Study On The Two Different Routes Of Absorbing APIC In Rats And Enteric-coated APIC Solid Dispersion

This paper summarizes the pharmacokinetics of the crude drug of Angelica sinensis polysaccharide-iron complex (APIC) on account of the two different routes of absroption, preparation of the enteric-coated APIC solid dispersion based on the above to investigate the properties in vivo and in vitro of it and the study on dosage form and structure of the granules in Niferex capsule to provide academic and experimental base for enteric-coated APIC formulation. The main contents of the paper were consisted of three parts: the study of two different routes of absorbing APIC in rats; study on the enteric-coated APIC solid dispersion; the study on dosage form and structure of the granules in Niferex capsule.PartⅠthe study of two different routes of absorbing APIC in ratsFrom the study on the property in vivo and in vitro of APIC we know that ferric ion can be released from APIC in artificial gastric juice, but no ferric ion can be released in distilled water or in artificial intestinal juice which means that APIC mainly exists as polysaccharide-iron molecular pattern. So we investigate the two different pathway of APIC absorbed in the form of ferri ion or directly in the form of polysaccharide-iron molecule in normal rats with different administration. Normal rats were assigned into three groups, APIC low, medium, and high dosage groups, ig administration with no ascorbic acid added, ig administration with ascorbic acid added and id administration were performed to investigate the pharmacokinetics of APIC absorbed in the form of ferric ion, in the form of ferric ion and polysaccharide-iron molecule and only in the form of polysaccharide-iron molecule correspondingly. Serum iron concentration was assayed by atomic absorption spectrometry after ig administration and id administration of APIC respectively. The pharmacokinetics parameters were analyzed by DAS2.0 program. The concentration-time curves of APIC in rats were fitted to two-compartment model and the AUC increased accordingly as the accrescence of the dosage in the dosage range chose in this experiment. The AUC of the group with no ascorbic acid added is larger than that of the group with ascorbic acid added of the same APIC dosage after ig administratiom. And APIC can be absorbed in the form of polysaccharide-iron molecule at duodenum. Thus draws the conclusion: APIC can be absorbed not only in the form of ferri ion but also in the form of polysaccharide-iron molecule at duodenum.PartⅡStudy on the enteric-coated APIC solid dispersionThe preliminary study suggests that APIC mainly exists as polysaccharide-iron molecular pattern in artificial intestinal juice and can be absorbed in the form of polysaccharide-iron molecule at duodenum to enrich the blood and iron. This kind of absorption of iron can avoid the side effect of gastrointestinal irritation caused by ferric ion. So we prepared enteric-coated APIC solid dispersion and investigated its properties in vivo and in vitro and the feasibility of APIC absorbed mainly in the form of polysaccharide-iron molecule in enteric-coated preparation. Eurdgit L100 was regarded as carriers. APIC solid dispersion was prepared by freeze drying method. IR technology was used to evaluate the quality of APIC. We determined the dissolution rate of APIC in artificial gastric juice and artificial intestinal juice respectively and study its pharmacokinetics in rats with Niferex as reference. The results showed there was significant difference in the IR diagram between the APIC solid dispersion and the simple mixture of APIC and adjuvant. The APIC forms intermolecular hydrogen bond with the adjuvant which indicats the APIC exists mainly within the molecular state in solid dispersion. The results of the dissolution test in vitro showed that the dissolution rate of enteric-coated APIC solid dispersion was only 27% in artificial gastric juice within 3h, and 94% in artificial intestinal juice within 3h. That means enteric-coated APIC solid dispersion has a good dissolution rate in artificial intestinal juice and sustained released in artificial gastric juice. The pharmacokinetic study showed that the both serum iron concentration in rats rose obviously after the administration of enteric-coated APIC solid dispersion and Niferex and the AUC of both drugs increased accordingly as the accrescence of the dosage in the dosage range chose in this experiment. The AUC of enteric-coated APIC solid dispersion was lower than that of Niferex with the same dosage. It means compared with the listed drug Niferex with mature dosage form, there is still roon for improvement on enteric-coated APIC solid dispersion which we prepared. The experimental results also validated that enteric-coated APIC solid dispersion can make sure that APIC is absorbed mainly in the form of polysaccharide-iron molecule at duodenum to enrich the blood and iron and we can say that the thought of preparing enteric-coated APIC solid dispersion is advisable.PartⅢThe study on dosage form and structure of the granules in Niferex capsuleImported Niferex is a kind of iron supplement made up of many enteric-coated granules, the primary drug of which is polysaccharide-iron. Niferex does not dissociate iron ion in gastrointestinal tract and it is absorbed in the form of polysaccharide-iron molecule at duodenum. This experiment looks into the dosage form and structure of granules in Niferex capsule in order to provide academic and experimental base for enteric-coated APIC formulation. We took the dissolution test in vitro and studied the morphology of Niferex in different menstruum to investigate its global property. Then we separated Niferex into brownish black shell and a white substance in center and study the properties of both. The results showed Niferex has a controlled-release dosage form which has a good dissolution rate in artificial intestinal juice and sustained released in artificial gastric juice. From the determination of iron content and IR diagram we know that the content of brownish black shell is polysaccharide-iron. Judging from the AFM diagram we speculate that the black shell is made up of many round enteric-coated drug particles. There is no iron in the white substance in center of Niferex and the sugar content of it is about 79.14%, from which we suppose that the white substance is a mixture of some kind of polysaccharide and adjuvant to provide a function of supporting the dosage form and promoting disintegration. So we can consider that the granules in Niferex capsule belong to a new dosage form for iron supplement which consist of some kind of polysaccharide and adjuvant core encased in enteric-coated polysaccharide-iron. The primary drug of Niferex is a kind of polysaccharide-iron which is synthesized with dextran and high valence ferro ion. This kind of polysaccharide-iron has the similar molecular weight, molecular structure and physics and chemistry property with APIC. So we can also make the adjuvant core encased in enteric-coated APIC solid dispersion to form spherical granules and prepare capsules to get the APIC enteric-coated pharmaceutical preparation.