The Preparation Of Algin Enteric Hard Capsule Shell In Calcium Ion Cross-linking System

With the continuous development of the pharmaceutical industry, the need of enteric capsule shell is increasing. The plant enteric hard capsule shell, not only can solve the defects of material of gelatin capsule shell, like the properties and raw material security, but also show the characteristics of high bioavailability, low dosage, protection against the stomach enzymes or acid and so on. Using algin to produce enteric hard capsule shell will not only open up a. new way to use brown algae resources, but also develop a new method of preparation enteric hard capsule shell with independent intellectual property rights.This paper focused on using cross linking of algin and Ca2+to manufacture enteric hard capsule shell, measuring the release characteristics and testing its performances based on the water vapor permeability of algin films. The main contents of this paper are as follows:1. The water vapor permeability of algin films was studied. The WVP of algin films was selected as an evaluation index and single-factor tests were determined the best conditions:glycerin concentration, algin concentration, sodium carboxymethyl cellulose (CMC) concentration, CaCl2solution cross-linking time and CaCl2concentration were, respectively,5%,8%,0.1%,12min and2%. Considering all associated things, this part fixed glycerol concentration of5%and the CaCl2concentration of2%, and then studied the three other key operating parameters, sodium alginate concentration, CMC concentration and CaCl2solution cross-linking time by Box-Behnken design and RSM analysis. The minimal WVP,0.3898g·mm/m2-h-kPa, was achieved under the optimum conditions, found to be algin concentration, CMC concentration, and CaCl2solution cross-linking time equal to8.04%,0.13%and12min, respectively. The predicted value was0.3974, and excellent correlation between predicted and measured values. The optimal conditions will provide an important reference for the manufacture of algin enteric hard capsule shell.2. The enteric hard capsule shell used algin as the main raw material. The method of two calcification was selected by experiments. The source, time, concentration, temperature of the first and the second calcification, the temperature and time of the first and the second drying conditions were studied. The single-factor tests were determined the best conditions:the source, time, concentration, temperature of the first calcification and the temperature and time of the first drying conditions were calcium gluconate,40℃,4min,4%,50℃and1h; the source, time, concentration, temperature of the second calcification and the temperature and time of the second drying conditions were calcium lactate,25℃,20min,6%,50℃and1.5h. Capsule shell obtained under this condition had good hardness, no fold and sunken on the top, and could take off shell from mold easily. And open up a new development path of plant enteric hard capsule shell.3. The release characteristics and the performances of self-made algin enteric hard capsule shell were studied.(1) The absorption spectrums of L-glutamine in a simulated gastric solution and simulated intestinal solution were determined, and the best measurement wavelength in the simulated gastric and simulated intestinal environments were285nm and264nm. Based on the best measurement wavelength, the precision, recovery rate and stability experiments in the simulated gastric and simulated intestinal environments were studied. In the simulated gastric and simulated intestinal environments, the RSD values of precision experiments were less than1.13%and1.54%; the recovery rate of recovery rate experiments were from99.81to100.19%, and99.91to100.23%, the RSD values of recovery rate experiments were less than0.7%and0.5%; the RSD value of stability experiment were less than1.17%and1.52%. In a simulated gastric environment, the release rate of self-made algin enteric hard capsule shell was0after2hours. In simulated intestinal environment, the release rate had reached70%at35min and92%at60min, could meet the pharmacopoeia standards.(2) The length, single-wall thickness, the outer diameter of the capsule shells could meet the standards of China Pharmaceutical Packaging Association. The performances of capsule shell were examined. Its appearance was glossed, and it had no obvious color difference, no cracks, no bubbles, no clip wrinkles, no different color points, no scratches, no wrinkles, no shreds, no powder leakage, no breaks, met the standards of China Pharmaceutical Packaging Association and Pharmacopoeia. In disintegration experiment, the capsule shell did not disintegrate in the simulated gastric environment, and disintegrated in simulated intestinal environments within2minutes and55seconds, met the standards of Pharmacopoeia. The value of loss on drying was10.98%, less than the standards of Pharmacopoeia, had more advantage than gelatin capsule shell; the value of ignition.residue was1.08%, met the standards of Pharmacopoeia; both of the.contents of heavy metals(lead), and chromium were0, met the pharmacopoeia standards; the value of bacterial total was10CFU/g, and mold, yeast, E. coli did not find, met the standards of Pharmacopoeia.