Erythromycin enteric-coated tablets to Release Study on
【Abstract】 Objective to erythromycin enteric-coated tablets
release rate determination of three methods for systematic study and comparison, and to establish its optimal
determination. Method of accounting for tons of hydrogen were used mouth alcohol chromogenic method, sulfuric acid color method, as well as high-performance liquid chromatography to erythromycin enteric-coated tablets release rate, for each
method to the study methodology and validation. The results using three methods may accurately determine the manner of the release rate of erythromycin enteric-coated tablets, the
results measured in different ways with little difference. Conclusion sulfuric acid color method for reagent easy to get, easy to operate, fast, accurate, as the best determination.
Key words Dirithromycin
Study on methods for the release determination of dirithromycin enteric ? coated tablets
ABSTRACT Objective Three methods by which the release of dirithromycin enteric-coated tablets were determinated and compared. Methods Xanthydrol coloring method, sulfuric acid
coloring method, and HPLC method were developed for determination of the release of dirithromycin enteric-coated
tablets. Result All of these methods can be used to determine the samples precisely, and difference of the results among
them is slightly. Conclusion Sulfuric acid coloring method is inexpensive, simple, rapid and precise, and it is regarded as the optimal method.
KEY WORDS Dirithromycin; Enteric-coated tablets; Release
Dirithromycin (dirithromycin) is a new type of second-
generation macrolide antibiotic erythromycin from erythromycin ring amine and fatty acid aldehyde condensation formed. Dirithromycin peptides by blocking the process of transfer of bacteria, inhibiting bacterial protein synthesis. In vitro of
erythromycin on the clinical evidence in a variety of common pathogenic bacteria have antibacterial effect. To erythromycin and erythromycin with a similar antibacterial spectrum, which is characterized by an excellent pharmacokinetic properties, half-life of up to 20 ~ 50h, adverse reactions are relatively mild [1,2]. Lilly's products in the United States in September 1993 in Spain, listed by the U.S. FDA approval in 1996, and income the United States Pharmacopoeia USP23. Currently there are several developed to erythromycin enteric-coated tablets
and enteric-coated capsules produced and approved for clinical use. Erythromycin enteric-coated tablets for the land release
rate determination method, the United States Pharmacopoeia (USP23) in the mouth accounted for tons of hydrogen used
alcohol chromogenic method ; China's pilot drug standards using sulfuric acid color method; In addition, you can also using the HPLC assay method for determination of drug release . We have these three methods were carried out
methodological studies, and the results measured by three methods were compared.
An instrument and reagent
ZRS-8 Intelligent Dissolution Tester (Tianjin University Radio Factory); Shimadzu UV-2401PC UV - visible
spectrophotometer; Shi-madzu high-performance liquid
chromatography (LC-10ATvp pump, SPD-10Avp visible UV detection
device, SCL-10Avp controller); AE200 electronic balance (Mettler - Toledo Instruments Shanghai Co., Ltd.).
Dirithromycin reference substance (purity 99.83%) was made by the Chinese pharmaceutical and biological products calibration; to erythromycin enteric-coated tablets (Size:
0.25g) as a self-made products; 10% of the population
accounted for tons of hydrogen to buy alcohol methanol
solution Since the Beijing Hengye Zhongyuan Chemical Co., Ltd.; acetonitrile, methanol for chromatography pure; hydrochloric acid, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium hydroxide and sulfuric acid were of
2 Methods and Results
Alcohol accounted for 2.1 tons of hydrogen chromogenic method
Accounted for tons of hydrogen in the use of mouth alcohol chromogenic determination of the process of this product release rate found in full accordance with USP23 in
the color conditions, methods of linear and poor tolerability; improved color conditions, can method has more good linearity and color stability. Other conditions, such as the concentration of reference substance solution and the
detection wavelength, etc. are in the same conditions with the USP23.
2.1.1 United States Pharmacopoeia in terms of precision the amount of color to take under test solution, 0.50ml, adding 0.50ml acetic anhydride, mixing. Then add 5.0ml glacial
acetic acid, put it aside for 5min, account for tons of hydrogen by adding 0.50ml mouth alcohol test solution, placed so that the color 30min.
2.1.2 improved conditions for precise amount of color to take under test solution 1.0ml, adding 0.10mol / L
hydrochloric acid 4.0ml, shake, plus alcohol test solution population accounted for tons of hydrogen 10.0ml, mixing, heating in boiling water for 5min, Yu Bing bath cooling, and then placed at room temperature for 15min.
I account for tons of hydrogen-alcohol test solution was
prepared to take 10% of the total tons of hydrogen mouth alcohol methanol 0.02ml, home 100ml Liang Ping, the ice 20ml acetic acid and hydrochloric acid 1ml, shake, using glacial acetic acid diluted to the scale.
2.1.3 Preparation of standard curve said precision reference standards appropriate to take to erythromycin, with pH6.8 phosphate buffer dissolved and diluted into
0.07,0.14,0.21,0.28,0.35,0.42,0.49 and 0.56mg/ml, respectively the standard solution. Precise amount of each check 1.0ml,
color according to the above method to measure absorbance at 540nm wavelength. A degree in order to absorb the standard solution concentration C (mg / ml) regression, have standard curve equation: A = 1.8452C-0.0042, r = 0.9998.
2.1.4 Solution stability test at room temperature to take the above 0.28mg/ml of the standard solution at room temperature placed, respectively 0,1,2,4,6 and 8h precise amount of color to take 1.0ml measured. The results showed that the absorption of solution in little change in intensity in 4h.
2.1.5 recovery test precision that take dirithromycin 11,14 and 17mg, respectively, 50ml Liangping home, by adding the amount of blank prescription accessories, with pH6.8 phosphate buffer dissolved and diluted to the scale, shake ,
filter. Precise amount of filtrate were added to take 1.0ml, according to the above method of color, were measured at 540nm wavelength absorption. Calculate the measured volume and the recovery rate, the results see Tab.1.
2.1.6 Determination of taking this product, first with hydrochloric acid solution (9 ? 1000) 900ml of solvent, using
basket method, rotation speed 100r/min, after 2h, per tablet enteric-coated films are not allowed to have cracks or softening phenomena; followed by phosphorus salt buffer (pH6.8) 900ml of solvent, 45min, when to take solution 10ml, filtration, taken for the test items as a renewal of the filtrate solution. Another precision that an appropriate reference substance taken to erythromycin, with pH6.8
phosphate buffer dissolved and diluted to 0.28mg/ml solution, as a reference substance solution; precision to take the above-mentioned solution, the volume of 1.0ml, adding 0.10mol / L hydrochloric acid 4.0ml, shake, together accounted for tons of hydrogen imported alcohol test solution 10.0ml, mixing, heating in boiling water for 5min, Yu Bing bath cooling, and then placed at room temperature for 15min. With a blank reagent solution as control, was measured at 540nm wavelength absorption in order to calculate the ratio between the release of percentage.
2.2 sulfuric acid method of color
Color terms used to erythromycin enteric-coated tablets
with the trial under the same condi