The acid-alkali titration method of determination of degree of substitution(DS) for starch acetates has been improved by using acetone as solvent instead of ethanol. The saponification time could be reduced from 48 h or 72 h(using ethanol as solvent) to 1 h with acetone as solvent, and the RSD also decreased. The method has advantages of rapidity and high accuracy.
Two types of floating pellets in stomach were prepared. The first one: floating alginate pellets containing ethylcellulose and clarithromycin (AE)were pellets with dispersed ethylcellulose in the alginate gel matrix. The second one:ethylcellulose microspheres containing clarithromycin (Em) were first prepared by the emulsion solvent diffusion method, and then alginate pellets containing ethylcellulose microspheres (AEm) were prepared. The effects of processing parameters on morphology, size distribution, drug loading, in vitro drug release profiles, in vitro floating property of pellets were investigated. The results showed that about 80% of drug incorporated in AE was released at 2 h, while AEm with moderate drug content had sustained drug release property. The accumulative drug-release percent of AEm in vitro at 6 h were 65.9%—78.8%, and AEm could float in acetate buffer solution for more than 8 h.
An intestinal bio-microreactor with potential application prospect as a drug delivery system was proposed and studied. It was designed to overcome the problems such as complexity of separation and purification, and subsequent high costs, which always exist in producing genetically engineered drugs. For example, the process of separation and purification can be omitted by oral administration of genetically engineered microbes entrapped in semi-permeable membrane of microcapsules. The microencapsulated cells can live, metabolize and secrete therapeutic proteins in intestinal tract. In this paper, Pichia pastoris GS115 was selected as the model microbe, alginate-chitosan (AC) microcapsules as the carrier, and the physicochemical performance of the intestinal bio-microreactor was studied. It was found that the encapsulation efficiency of living yeast cells during the preparation of microcapsules was about 80%. It was shown that all AC microcapsules with yeast cells were kept intact in simulated gastric solution and simulated intestinal solution, and the survival of microencapsulated cells in simulated gastrointestinal solutions was 200-times higher than that of free cells, which showed that AC microcapsules can protect the activity of yeast cells. Furthermore, when being orally administered in mice, AC microcapsules could go through stomach and adhere to the surface of small intestinal mucous membrane over 12 h. Therefore, it was concluded that AC microencapsulated yeast cells could be used as intestinal bio-microreactor to secret bio-drugs in vivo directly.
The development of non-injection route for protein drugs, especially oral administration, has been the main focus of controlled release of drugs. To overcome obstacles unsolved such as enzyme degradation and penetration barrier of intestinal epi- thelium, technologies using microspheres as carrier of protein drugs have been proven potential to realize oral administration. It has been demonstrated that microspheres can not only protect proteins, but also facilitate the penetration and absorption through Peyer’s patches when the size is smaller than 10 μm. Therefore, the objective of this paper is to prepare protein-loaded microspheres with size ≤ 10 μm. Electrostatic droplet generation technology was used with insulin and hemoglobin as drug models and so- dium alginate as microsphere material. By decreas- ing the surface tension of feed solution by adding surfactant, and improving electric field distribution by changing the shape of container and electrode for gelation solution, protein-loaded microspheres with mean size less than 10 μm were successfully pro- duced through needle with diameter of 400 μm. The microspheres showed good sphericity and narrow size distribution. The mean standard variance of size distribution was 1.61. The encapsulation efficiency of proteins was over 70%. Moreover, the significance analysis of factors influencing the size of protein loaded microspheres was carried out through or- thogonal experiments, which showed that output voltage (U), needle diameter (D) and the distance between needle tips to the surface of gelation solu- tion (δ ) influenced significantly the size of micro-spheres. Finally, the statistic analysis showed that when confidence level was α=0.05, and α=0.1, con- fidence interval of microsphere size can be (6.2545, 10.1735) and (6.6022, 9.8258) correspondingly, suggesting that there is good repeatability and reli- ability for improving electrostatic droplet generation technology to prepare protein-loaded microspheres with size ≤10 μm.
