Study On Electrosprayed Soft Capsules Of Millimeter-Size For Specifically Delivering Fish Oil/Nutrients To Stomach And Intestines

Fish oil is rich in omega-3 unsaturated fatty acids,which have the functions of regulating blood lipid,protecting the heart and protecting the brain,cleaning up blood clots and regulating blood pressure,preventing arteriosclerosis,strengthening the brain and improving memory,relieving eye strain,protecting eyesight,and enhancing immunity.It is an important nutrient substance for human being.However,Fish oil is fishy,poor water solubility,and unstable to light,heat,and oxygen like many other highly active nutrients due to the low chemical stability of the double bond,so not easy to store and transport,which largely restrain the wide applications in the food and pharmaceutical industries.Therefore,it is necessary to study its storage methods to make better use of fish oil/nutrients.Encapsulation is the most common method for storing highly active substances or substances containing highly active ingredients.In the pharmaceutical industry,capsules are often used to locate and deliver drugs to certain parts of the body.Contrasting to the traditional centimeter-sized capsules that difficult to swallow or micro/nanometer-sized capsules that suffer from limited loading capacity for fish oil/nutrients and lowered stability,the millimeter-sized capsules with good enough stability could be a potential solution in solving these problems.Electrostatic spray is an efficient and convenient technology for capsule preparation with low cost and high yield.This research topic focuses on fish oil and lipophilic nutrient?-carotene.Millimeter-size soft capsules with core-shell structure were prepared by electrospray technology,and their stability and positioning release were studied.The following work was carried out:?1?Electrosprayed core-shell millimeter-sized soft capsules were fabricated by a custom-designed coaxial electrospray instrument.Fish oils and sodium alginate solutions were used as core and shell materials,respectively.The millimeter-sized soft core-shell capsules of 0.42-1.85 mm with inner diameter of 0.36-1.75 mm.In order to prepare soft capsules with uniform particle size,distinct core and uniform shell thickness,a single factor experiment was designed.Soft capsule was prepared by changing the sodium alginate concentration and electrostatic spraying conditions,and its morphology and particle size were analyzed by digital camera,optical microscope,fluorescence microscope and scanning electron microscope.Typical electrosprayed core-shell millimeter-sized soft capsules were fabricated as below optimized conditions:Fish oils and sodium alginate solution?2%?were loaded in 5 m L syringes,which were connected to the inner needle?23#?and the outer needle?17#?,respectively,of the coaxial needles.An applied voltage of 20 k V was produced using a high voltage power supply.The feeding rates for the inner phase and the outer phase were 10 and 40?L/min.The distance between the coaxial needle and the liquid surface of the collecting solution was about 9 cm.The working temperature was 15–25?.The relative humidity was40%-50%.Coaxial needle movement speed was 100 mm/min.The receiving rod rotates at 100-120 RPM.The controller minus ratio was 27.S section was 113.00.25 m M Ca Cl₂solution was used as collecting solution.?2?After the fish oil soft capsule preparation parameters optimization.In order to explore the stability and potential release in stomach and intestine of the soft capsule.Collecting solution,simulated stomach solution?10 m L Na H₂PO₄,p H 2.0,adjusted with phosphoric acid?and simulated small intestine solution?8.4 m L Na₂HPO₄,1.6 m L Na H₂PO₄,p H 7.5?were prepared.Soft capsules were put into different solution in vials and then were incubated at different temperatures?4?,20?,and 37??.The vials were kept in a dark place.At designated time points,the glass vials with soft capsules were photoed by a digital camera and the soft capsules were taken out for diameter measurement and bearing test.Found in fish oil soft capsule in Ca Cl₂ solution storage to maintain its stability;The fish oil soft capsule loaded with?-carotene was stable in simulated stomach solution and was not easy to be destroyed.However,the resulting soft capsules became apparently weakened and mechanically destructive in simulated small intestine solution.And became totally destroyed in simulated small intestine solution in20 minutes if they were firstly treated in simulated stomach solution,but not in simulated stomach solution,which makes the millimeter-sized capsules useful as containers for specific delivery of fish oils and lipophilic nutrients to stomach and intestines.?3?In order to verify the potential of digestive release of the soft capsule in vivo,further animal experiments were designed.In this work,healthy New Zealand white rabbits were chosen to construct rabbit models with full or empty stomachs.The digestion and absorption status of the soft capsule in the stomach and intestines were determined by analyzing the rabbit anatomy and blood samples.The results showed that the soft capsules without pre-treatment swell and then were destroyed in the small intestine after the soft capsules were directly into the stomachs of rabbit model with empty stomach.Which for specific delivery of fish oils and lipophilic nutrients to intestines.The soft capsule with pre-treatment of PBS 30 minutes were destroyed in the stomach after the soft capsules were directly into the stomachs of rabbit model with full stomach.The soft capsule were destroyed by gastric peristalsis easily as it has been swollen in the simulated small intestine solution.Which for specific delivery of fish oils and lipophilic nutrients to stomachs.The results of rabbit blood samples showed that the practical bioavailability values were 96.73%and 91.31%for gastric targeting and intestinal targeting,respectively.All these results suggested that the millimeter-sized soft capsules are small intestine-specific and suitable as containers for delivering fish oil and lipophilic nutrients into small intestine with excellent bioavailability.In conclusion.Electrosprayed core-shell millimeter-sized soft capsules were fabricated by a custom-designed coaxial electrospray instrument.Fish oils and sodium alginate solutions were used as core and shell materials,respectively.it is meaningful to develop soft capsules of millimeter-size to eliminate the difficulty in swallowing compared with traditional soft capsules of centimeter size,and increase the loading capacities and stability of fish oil,nutrients and drugs compared with micro/nano capsules.The millimeter-sized capsules were useful as containers for specific delivery of fish oils and lipophilic nutrients to stomach and intestines with excellent in vivo bioavailability?>90%?.The whole fabrication approach is very facile with no complicated polymer modification and formulations involved,which endows the resulting soft capsules with broad application prospect in food and drug industries.