Design And Evaluation Of Vinpocetine Inclusion Complexes And Sustained-release Hydrophilic Polymer Matrix Systems

In the present study, the in vivo rat intestinal absorption characteristic of vinpocetine (VIN) was firstly studied by single-pass perfusion technique. The comprehensive studies on VIN and VIN-inclusion controlled release matrix systems were performed based on the comparison of polymer characteristics including polyethylene oxide (PEO) with respect to their behavior in drug delivery. Five main sections were included in this paper:1,The study on the mechanisms and kinetics of drug absorption by rat single-pass intestinal perfusion technique:The results showed that VIN could be well absorbed at all segments of intestine in rats where there was no special absorption site, which suggested that VIN could be defined as Class II drug in accordance with BCS (Biopharmaceuticals Classification Scheme) and was a good candidate for a sustained-release system. Increasing perfusion flow rate produced increased values of Ka and Papp, which indicated food might effect drug absorption process. Drug concentration ranged from 1 to 50 ug/ml and HP-P-CD concentration ranged from 1 to 4%(w/v) had no significantly effect on the values of Ka and Papp, which indicated the mechanism of the intestinal absorption of vinpocetine was transferred to cell via passive diffusion, and inclusion with CD would have no inhibition effect on drug absorption.2, The comparison of characteristics of three matrix polymers including PEO :(1) The type and molecular weight of polymer had significant effect on erosion rate, the sequence of which was SAL(L)>>SAL(H)>>PEO80>PEO200>PEO300>PEO400 =K4M >K15M ~ PEO600> KIOOM. A theoretical mathematical model was developed for describing the relationship between PEO erosion rate and PEO weight average molecular weight: Jp M-1241, where the exponent of-1.241 was very close to the exponent of-1.1304 obtained from practical determination and which firstly provided a more comprehensive description to the polymer erosion law involved in drug release process from hydrophilic matrix tablet based on the polymer molecular micromechanism lever.(2) The gel layer strength of pure PEO, HPMC and SAL matrixes in water was compared by investigating the diffusion coefficients of model drug (theopylline) from gels at Cp,dis, the sequence of which was PEO HPMC>> SAL(H) >>SAL (L).The molecular weight of PEO and HPMC had no significant effect on gel strength, while the molecular weight of SALshowed significant effect on gel strength, and moreover, the pH and ion strength of medium had also showed pronounced effect on physical properties of SAL polymer.(3) Image analysis software "Color contractor" was demonstrated a valid tool to investigate the structure of gel layer surrounding the polymer matrices. The movement rate of the three fonts existed in swelling matrices measured by this method showed a notable difference between pure HPMC and PEO matrices. The gel layer thickness of all types of HPMC matrices was only slight different for three Methocel grade matrices and increased constantly, whileas the molecular weight of PEO had notable effect on gel layer thickness. Especially, to the lower molecular weigh PEO matrices, the gel layer thickness increased quickly early on and then slowed down sharply due to their higher erosion rates.3, The design of VIN controlled-release systems:(1)With HPMC as hydrophilic matrix material, the type and content of HPMC and the amount of citric acid (CA) were two most important factors influencing drug release rate; water soluble additive (lactose) improved drug release rate while water insoluble additive (starch) and particle size of HPMC had little influence on the drug release rate. The compression force had no significant effect on drug release rate, whereas preparation method, the diameter of tablets, rotate speed and pH value of medium had all influences on the drug release rate.(2) With PEO as hydrophilic matrix material, the content and molecular weight of PEO ,the amount of C A and pH value of dissolution media all had influences on the drug release rate while pre...