| Objective: Used fiber-optic sensing technology apply to evaluate consistency of imitative drugs, establish dissolution determination of personalized drugs, such as cefuroxime axetil tablets, simvastatin tablets, perphenazine tablets of small specification, temperature sensitive phenytoin sodium tablets and diclofenac sodium and codeine phosphate tablets. Measured intrinsic dissolution rate of active pharmaceutical ingredient of two different crystal rifampicin, and combined dissolution and in-vivo intestinal absorption experiment, analysis the relationship between different intrinsic dissolution rate of two crystal rifampicin APIs and intestinal absorption curve. Adopted micro order flow injection analysis technology to establish method of calcein fluorescence quenching for rapidly measuring rifampin. Methods: 1. Refered to Chinese pharmacopoeia and CFDA principle of consistency evaluation of imitative drugs, measured dissolution curve of different manufacturers of cefuroxime axetil tablets in the four media, usd method of f2 similarity factor to evaluate consistency of dissolution curve. 2. Set up dissolution method of fiber-optic sensing monitoring simvastatin tablets. 3. Used dynamic multiplying factor to eliminate interference of excipient to dissolution of perphenazine tablets, adopted fiber optical chemical sensor real-time on-line monitoring dissolution and compare with Chinese pharmacopoeia. 4. Drew standard curve under the conditions of room temperature and 37 ℃ respectively and measured dissolution of phenytoin sodium tablets. 4. Established mathematical model which was based on dual-wavelength isosbestic point spectrophotometry, fiber-optic sensing real-time monitored dissolution process of diclofenac sodium and codeine phosphate tablets, obtained real-time dissolution curve of two ingredients and compared with HPLC. 6. Used fiber-optic sensing in-situ intrinsic drug dissolution analysis system, real-time monitored intrinsic dissolution of two different crystal rifampicin APIs in four media, calculated intrinsic dissolution rate, and evaluated the similarity by f2 similarity factor method. 7. Used fiber-optic sensing to determine open dissolution curve of two kinds of crystal rifampicin APIs in real-time, and adopted the peristaltic pump to inject dissolution liquid into four different intestinal segments of living rats, measured intestinal absorption curve by HPLC, and evaluated the similarity by method of f2 similarity factor. 8. Used micro order flow injection analysis technology, established method of calcein fluorescence quenching for determination of rifampicin. Results:1. The f2 factor of dissolution curve of cefuroxime axetil tablets of two manufacturers were 94, 91, 91 and 93 in four kinds media respectively. 2. In pH1.2 hydrochloric acid, dissolutions of simvastatin tablets in 30 minute between HPLC and FODT differed by 50%. 3. Contrasted dissolution data of perphenazine with method of Chinese pharmacopoeia and FODT, dissolution results were no statistical difference in 10, 17, 60 minute, the absolute error was 4.15%, 1.90% and 1.53% respectively. 4. Average error of standard curve of phenytoin sodium of room temperature and and 37 ℃ was 18.6%. 5. Dissolution of two components of diclofenac sodium and codeine phosphate tablet in 45 minute were greater than 75% conformed to the requirement of Chinese pharmacopoeia, compared cumulative dissolution with FODT and HPLC, there was no significant difference between them(p>0.05). 6. f2 factors of inherent dissolution curve of two kinds of crystal rifampicin APIs were 48, 30, 68 and 69 in the four kinds media respectively. 7. Absorption curve of two crystal rifampicin APIs measured by HPLC in four different intestinal segments of rats were completely different. 8. The luminous intensity of calcein was maximum when concentration of calcein was 33.33 μg·mL-1 in alkaline medium, under this condition, concentration of rifampicin in the range of 20.64 to 103.2 μg·mL-1 and intensity of calcein fluorescence quenching showed a good linear relationship, linear equation was Y=192.57X+44624(r=0.9997). Conclusion: 1. The dissolution curves of cefuroxime axetil tablets of two manufacturers in four kinds media were similar.2. Simvastatin tablets easy undergo hydrolysis under acid condition, FODT could not measure its real dissolution process in acidic medium, we should measure dissolution of simvastatin tablets by HPLC. 3. FODT could be used for rapidly release process analysis and dissolution of drugs of small specifications. 4. The temperature had influence on the absorbance of phenytoin sodium, standard curve should be drawing under the condition of 37 ℃. 5. Fibre-optic dissolution test system assisted by the mathematical separation model of linear equations was able to detect the dissolution of diclofenac sodium and codeine phosphate simultaneously and it could provide bicomponent dissolution process curve and complete dissolution data.6. Inherent dissolution process of two kinds of crystal rifampicin APIs had no similarity in the water and pH1.2 hydrochloric acid but similarly in pH4.5 and pH6.8 buffer salt.7. Absorption curves of two kinds of crystal rifampicin APIs had no similarity in four different intestinal segments of rats, the difference of APIs with different crystal forms had influence on the absorption in vivo. 8. The method of micro order flow injection with calcein fluorescence quenching was rapidly, accurately, well reproducibility, wide linear range and provided a new basis for determination of content of rifampicin. |
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