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The method of homogeneity evaluation for active pharmaceutical ingredient (API) spatial distribution in lyophilized product was investigated for the first time with confocal micro-Raman spectroscopy mapping, using pemetrexed disodium for injection as a model drug. Certain areas of the lyophilized product were scanned to obtain Raman spectra. The classical method ("peak clipping" method) was employed for mapping with characteristic Raman peaks of the API and the excipient. Due to the API being finely dispersed in the excipient in lyophilized products, the classical method cannot discriminate between the two ingredients making the distribution homogeneity difficult to evaluate. The "ratio of characteristic peak intensities" method was then utilized. Using this method, the relative intensity of the characteristic Raman peaks of the API to the excipient was applied for mapping and the relative content of API to excipient was calculated for a homogeneity evaluation of the drug distribution. The validation of this method showed a good linear relationship between the relative intensity and the relative content of API to excipient (r2 > 0.99), and the precision and recovery were adequate for homogeneity evaluation of API by Raman spectroscopy mapping. Five products of pemetrexed disodium for injection from different manufacturers were tested through Raman maps applying this method and the histograms of relative Raman intensity were also plotted by frequency to help the homogeneity evaluation of drug distribution. The results showed that there were obvious differences in the drug distribution homogeneity from different products, where a more homogeneous API distribution was found in the brand product. This research provides a reliable method for the homogeneity evaluation of API distribution, which facilitates quality evaluation and process optimization of lyophilized products.
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ABSTRACT OBJECTIVE：To establish a method for simultaneous determination of 8 components in the lyophilized product of Chaihu shugan san decoction. METHODS：UPLC method was adopted to determine the contents of albiflorin，paeoniflorin，ferulic acid，naringin，hesperidin，benzoyl paeoniflorin，glycyrrhizic acid and α-cyperone in 6 batches of lyophilized product of Chaihu shugan san decoction. The determination was performed on Phenomenex column with mobile phase consisted of 0.1％ formic acid water-acetonitrile at the flow rate of 1 mL/min，the sample volume was 10 μL. The detection wavelength was set at 250 nm，and column temperature was 30 ℃. RESULTS：The linear range of albiflorin，paeoniflorin，ferulic acid，naringin，hesperidin，benzoyl paeoniflorin，glycyrrhizic acid and α-cyperone were 3.606-8.414，23.988-55.972，1.218-2.842，35.964-83.916，12.009-28.021， 1.194-2.786，3.609-8.421，5.294-12.352 μg/mL，respectively（r＝0.999 5-0.999 9）. The limits of quantitation were 0.206，0.178， 0.256，0.168，0.196，0.242，0.268，0.157 μg/mL，respectively. RSDs of precision，stability（12 h）and repeatability tests were all lower than 2％（n＝5 or 6）；the recoveries were 97.93％，98.18％，96.57％，97.61％，98.51％，97.45％，98.14％，96.91％（all RSD＜2％ ）. The average contents of albiflorin， paeoniflorin， ferulic acid， naringin， hesperidin， benzoyl guanosine， and glycyrrhizic acid in 6 batches of samples were 59.258，429.237，23.173，625.847，200.424，15.048，67.620 μg/g，respectively. α-cyperone was not detected because of its volatility. CONCLUSIONS：The method is simple，stable，reliable and accurate. It could provide reference for quality control of the lyophilized product of Chaihu shugan san decoction
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OBJECTIVE:To prepare nattokinase immunoliposomes and its lyophilized product and to evaluate its pharmaceutical quality. METHODS: Nattokinse liposomes were prepared by film dispersion method, then the immunoliposomes were prepared by carbodiimide method coupled anti-human fibrin D-dimer monoclone antibody SZ-63 and lyophilized and evaluated about its pharmaceutical quality. RESULTS: Lyophilized immunoliposomes were multilamellar vesicles with its mean diameter, Zeta potentials at 251.6 nm, —34.6 mV, respectively. The lyophilized product of nattokinase immunoliposomes exhibited good appearance and satisfactory redispersibility, with its loss on drying at 14.30% and critical relative humidity at 45.66%. CONCLUSION: Nattokinase immunoliposomes and its lyophilized product have been prepared successfully.