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Studies on the Enhancing Effects of Dimenthyl-β-cyclodextrin and Chitosan on Oral Bioavailability of BMCP25

Author: ChenShuiJuan
Tutor: GaoFeng
School: East China University of Science and Technology
Course: Pharmacy
Keywords: Insoluble drugs Dimethyl-β cyclodextrin Chitosan Oral bioavailability BMCP25
CLC: R96
Type: Master's thesis
Year: 2012
Downloads: 63
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Abstract

. BMCP25 is a new synthesis of the benzimidazole derivatives and pharmacological experiments show that having good in vitro anti-hepatitis B virus (HBV) activity, can effectively inhibit the secretion of antigen and HBV DNA replication. This topic use of dimethyl-β-cyclodextrin (DM-β-CD) and chitosan, improving the insoluble drug BMCP25 oral bioavailability in rats and rabbits, and its mechanism through intestinal permeation experiments discussed . High performance liquid chromatography (HPLC) of the BMCP25 vitro detection methods. Determination BMCP25 water solubility, and predict the the Pow observed before the study of the physical and chemical properties of its surface polymorph study drug prescription. Screening cyclodextrin inclusion complexes and different feeding molar ratio was prepared by BMCP25/DM-β-CD complex and characterized, BMCP25/DM-β-CD complexes can significantly increase water solubility BMCP25 and improve the dissolution rate. Using the same amount of sliding scale, enteric-coated capsules filled the BMCP25/DM-β-CD solid powder and chitosan. Packing variation, disintegration time and quality assessment are in line with the 2010 version of the pharmacopoeia. Establish a sensitive, accurate, and easy BMCP25 rats and rabbits HPLC analysis method for pharmacokinetic studies in rats and rabbits. ODS column (250 × 4.6 mm, 5μm); mobile phase: acetonitrile - water - formic acid volume ratio (96/4/0.002); flow rate: 1.0 mL / min; column temperature at room temperature using the column: Platisil (?); detection wavelength of 216 nm; injection volume 20 μL samples; drug retention time of 5.9 ~~ 6.1 min, limit of quantification was 0.05μg/mL. BMCP25 in rat plasma concentration 0.08-10μg/mL range good linearity (R2 = 0.9999); showed good linearity (R2 = 0.9992) in the range of the rabbit plasma concentrations of 0.05 ~ 10μg/mL. BMCP25 in rat plasma recoveries in the range of 91.2 to 104.1%; rabbit plasma recoveries between 96.2 and 105.0%. In rat plasma days day precision were lower than 9.1% and 9.8%, respectively; intraday and interday precision measured in rabbit plasma were lower than 9.1%, and the stability of each sample. After BMCP25 original drug oral gavage, the rats unable to detect the concentration of the blood. Rat oral administration BMCP25/DM-β-CD composite absolute bioavailability (16.84 ± 5.88)%, enteric capsules in rabbits administered orally the absolute bioavailability (46.52 ± 9.62)%. The Fluorescence prime (FL), rhodamine (R123) as markers Ussing Chamber rat jejunal mucosa permeation experiments, study of DM-β-CD and chitosan alone or in combination of absorption in the small intestine of markers . 0.5% chitosan alone acting on the FL, intestinal permeation to obtain the apparent permeability coefficient (Papp) of the enhanced permeability ratio was 4.33; 10 mM DM-beta-CD and 0.5% chitosan binding FL, Papp, penetration-enhancing ratio 8.89. 10 mM DM-β-CD alone R123, outer discharge rate of 3.62 is reduced to 1.43; 10 mM DM-beta-CD and 0.5% chitosan binding of R123, outer discharge rate of 3.62 Less small to 1.19. The two accelerators jointly acting on the the the cell bypass transporter drug or the P-gp substrate, can significantly increase the drug absorption in the intestinal mucosa (P lt; 0.05), helps to increase its oral bioavailability.

Studies on the Enhancing Effects of Dimenthyl-β-cyclodextrin and Chitosan on Oral Bioavailability of BMCP25

Abstract

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