The Preparation Of Alginate Enteric-coated Hard Capsules

Alginate is a kind of polysaccharides which are extracted from the seaweed, composed of 1,4-poly-P-D-mannuronicacid and a-L-guluronic acid. Generally, alginate exists in the form of sodium alginate. Sodium alginate is a water-soluble alginate which has good film forming properties. When hydrated alginate is affected of calcium ions, it will greatly increase the viscosity of the solution to improve film reforming performance, which is suitable for the preparation of enteric capsules.Enteric capsules can be divided into two classes:enteric soft capsules and enteric hard capsules. At present, enteric soft capsules are almost made of alginate, and which is very mature. On the other side, the products of enteric hard capsules are mostly enteric coated gelatin hard capsules, but this traditional enteric coating method neither impacts drug quality or capsule stability because of special character of gelatin. Using alginate to produce enteric-coated hard capsules will not only develop a new method of preparation enteric-coated hard capsules, but also develop some new foodstuff to satisfy Muslim people s need.This thesis focused on using cross linking of alginate and cationic to produce enteric hard capsules, based on the preparation of gelatin capsules, Theological behavior and film forming properties of alginate. The main content of this research was as follows:1. The preparation of gelatin hard capsules.The wall-forming was use to confirm the processing condition of sol-melting and drying. The results showed the optimum processing condition was that the concentration of gelatin and CMC was 30% and 0.2% respectively, sol was melted under 65℃for 70min, and then dried under 40℃for 60min. The capsules'loss on drying was 14.2±1.3% and ignition residue was 1.2±0.33%, disintegration time was 2.51±0.12min in water and 2.14±0.2min in acid solution, which met the requirements of China Pharmacopeia and national standard. 2. Rheological properties and film reforming properties of LV (low viscosity) alginate were investigated.The results showed that LV alginate was pseudoplastic fluid and tits flow curve had a good correlation with the power law model. Rheological properties of alginate were affected by its concentration and temperature. Apparent viscosity exhibited shear thinning behavior following the power law model. Apparent viscosity increased with the increase of concentration, and decreased with the increase of temperature. The decrease in viscosity followed an Arrhenius temperature dependence. Alginate solutions didn't exhibit typical "weak gel" properties by small strain oscillatory measurements.The rigidity of LV alginate films was good and the flexibility was weak. The tensile strength was no less than 28MPa and elongation at break was 10-37%. As a result of the dense composition, LV alginate films had good gas permeation, water resistance and oil-resisting. The water vapor permeability was 0.16g·mm/m2·h kPa, drop penetrationtime was longer than 800min, air transmission coefficient was below 7.2cm3·cm/cm2·s·kPa and oil-resisting was under 0.02g·mm/m2·d. The LV alginate films had good film reforming property, the transmittancy of film being about 85%.3. The preparation of alginate enteric-coated hard capsulesReferring to the preparation of gelatin hard capsules, alginate enteric-coated hard capsules'process flow was confirmed as gel-melting, shell-making, calcification, drying. The wall-forming was use to confirm the processing condition. The results showed the optimum processing condition was as follows, the concentration of alginate and glycerol was 12% and 3% respectively, and 2% CaCl2 was used for calcification for 15 s, and the water content of alginate enteric-coated capsules was 15% after drying. The disintegration time and combustion remains was 43±1mins and 26.4±0.99%, while the appearance quality met the requirement of China Pharmacopeia and national standard too.