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Study on the Two Different Routes of Absorbing APIC in Rats and Enteric-coated APIC Solid Dispersion

Author: LiuMaoChang
Tutor: WangKaiPing
School: Huazhong University of Science and Technology
Course: Pharmacy
Keywords: Angelica polysaccharide iron complex Artificial gastric juice Artificial intestinal fluid Pharmacokinetics Atomic absorption spectrophotometry Enteric solid dispersion Force gadfly energy
CLC: R965
Type: Master's thesis
Year: 2010
Downloads: 27
Quote: 0
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Abstract

In this thesis, the pharmacokinetic of Angelica polysaccharide iron complex (APIC) bulk drugs exist two different absorption route, and the basis of APIC made enteric solid dispersion and its in vitro and in vivo performance inspected, and finally force which enjoys similar imported drugs the particle dosage form structure of the capsule contents can study to provide theoretical and experimental basis for the the APIC enteric formulation of design. The experiment mainly APIC in rats two different absorption route; enteric solid dispersion APIC Research; force which enjoys the the capsule content structure of particles available research part. First part of APIC in rats two different routes of absorption studies the APIC in vitro performance visits indicate that the release of iron ions in the environment of artificial gastric juice, no iron ion dissolution in distilled water and artificial intestinal fluid environment, still polysaccharide iron molecules form of APIC two different ways of administration to explore the form of free iron ion absorption in rats in vivo and directly to the form of polysaccharide iron complex molecules absorb two different absorption route. Normal rats were APIC high, medium, low dose without ascorbic acid ig ig plus ascorbic acid and duodenal administration experiment to correspond visits APIC without ascorbic acid orally both The form of iron ions have absorption in molecular form, the APICs added ascorbic acid orally completely absorbed in the form of iron ions and direct duodenal administration APIC only in molecular form absorbed pharmacokinetic process. Atomic absorption spectrophotometric method for the determination of serum iron concentration at each time point, calculating pharmacokinetic parameters DAS2.0 software. The results show that the APIC pharmacokinetics in rats are in line with the two-compartment model, and also increase accordingly AUC increasing dose in the dose range used in this experiment. Equal doses administered orally, without AUC than the addition of ascorbic acid, ascorbic acid group is slightly larger group AUC. And confirmed APIC polysaccharide iron complex molecular forms duodenal absorption. To arrive, APIC both the form of free iron ions can polysaccharide iron complex molecules form of duodenal absorption. Second part APIC enteric solid dispersion APIC preliminary studies show that the artificial intestinal fluid in vitro environment can exist in the form of polysaccharide iron molecules, and can duodenal absorption play blood iron role polysaccharide iron molecules form, this form iron absorption can avoid the adverse reaction of free iron ions gastrointestinal irritation. This article APIC prepared enteric solid dispersion and visit their in vitro and in vivo performance and APIC absorbed most of the form of a polysaccharide iron molecules in the preparation of the enteric feasibility. Eudragit L100 as enteric carrier prepared by freeze-drying APIC enteric solid dispersion by infrared spectroscopy to evaluate the quality of the APIC solid dispersion. Examine the characteristics of its dissolution in artificial gastric juice and artificial intestinal fluid and to force the gadfly for the reference formulation pharmacokinetic comparison study of rats. Experimental results show that: the infrared spectrum shows a significant difference in the absorption peak of the simple physical mixture of the enteric solid dispersion APIC APIC bulk drugs and excipients, solid dispersion APIC with excipients intermolecular bond to form intermolecular hydrogen bond, APIC in enteric accessories was highly dispersed state. The in vitro dissolution experiments show that the APIC enteric solid dispersion the 3h dissolution in artificial gastric juice is only 27% and more than 94% of the drug dissolution in artificial intestinal fluid 3h, reaching a sustained release in the stomach and slow the absorption site duodenum rapid release effect. The pharmacokinetic results show APIC enteric solid dispersion with force gadfly after administration rats serum iron concentrations were significantly increased, and the two drugs in this experiment, the selected dose range AUC increases with dose increases. The same dose of solid dispersion group the AUC than force the gadfly group AUC small, gossip can be compared with the formulations ripe listed drug force, enteric solid dispersion prepared in this laboratory have improved space. The experiment results also confirmed the APIC enteric solid dispersion the physical APIC substantially in molecular form to be absorbed in the duodenum and blood iron role, APIC made enteric solid dispersion is feasible. The third part of the force which enjoys a capsule dosage forms of content particles Structure of imports preparations force gadfly mainly a polysaccharide iron complex drug enteric particles iron supplement. It does not generate free iron ions in the gastrointestinal tract, but in the form of a polysaccharide iron molecules in the duodenum is absorbed. This experiment by force gadfly Capsules the content particle formulations structural study to provide a theoretical and experimental basis for the the APIC enteric formulation of design. To study the in vitro dissolution experiments in different solvents Form of gossip can the overall nature of the particles. The force which enjoys a white substance can brown crust and the center of the particle separation and inspect its properties. The experimental results show that the force which enjoys particles is a release in the stomach, the intestines immediate release, controlled release formulations. Determination of iron content and IR spectra analysis showed that the force gossip can brown-black shell particles polysaccharide iron complex. By the AFM map speculated force gossip can black shell enteric small round particles adhesions formed. Force the gadfly energy center white substance does not contain iron, sugar content of 79.14%, is presumed to be a biological polysaccharide, played with a mixture of some excipients formulations support and promote the role of particle disintegration. Therefore believe that force which enjoys a capsule content particles in some kind of a mixture of polysaccharides and accessories for the grain core, coated enteric polysaccharide iron complex iron new formulation. Force gadfly main drug is dextran and ferric synthesized polysaccharide iron complex, APIC has a similar molecular weight, molecular structure and physical and chemical properties, so the same APIC made enteric solid dispersion wrapped the formation of spherical granules and at excipients tablets core outer loaded capsule, thereby obtaining the APIC enteric pharmaceutical formulations.

Study on the Two Different Routes of Absorbing APIC in Rats and Enteric-coated APIC Solid Dispersion

Abstract

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