowiec, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Kaminska
authors.forename: K
authors.initials: K
authors.lastname: Adrjanowicz
authors.forename: M
authors.initials: M
authors.lastname: Tarnacka
authors.forename: K
authors.initials: K
authors.lastname: Kolodziejczyk
authors.forename: M
authors.initials: M
authors.lastname: Dulski
authors.forename: E U
authors.initials: EU
authors.lastname: Mapesa
authors.forename: D
authors.initials: D
authors.lastname: Zakowiecki
authors.forename: L
authors.initials: L
authors.lastname: Hawelek
authors.forename: I
authors.initials: I
authors.lastname: Kaczmarczyk-Sedlak
authors.forename: K
authors.initials: K
authors.lastname: Kaminski
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002152:Calorimetry, Differential Scanning; D004355:Drug Stability; D041981:Gastrointestinal Tract / Q000473:pathology; D005898:Glass; D006801:Humans; D006860:Hydrogen Bonding; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry*; D008320:Maltose / Q000737:chemistry*; D008968:Molecular Conformation; D012995:Solubility; D013053:Spectrophotometry; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013395:Sucrose / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D001786:Blood Glucose; D013395:Sucrose; D008320:Maltose; D007213:Indomethacin