Innovate combination of sevoflurane dilution in dimethyl sulfoxide: A stability study by gas chromatography and nuclear magnetic resonance

To investigate physicochemical stability of sevofuranein dimethyl sulfoxide using gas chromatography with a fame ionization detector and nuclear magnetic reso-nance （NMR）.METHODSUndiluted sevoflurane, plus dilutions 1：2, 1：5, 1：10, 1：25, and 1：50 in dimethyl sulfoxide were prepared in a vertical laminar fow cabinet class Ⅱ type B and stored at different temperatures （23 ℃, 6 ℃, and -10 ℃） for 45 d. Sterile 1 mL polypropylene amber syringes to minimize light degradation, caps and needles were used. The presence of sevofurane and its degradation products in the samples was determined by gas chroma-tography with flame ionization detector （260 ℃, 40min）, and by 1H, 19F, and proton-decoupled 19F nuclearmagnetic resonance.RESULTS The gas chromatography analysis showed sevofluraneand dimethyl sulfoxide （DMSO） retention times were 2.7and 13.0 min, respectively. Pure DMSO injection into thecolumn resulted in two additional peaks at 2.1 and 2.8min. The same sevofurane peak at 2.7 min was observedin all the dilutions at -10 ℃, 4 ℃ and 25 ℃. The NMRspectra showed signals consistent with the sevoflurane structure in all the dilutions at -10 ℃, 4 ℃ and 25 ℃. In the 1H spectrum, two signals corresponding to the sevoflurane molecule were observed at 5.12 and 4.16 parts per million （ppm5）. In the 19F-NMR spectrum, two signals were observed at -76.77 ppm and -157.13 ppm. In the 19F NMR CPD, two signals were observed at -76.77 ppm and -157.13 ppm. The first one showed a doublet （JF-F = 3.1 Hz） which integrated by six fluorine nuclei from the hexafluoro-isopropyl group. The second signal was integrated by a fuorine atom and showed a septuplet （JF-F = 3.1 Hz）.CONCLUSIONThis study shows that different concentrations ofsevofurane in dimethyl sulfoxide retain their chemicalcomposition after exposure to different temperaturesfor a period of 45 d.

Crystalline inclusion complexes formed between the drug diflunisal and block copolymers

The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.