Study On Acid-hydrolyzed-hydroxypropylated Starch Applied To Hollow Hard Capsules

The active pharmaceutical ingredients can be delivered orally using hollow hard capsules,which have been widely used in the fields of pharmaceuticals,healthcare products,and food.Although the main raw material for preparation of hollow hard capsules on the market today is gelatin,there are some severe challenges and restrictions for the production and application of gelatin capsules,owing to the outbreak of poison capsules and the influence of cultural factors,such as vegetarianism and religious beliefs.Starch is green and renewable,making it be a widely available and biocompatible resource.Therefore,it has been a research hotspot in recent years to develop starch-based hollow hard capsules.The acid-hydrolyzed-hydroxypropylated potato starch?AHP?modified with varying hydrolysis time and propylene oxide content was prepared in this paper.Through the study on the rheological properties,gelation properties and starch film properties of AHP,the dual-modified starch,which met the requirements for making hollow hard capsules,was selected with comparison to the characteristics of gelatin.Then the starch-based hollow hard capsules with excellent properties were prepared after the optimization of gelling agents,plasticizers and preparation process.The main contents of this paper are as follows:Firstly,different AHP were prepared,and then the relationship between the degree of substitution and the physiochemical properties was investigated according to the requirements of traditional preparation process for hollow hard capsules.The results showed that any increase in the hydrolysis time or propylene oxide content resulted in an increase in the flow behavior index and a decrease in the viscosity of AHP.An improved gelation performance was observed with increasing acid hydrolysis.Particularly,the sample hydrolyzed for 5 h showed the best gelling properties.Through the study on the relative molecular mass distributions and the microstructure of the samples,it was found that the relative molecular mass distribution of the starch,which was hydrolyzed for 5 h and hydroxypropylated with 8%?w/w,based on the dry weight of the starch?of propylene oxide added,was relatively uniform and hydrophilic,resulting in a more uniform and dense gel network structure.Moreover,the relevant characteristics of starch films were also determined.It was indicated that the water-holding capacity and flexibility of the starch films were improved with increasing hydroxypropylation,whereas the acid hydrolysis made the mechanical strength of the films better.Through the examination of the solubility,mechanical properties and water-holding characteristics of the starch film,the reaction conditions for preparation of the starch-based capsule material were determined as follows:5 h of the acid hydrolysis time,and the amount of propylene oxide added was 8%?w/w?of the dry weight of starch.Secondly,the effects of gelling agents and plasticizers on the gelling properties and film properties of AHP,respectively,were investigated in this paper.The results showed that the gelation and film properties of AHP with KCl added were better than those with addition of Na₂SO₄,sodium citrate?SC?,and NaCl.In this paper,the synergistic effect of sodium dodecyl sulfate?SDS?and salts on the gelation properties of AHP was further explored using starch complexing ability and Zeta potential analyses.It was revealed that a similar structure to carrageenan was obtained resulted from SDS combining with amylose to form a complex.Therefore,the AHP aggregated with salt ions under the electrostatic interactions.Glycerol is a plasticizer for starch film.The mechanical and water-holding properties of the starch film were relatively poor with low content of glycerol added;whereas the mechanical strength of the film was significantly weakened,despite of improved film flexibility and water holding capacity,with content of glycerol increasing.In conclusion,superior gelation and film properties of AHP would be obtained on the condition that SDS and KCl were selected as the gelling additives and the concentration of SDS and KCl used were 0.24%?w/w?and 0.57%?w/w?,respectively.Finally,the concentration and the temperature of the glue during preparation process of starch based hollow hard capsules were optimized according to the indexes of disintegration time,tightness and friability.The results revealed that the viscosity and processing characteristics of the glue were directly affected by the glue concentration;and the surface temperature of the mold was related to the glue temperature during the dip-molding process,which in turn affected the thickness of the gel formed on the mold.Moreover,the viscosity of the glue,as well as the thickness,hardness,and disintegration time of hollow hard capsules were significantly influenced by the concentration and temperature of the glue.It was found that the tightness index of starch-based hollow hard capsules with a certain glue concentration,which was higher than 20%?w/w?,could meet the qualifications of China Pharmacopoeia Packaging Association;the disintegration time of starch-based hollow hard capsules was less than 10 min when the concentration of the glue was lower than 22%?w/w?or the temperature of the glue was higher than 55°C.Hence,the final preparation process parameters of hollow hard capsules were 22%?w/w?of glue concentration and 55°C of glue temperature.