Solid-state NMR investigation of indomethacin-cyclodextrin complexes in PEG 6000 carrier.
Various solid dispersions of alpha-, beta- and gamma-cyclodextrin (CD) in PEG 6000 with and without the addition of 5% w/w indomethacin were prepared by the melting method using the original components. The samples were investigated by solid-state (13)C NMR, and the interactions between the drug and the cyclodextrins were evaluated. The indomethacin-gamma-CD phase with tetragonal symmetry found in a previous X-ray study gave chemical shifts which suggested that this phase is a complex between indomethacin and gamma-CD. Evidence of an indomethacin-beta-CD complex were found. A distribution of the chemical shifts for beta-CD was attributed to the possible formation of different types of complexes between indomethacin and beta-CD. No complex formation was found in the alpha-CD system. The degree of relative crystallinity of the samples in the gamma-CD system was measured by (1)H NMR, X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and modulated-temperature DSC (MTDSC). The results obtained by the NMR, XRD, and DSC techniques showed that the dispersions were less crystalline than the pure polymer carrier, and the dispersion containing the indomethacin-gamma-CD complex had the lowest degree of crystallinity. By the MTDSC method a deviation was found for the PEG 6000/indomethacin dispersion. This emphasizes that the different techniques give specific information on the crystallinity.
Wulff
Marie
M
Department of Physical and Inorganic Pharmaceutical Chemistry, Box 580, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden.
Aldén
Maggie
M
Tegenfeldt
Jörgen
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002247:Carbon Isotopes / Q000737:chemistry; D003460:Crystallization; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002247:Carbon Isotopes; D003505:Cyclodextrins; D004337:Drug Carriers; D011092:Polyethylene Glycols; D006859:Hydrogen; D007213:Indomethacin