An Investigation Of Eudragit For Preparing Enteric Hard Shell Capsules

Enteric capsules can release drug in intestinal tract, so gastric-juice-sensitive drugs or stomach-irrtated drugs would have wider application by means of enteric capsules. The products of Enteric capsules are mostly enteric coated gelatin hard capsules, but this traditionary enteric coating method either impacts drug quality or capsule stability because of special character of gelatin.In this research, acetaminophen was chosen as the model drug. Eudragit films were firstly characterized and Eudragit was chosen as the capsule shell material, while ethanol as the solvent, glycerin as the moistening agent, triethyl citrate(TEC) as the plasticizer, titanium oxide as the coloring agents, magnesium stearate as the assistive capsule material, methyl paraben and ethyl paraben as the antiseptic. The dosage of different excipients was optimized. Eudragit enteral capsules were finally prepared and pharmaceutical evaluation was taken too.Different types of eudragit films were prepared, their properties, such as microstructure, film ductility, film permeability, film dissolvability in different pH solvent, and the glass transition temperature(Tg) were studied. Materials for preparation of eudragit capsules were optimized through characterizing the film structure. Plasticizer had great influence to film microstructure and glass transition temperature, the addition of plasticizer could make the film more smoothing, thus film tenacity and intensity were strengthened. Different kinds of plasticizer were chosen to add to the films and DSC was taken, it proved that Tg had most decreased when triethyl citrate was added.Research to firm ductility and firm permeability showed great change in tensile strength and break extensibility from dry films to wet films. Eudragit(?)L100-55 could absorb water more easily than Eudragit(?)S100, and the increase of capsule moisturecould also increase capsule friability, the addition of glycerin could eliminate the influence.Different film solubility in different pH solution could be achieved through adjusting the ratio of Eudragit?S100 to L100-55 in films. Drugs could be encapsulated in eudragit films, and the content of eudragit could also be adjusted, thus drug release in different pH solution could also be expected.Titanium oxide, magnesium stearate and glycerin were chosen as the excipients in capsule preparation. Viscosities of eudragit solution, capsule formability, capsule appearance, and capsule moisture were chosen to evaluate effects of different excipients on capsule preparation. Titanium oxide and magnesium stearate could increase the solution viscosity and make the capsule appearance better. As the moistening agent, glycerine made the capsule moisture keep in a good state. Optimized formulation was achieved after comparing influence of different excipients to capsule preparation.Analytical method of acetaminophen was established, as the model drug, acetaminophen was used to evaluate the influence of rotation speed, excipients, and storage condition to release property of EL-55 capsules. Release profiles showed that rotation speed had almost no effect to the release behavior, and the addition of delayed release excipients (ethyl cellulose) could make drug release slowly, but the effect was not obvious. Accelerative stability test indicated EL-55 capsules should be kept in airtight condition.To prepare colon specific drug release capsules, the possibility of ES as the capsule shell material was also been investigated. Titanium oxide, magnesium stearate and glycerin were chosen as the excipients, formulation and prepare technology were optimized and well-performance ES capsules were prepared.Acetaminophen was chosen as the model drug, drug release test of ES capsules was taken to fulfill the requirement of Chinese Pharmacopeia to colon target enteric capsules, and acetaminophen was also chosen as the model drug. It showed almost nodrug released in pH 6.8 phosphate buffer(PBS)(accumulation release was less than 5%), however, accumulation release achieved more than 95% after 2h in pH 7.2 PBS, met the requirement of colon target drug delivery. Accelerative stability test showed ES capsules had good stability in high moisture and temperature, and release profiles had no significant change after three months accelerative test.ES and EL-55 were then mixed at the ratio of 1:1,2:3,1:4,1:5:1:6:1:7:1:8,1:9 to prepare capsules. The mixture was solved in ethanol, and excipients were added in the solution, viscosity of the solutions was carefully controlled, and the capsules were prepared by a dipping-process. Same model drug was used to investigate in vitro release. The result showed that with the increased content of ES in capsules, the release rate of capsules slowed down.