Synthesis Of Starch Acetate And It’s Application In Preparation Of Sustained Release Tablets Of Proanthocyanidin

Starch is a kind of source-rich,low-priced and reproducible natural macromolecule, However, it contains a large number of hydroxyl groups within the molecule that are hydrophilic which made its application limited.Therefore,starches are always treated by physical,chemical or enzymic modification to obtain special properties.Proanthocyanidin is a kind of polyphenol compound which is widely existed in the nature,it possess a wide range of biological activities such as antioxidation,anti-aging,radioresistance,antiatheroscloresis, antifatigue,memory ascending and so on.Nevertheless,few products origined from proanthoc yanidin could be found in markets, especially for sustained-release preparations.This thesis mainly investigates starch acetylation under water bath and microwave assista-ce and the effect of reaction conditions on dgree of substitution.FT-IR,SEM,XRD,LPSD and DSC,GPC,Low-field NMR and other modern analytical technologies are all employed to analysis the change of structure and physicochemical properties of starch after modification.Especially,this thesis investigated the impact of reaction conditions on structure and physicochemical properties of starch.Using starch acetates as excipient, proanthocyanidin as main drug to produce sustained-release tablets.Build up the method and standard to determine in vitro release degrees and also investigated the mechanism of drug release from the sustained-release tablets.The results of this research are follows:1. Optimal condition for synthesis of starch acetate from corn starch was investigated through response surface method, it is based on single factor experiments which study the effect of catalyst amount, acetic acid to acetic anhydride volume ratio, reaction time and reaction temperature on degree of substitution.Through analysis of regression equation and response surface, the optimum technology for synthesis was obtained as follows:catalyst amount 0.11 mL, acetic acid to acetic anhydride volume ratio 1:1.39, reaction time 1.59 h, reaction temperature 87.61℃. By verification experiment, the maximum DS of starch acetate is 2.95. 2. FTIR results show that the hydroxyl hydrogens in each glucose unit of starch acetate have been gradually replaced by acetylgroups, when the determined DS increased, the content of acetyl groups also increasesd. As it is shown from SEM, the surface of starch acetate became much rougher, the porosity increased and formed cellular structure, which indicating the esterification occurred not only on the surface but also inside of starch structure. Both Tg and Tm decreased which implies good thermoplasticity of starch acetates reflected by DSC results.As shown from x-ray results,the origin cystal structure was totally destroyed,two new dispersion peak has been shown in the image at 8.9°and 19.8°,together with the decrease of crystallinty.3. Under microwave assistance, volumn ratio between acetic acid and acetic anhydride and catalyst amount has a significant effect on DS.DS first rised and then decreased with the change of both volumn ratio between acetic acid and acetic anhydride and catalyst amount.Under the ratio of 1:1,catalyst amount of 0.19 mL,the highest DS of 2.92 was obtained.Acetic acid possess more strong penetrability than acetic anhydride, so it can cause more destruction to the double helix of starch molecular.Therefore,when the ratio of acetic acid is higher,the surface of starch granule is more rough,the size of average diameter is smaller,Tg and Tm decreased still more,the average molecular weight is also lower. Sulfuric acid has two side of effects as catalyst.First,it can enhance reactivity of acetylation which lead to rise of DS.Another its high acid and strong oxidizing property make the starch acetates splited more easily.It also caused the decrease of crystallinity,break of molecular and significant decrease of molecular weight.4. Proanthocyanidin is a kind of drug which has moderate half-life period,good dissob ility and wide security window,which is quite suitable to be used for sustained release.After stability experiment and wavelength specificity experiment,also take into consideration of physical truth,.the method to determine in vitro release degrees are as follows:rotating basket method with the rotating speed of 100±1 r/min.Choosing simulated gastric fluid as dissolution medium,volumn is 900 mL Sampling 5 mL at 0.5h、1h and every 1 h after that until the tablet distintegrated or it reaches release end,determine the content of proanthocyanidins using direct colorimetric method at 280 nm.The standard is fixed as follows:Drug release under 20% at 2h, under 50% at 5h and over 90% at 10 h.5. Adopt direct presser method,using proanthocyanidins as main drug.Compare the release qualities of starch acetates with CMC,HPC and NS.The release differences of SA with different DS and synthetized under different conditions were both contrasted. SA sythetized under water bath with DS of 2.92 exhibited best sustained release qualities.Drug release 29.11% at 2 h,48.61% at 4 h and finally 95.20% at 10 h.The prescription of tablets is as follow:LSPC--25%;βcricoid dextri—5%; magnesium stearate—69%;tablet weight 100±1mg,hardness—7.0 Kg/cm2 or so.6. With the assistance of SEM and Low field NMR imaging,release of proanthocya-nidins from sustained-release tablets was studied.lt turns out that this sustained-release tablet prepared is a Matrix type.Drug release from the tablets according to HiguchiF equation.Drug release mainly from tiny pores in the matrix,the matrix shows no change during the release process.There are more pores and crevice in the tablets made of SA with low DS than high DS,which explains for the faster drug release phenomenon of tablets using low DS SA as excipients.