Studies On The Mechanism Of The Absorption Of Cardiovascular Pharmaceuticals In Microporous Starch And The Preparation Technology Of Sustained Release Drug For Captopril

The raw material of this study is corn starch. Then the corn starch was made into microporous cross-linking and esterifled microporous starch of good condition through amylorrhexis, cross linking reaction and esterification. The absorption of the cardiovascular pharmaceuticals such as Captopril and Lovastatin in the starch and its mechanism have been studied. Meanwhile ,the release property of the dosage in imitated intestine systems was studied. The starch and the Captopril were encapsulated and compressed into release-sustained dosage on the basis of release property. Then the content of Captopril was determined by HPLC. Quality and stability of the tablets were evaluated further. The results of this thesis are as follows.(1) A series of parameters of the raw starch, cross-linked starch, microporous starch, microporous cross-linked starch and esterified microporous starch were determined through experiments. The rate of water absorption and oil absorption in microporous starch, cross-linked microporous starch and microporous esterified starch significantly increased. The rates of water absorption in microporous cross-linked starch and esterified microporous starch were 98.12% and 96.34% respectively, while the rates of oil absorption were 1.5 mL/g and 1.6mL/g.(2) Two optimal starches have been determined in terms of absorption. Among the five starches the microporous cross-linked starch is the most potent for absorbing the hydrophilic substance like Captopril at 0.575g/g while the esterified microporous starch is for the oleophilic Lovastatin at 45.8mg/g. This phenomenon indicated that microporous starch is prone to absorb hydrophilic pharmaceuticals.(3) The optimal absorbing conditions for hydrophilic Captopril in microporous cross-linkedstarch have been determined through experiments. The conditions are, using 40uL cross-linking agent per 100 g starch, pH 4, dose at 2.5g, absorbing time for 1.5 h, absorbing temperature at 20℃, the initial concentration of the Captopril at 50mg/mL, the concentration of sodium chloride solution at 0.1 mol/L. The absorbing was divided into several batches and the solution was not stirred. With these optimal conditions, the absorbing volume can amount up to 0.746g/g.(4) The absorption mechanism for hydrophilic Captopril in microporous cross-linked starch was determined. As a physical process, the absorbing was equilibrated in a short time. The whole process can be divided into three steps: (1) Captopril migrates from water solution into the liquid limiting membrane of cross-linked microporous starch; (2) Captopril diffuses from the liquid limiting membrane of cross-linked microporous starch to the inner part of cross-linked microporous starch; (3) At the inner part of cross-linked microporous starch, Captopril bonds to the absorbing site. The former two steps determines the rate of absorption. The absorbing process is exothermic, indicating that lower temperature is conducive to the absorbing volume. The absorption isotherm is congruous with the Langmuir absorption isotherm. The Langmuir parameters are 0.9314, 0.9616, 0.9742 for Qm and 0.0756, 0.0495, 0.0341 for b. The equation of reaction rate for Captopril absorption is dQ₁/dt=0.604Q₁, dQ₂/dt=0.484Q₂/t. dQ₃/dt=0.682Q₃/t.(5) The stableness, precision and recovery rate of the measurement method for the degree of release from tablets were assayed in experimentation. The method was also used to determine the optimal conditions for release. Except the gelatinized starch, all other three kinds of Captopril tablets made from adhesives were able to release sustainingly, with the EC being the best and release time being long up to 10h. EC functions as an adhesive and on.the other hand, has the function of sustained release synergically with microporous starch. The conditions of concentration at 3%, dosage of 5% potentiated the effects of EC to the most and the rate of release was independent from pressure. The medium has the significant influence on the release of Captopril. Captopril could not release its content completely in the water, with cumulative release percentage of only 46.2% and in imitated stomach juice 1 and stomach juice 2 with cumulative release percentages of 76.2% and 77.2% respectively. The microporous starch was not digested completely. The cumulative release percentages in imitated intestine juice 1, 2 and 3 were 78.9%, 80.4% and 89.9% respectively. The outcome was the best when Captopril was released firstly in imitated stomach juice 2 and latterly in imitated intestine juice 3, with the cumulative release percentage of up to 91.2%. It released most slowly when lactose was the additive into the tablets, starch modestly, and calcium sulphate most rapidly.(6) The optimal process variables for tablet production were founded. These variables are ethylcellulose concentration at 3%, dose 5%, granule aperture 40 meshes. The three batches of...