| According to statistics of the World Health Organization, about30million people worldwide suffered from varying degrees of anemia. Anemia is frequent in pregnancy and is often associated with adverse effects both in the mother and in the fetus. The mother may be plagued by easy fatigability, weakness and dyspnea, whereas the fetus may encounter an increased risk of preterm birth and mortality. Currently, anemia has become a global nutritional disease. The ferrous fumarate and folic acid capsules were a new kind of anti-anemia drugs. The ratio of iron and folic acid (150:1) was the newest proportion recommended by WHO. There were not any reports about ferrous fumarate and folic acid capsules at home and abroad.The first part. The preformulation study of ferrous fumarate and folic acid capsule. Ferrous fumarate and folic acid are added gradually with equal quantity and well mixed to obtain a powder mixture. Then the capsule was made. The formulation had rapid dissolution of utility component, simple of manufacture technique, and stable in quality and so on.The second part. Quality Standards. Chromatographic analysis was performed by using a Elite HPLC system (Elite Analytical Instruments Co. Ltd, Dalian, China),which consisted of P200pump,6-way valve sampler(GJ605), chromatogram workstation(WDL-85), and UV200detector. A Shim-pack VP-ODS C18(250×4.6mm,5μm) column was used. The mobile phase consisted of methanol and phosphate buffer (20:80, v/v), the pH was adjusted to6.3. The flow rate was1.0ml/min and the injection volume was20μl. The column temperature was maintained at30℃and the detection wavelength was fixed at282nm. Besides, the mobile phase was degassed and filtered through0.22um membrane filter before used. Folic acid can be well separated with impurities under this condition, and the resolution factor between the peaks met the requirements. The content of folic acid and ferrous fumarate were99.27%and99.30%, respectively; the folic acid’s related substance was less thanl%, while ferric salt was less than5%. It was also found that the cumulative dissolution rate of folic acid and ferrous both reached more than80%in15minutes.The third part. The stability study of the ferrous fumarate and folic acid capsules.The strong illumination test, accelerated test and long term test were researched. The results showed that the capsules were easily deliquesced in the condition of high humidity. They should be stored in a dry condition, the capsules were stable in the condition of accelerated test and long term test conditions. The fourth part. Acute toxicity.Firstly, we got the dose lethal range of0%and100%through the pre-experiment,which was872mg/kg and3672mg/kg. According to improved Karber’s method, LD50and95%reliable limit were counted. LD50was2199mg/kg and95%reliable limit was1948-2484mg/kg. LD50was732times higher than of clinical dose, which proved that the toxicity of the capsules was very small.The fifth part. General pharmacology. We chose1/20,1/10,1/5of LD50as a low, medium and high dose to investigate the influence of the drug on the central nervous system, cardiovascular system and respiratory system. The results were as follows:the low, medium and high doses of the capsules had no significant influence on locomotor activity and coordination(P>0.05), no significant synergy with subthreshold dose of Pentobarbital(P>0.05), no significant influence on blood pressure, heart rate and respiratory rate (P>0.05).The sixth part. Pharmacokinetics and bioavailability. After administration of the capsules and conventional tablets, we determined the rabbits’iron concentration at different time after administration of the capsules and conventional tablets by using self-built atomic absorption spectrophotometry method. We discovered the pharmacokinetic characteristics of the capsules in rabbits and compared the relative bioavailability between these two kinds of preparations. The results indicates that Cmax of the two preparations were (10.063±0.507) μg/ml、(8.845±0.486) μg/ml, the peak time of the two preparations were1.5h and (1.917±0.204) h, respectively. The peak time of the capsules was significantly earlier than the common tablets (P<0.05), while the peak concentration is also higher (P<0.05). The results of nonparameter test suggested that the capsules showed bioequivalence to the common tablets. |
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